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Sample records for administration significantly enhanced

  1. Enhanced bioavailability of opiates after intratracheal administration

    SciTech Connect

    Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

    1986-03-01

    Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities (codeine (84%), ethylmorphine (100%), and morphine (87%)) of drugs with poor oral availabilities were all markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability.

  2. Serotonergic mechanism underlying tranylcypromine enhancement of nicotine self-administration

    PubMed Central

    Villégier, Anne-Sophie; Belluzzi, James D.; Leslie, Frances M.

    2010-01-01

    Although nicotine is generally considered to be the main psychoactive component of tobacco, growing evidence highlights the importance of non-nicotine compounds in smoking reinforcement. Monoamine oxidase (MAO) inhibition is a major consequence of smoking and MAO inhibitors, such as tranylcypromine, increase nicotine reinforcement. Tranylcypromine has multiple pharmacological effects, increasing monoamine release for a few hours immediately after its administration and blocking MAO activity for several days. To assess the relative role of these two actions, adult male rats were tested in consecutive daily 3-hr sessions for self-administration of nicotine (3μg/kg/inj, i.v.) either 20 hr or 1hr following administration of tranylcypromine (3 mg/kg). Both paradigms were shown to produce highly significant inhibition of MAO activity. However, whereas animals readily acquired self-administration when pretreated with tranylcypromine 1hr prior to testing, they did not with the longer pretreatment interval. Such animals did immediately acquire nicotine self-administration when the tranylcypromine pretreatment interval was switched to 1hr prior to testing on day 4, indicating that an acute effect of the MAO inhibitor was responsible for enhanced nicotine reinforcement. Several lines of evidence implicate serotonin (5-HT) as the mediator of this enhancement: (1) Tranyclypromine-enhanced nicotine reinforcement was blocked by the 5-HT2 receptor antagonists, ritanserin and ketanserin; (2) parachloroamphetamine (PCA), a 5-HT releaser, also enhanced nicotine self-administration in animals in which MAO activity was inhibited; (3) pretreatment with tranylcypromine increased PCA-induced 5-HT overflow in the nucleus accumbens. These findings suggest that MAO inhibition enhances serotonergic transmission, which serves a critical role in the reinforcing effects of nicotine. PMID:20936688

  3. Intranasal midazolam administration enhances amnesic effect in rats.

    PubMed

    Kadono, Takao; Kawano, Takashi; Yamanaka, Daiki; Tateiwa, Hiroki; Urakawa, Manami; Locatelli, Fabricio M; Yokoyama, Masataka

    2016-06-01

    Intranasal (i.n.) administration of midazolam has been shown to be effective and safe for its sedative, anxiolytic, and anticonvulsant effects. However, there has been no investigation on the influence of i.n. administration on midazolam-induced anterograde amnesia. In addition, although the potential of direct drug delivery from the nose to the central nervous system (CNS) has recently become a topic of great interest, it remains unclear whether this pathway is also involved after i.n. midazolam. In this study, we examined the efficacy and the underlying mechanism of i.n. administration compared with intramuscular (i.m.) administration on midazolam-induced amnesia in rats. Equivalent doses of 0.6 mg/kg midazolam were administered via either the i.m or the i.n. route. Anterograde amnesia was assessed by a contextual/cued fear conditioning test. Each animal was conditioned 20 min after drug administration and then tested for a freezing response 24 h later. Midazolam administration by either route produced a similar level of light sedation (minimum spontaneous activity). However, i.n. administration of midazolam induced significantly less freezing behavior compared with i.m. midazolam. Furthermore, in rats with disrupted electrical input from the olfactory epithelium after an olfactotoxicant 3-methylindole administration, the i.n.-mediated enhanced amnesic effect of midazolam was not observed. Our findings indicate that i.n midazolam could probably generate olfactory signals to the brain via benzodiazepine receptors and, compared with i.m. administration, can produce a more significant amnesic effect without alteration in sedative levels. Further clinical studies are warranted. PMID:26943484

  4. Enhanced bioavailability after oral and pulmonary administration of baicalein nanocrystal.

    PubMed

    Zhang, Jianjun; Lv, Huixia; Jiang, Kun; Gao, Yuan

    2011-11-25

    The aim of the study was to investigate the potential of oral and pulmonary nanocrystal to enhance the bioavailability of baicalein, a bioactive flavonoid isolated from the root of Scutellaria baicalensis Georgi. So far, the nano-sized delivery system of baicalein and its pulmonary delivery have received no exploration. In the present investigation, the baicalein nanocrystal was prepared by anti-solvent recrystallization followed by high pressure homogenization. In vitro characterization was performed including particle size and distribution, Zeta potential, dissolution, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry. It was indicated that no crystalline change was observed after nanocrystal preparation. The baicalein nanocrystal containing only trace of stabilizer exhibited a significantly enhanced dissolution of baicalein. In vivo test was also carried out in rats and pharmacokinetic parameters of the baicalein crystal and the baicalein nanocrystal after gavage and pulmonary administration were compared, based on the simultaneous determination of baicalein and baicalin by high performance liquid chromatography. The mean relative bioavailability of oral baicalein nanocrystal was 1.67-fold that of oral baicalein crystal. The pulmonary baicalein nanocrystal had rapid and extensive absorption and had almost identical pharmacokinetic parameters to intravenous baicalein injection. PMID:21878378

  5. 21 CFR 10.70 - Documentation of significant decisions in administrative file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Documentation of significant decisions in administrative file. 10.70 Section 10.70 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... appropriate employees, and show all persons to whom copies were sent; (4) Avoid defamatory...

  6. Significant enhancement of photovoltage in artificially designed perovskite oxide structures

    NASA Astrophysics Data System (ADS)

    Zhou, Wen-jia; Jin, Kui-juan; Guo, Hai-zhong; He, Xu; He, Meng; Xu, Xiu-lai; Lu, Hui-bin; Yang, Guo-zhen

    2015-03-01

    La0.9Sr0.1MnO3/insulator/SrNb0.007Ti0.993O3 multilayer and La0.9Sr0.1MnO3/SrNb0.007Ti0.993O3/In2O3:SnO2(ITO)/La0.9Sr0.1MnO3/SrNb0.007Ti0.993O3 multilayer structures were designed to enhance the photovoltage. The photovoltages of these two structures under an illumination of 308 nm laser are 410 and 600 mV, respectively. The latter is 20 times larger than that (30 mV) observed in La0.9Sr0.1MnO3/SrNb0.007Ti0.993O3 single junction. The origin of such significant enhancement of photovoltage is discussed in this letter. These results suggest that the photoelectric property of perovskite oxides could be much improved by artificial structure designing. The enhanced photovoltaic effects have potential applications in the ultraviolet photodetection and solar cells.

  7. Nicotine administration enhances negative occasion setting in adolescent rats.

    PubMed

    Meyer, Heidi C; Chodakewitz, Molly I; Bucci, David J

    2016-04-01

    Substantial research has established that exposure to nicotine during adolescence can lead to long-term changes in neural circuitry and behavior. However, relatively few studies have considered the effects of nicotine use on cognition during this critical stage of brain development. This is significant because the influence of nicotine on cognitive performance during adolescence may contribute to the development of regular nicotine use. For example, improvements in cognitive functioning may increase the perceived value of smoking and facilitate impulses to smoke. To address this, the present research tested the effects of nicotine on a form of inhibitory learning during adolescence. Specifically, adolescent rats were exposed to nicotine as they were trained in a negative occasion setting paradigm, in which successful performance depends on learning the conditions under which it is, or is not, appropriate to respond to a target stimulus. Here, we found that nicotine administration enhances negative occasion setting in adolescents. In addition, nicotine increased the amount of orienting behavior directed toward the inhibitory stimulus, suggesting that improvements in this form of behavioral inhibition may be attributed to nicotine-induced increases in attentional processing. These results may help elucidate the factors that contribute to the onset as well as continued use of products containing nicotine during adolescence and provide insight to increase the effectiveness of interventions targeted at reducing the prevalence of adolescent smoking. PMID:26779671

  8. A Hybrid Actuation System Demonstrating Significantly Enhanced Electromechanical Performance

    NASA Technical Reports Server (NTRS)

    Su, Ji; Xu, Tian-Bing; Zhang, Shujun; Shrout, Thomas R.; Zhang, Qiming

    2004-01-01

    A hybrid actuation system (HYBAS) utilizing advantages of a combination of electromechanical responses of an electroactive polymer (EAP), an electrostrictive copolymer, and an electroactive ceramic single crystal, PZN-PT single crystal, has been developed. The system employs the contribution of the actuation elements cooperatively and exhibits a significantly enhanced electromechanical performance compared to the performances of the device made of each constituting material, the electroactive polymer or the ceramic single crystal, individually. The theoretical modeling of the performances of the HYBAS is in good agreement with experimental observation. The consistence between the theoretical modeling and experimental test make the design concept an effective route for the development of high performance actuating devices for many applications. The theoretical modeling, fabrication of the HYBAS and the initial experimental results will be presented and discussed.

  9. Protopanaxadiol, an Active Ginseng Metabolite, Significantly Enhances the Effects of Fluorouracil on Colon Cancer

    PubMed Central

    Wang, Chong-Zhi; Zhang, Zhiyu; Wan, Jin-Yi; Zhang, Chun-Feng; Anderson, Samantha; He, Xin; Yu, Chunhao; He, Tong-Chuan; Qi, Lian-Wen; Yuan, Chun-Su

    2015-01-01

    In this study, we evaluated the effects of protopanaxadiol (PPD), a gut microbiome induced ginseng metabolite, in increasing the anticancer effects of a chemotherapeutic agent fluorouracil (5-FU) on colorectal cancer. An in vitro HCT-116 colorectal cancer cell proliferation test was conducted to observe the effects of PPD, 5-FU and their co-administration and the related mechanisms of action. Then, an in vivo xenografted athymic mouse model was used to confirm the in vitro data. Our results showed that the human gut microbiome converted ginsenoside compound K to PPD as a metabolite. PPD and 5-FU significantly inhibited HCT-116 cell proliferation in a concentration-dependent manner (both p < 0.01), and the effects of 5-FU were very significantly enhanced by combined treatment with PPD (p < 0.01). Cell cycle evaluation demonstrated that 5-FU markedly induced the cancer cell S phase arrest, while PPD increased arrest in G1 phase. Compared to the control, 5-FU and PPD increased apoptosis, and their co-administration significantly increased the number of apoptotic cells (p < 0.01). Using bioluminescence imaging, in vivo data revealed that 5-FU significantly reduced the tumor growth up to Day 20 (p < 0.05). PPD and 5-FU co-administration very significantly reduced the tumor size in a dose-related manner (p < 0.01 compared to the 5-FU alone). The quantification of the tumor size and weight changes for 43 days supported the in vivo imaging data. Our results demonstrated that the co-administration of PPD and 5-FU significantly inhibited the tumor growth, indicating that PPD significantly enhanced the anticancer action of 5-FU, a commonly used chemotherapeutic agent. PPD may have a clinical value in 5-FU’s cancer therapeutics. PMID:25625815

  10. Porcine JAB1 significantly enhances apoptosis induced by staurosporine

    PubMed Central

    Jiang, P; Wang, J; Kang, Z; Li, D; Zhang, D

    2013-01-01

    c-Jun activation domain-binding protein-1 (JAB1), also known as the subunit 5 of the COP9 signalosome, is a multifunctional protein that regulates cell proliferation, apoptosis and oncogenesis by interacting with and subsequently degrading a large number of proteins. Although human JAB1 (hJAB1) has been studied for a long time, studies on porcine JAB1 (pJAB1) have never been reported. In the present study, we cloned and characterized the pJAB1 gene. The genomic structure of the pJAB1 gene was determined. The open-reading frame of pJAB1 encoded 334 amino acids. The deduced amino acid sequence was highly similar to homologs in other species. Furthermore, the tertiary structure analysis and phylogenetic analysis indicated that JAB1 was highly conservative among species. pJAB1 may interact with several proteins according to protein–protein interactions analysis. In addition, pJAB1 was found to be universally expressed in porcine tissues. Subcellular localization analysis showed that GFP–pJAB1 fusion protein distributed specifically in the cytoplasm. Flow cytometric analysis proved that pJAB1 significantly enhanced apoptosis induced by staurosporine, which at least partially depended on the activation of caspase-9 and caspase-3. This study is useful for understanding the function of pJAB1 and offers a potential molecular model for the investigation of diseases related to hJAB1. PMID:24091666

  11. Microperforations Significantly Enhance Diffusion Across Round Window Membrane

    PubMed Central

    Kelso, Catherine M.; Watanabe, Hirobumi; Wazen, Joseph M.; Bucher, Tizian; Qian, Zhen J.; Olson, Elizabeth S.; Kysar, Jeffrey W.; Lalwani, Anil K.

    2014-01-01

    Hypothesis Introduction of microperforations in round window membrane (RWM) will allow reliable and predictable intracochlear delivery of pharmaceutical, molecular or cellular therapeutic agents. Background Reliable delivery of medications into the inner ear remains a formidable challenge. The RWM is an attractive target for intracochlear delivery. However, simple diffusion across intact RWM is limited by what material can be delivered, size of material to be delivered, difficulty with precise dosing, timing, and precision of delivery over time. Further, absence of reliable methods for measuring diffusion across RWM in vitro is a significant experimental impediment. Methods A novel model for measuring diffusion across guinea pig RWM, with and without microperforation, was developed and tested: cochleae, sparing the RWM, were embedded in 3D-printed acrylic holders using hybrid dental composite and light cured to adapt the round window niche to 3ml Franz diffusion cells. Perforations were created with 12.5μm diameter needles and examined with light microscopy. Diffusion of 1mM Rhodamine B across RWM in static diffusion cells was measured via fluorescence microscopy. Results The diffusion cell apparatus provided reliable and replicable measurements of diffusion across RWM. The permeability of Rhodamine B across intact RWM was 5.1 × 10-9 m/s. Manual application of microperforation with a 12.5μm diameter tip produced an elliptical tear removing 0.22±0.07% of the membrane and was associated with a 35x enhancement in diffusion (p<0.05). Conclusion Diffusion cells can be applied to the study of RWM permeability in vitro. Microperforation in RWM is an effective means of increasing diffusion across the RWM. PMID:25310125

  12. Method of Administration of PROMIS Scales Did Not Significantly Impact Score Level, Reliability or Validity

    PubMed Central

    Bjorner, Jakob B.; Rose, Matthias; Gandek, Barbara; Stone, Arthur A.; Junghaenel, Doerte U.; Ware, John E.

    2014-01-01

    Objective To test the impact of method of administration (MOA) on score level, reliability, and validity of scales developed in the Patient Reported Outcomes Measurement Information System (PROMIS). Study Design and Setting Two non-overlapping parallel forms each containing 8 items from each of three PROMIS item banks (Physical Function, Fatigue and Depression) were completed by 923 adults with COPD, depression, or rheumatoid arthritis. In a randomized cross-over design, subjects answered one form by interactive voice response (IVR) technology, paper questionnaire (PQ), personal digital assistant (PDA), or personal computer (PC) and a second form by PC, in the same administration. Method equivalence was evaluated through analyses of difference scores, intraclass correlations (ICC), and convergent/discriminant validity. Results In difference score analyses, no significant mode differences were found and all confidence intervals were within the pre-specified MID of 0.2 SD. Parallel forms reliabilities were very high (ICC=0.85-0.93). Only one across mode ICC was significantly lower than the same mode ICC. Tests of validity showed no differential effect by MOA. Participants preferred screen interface over PQ and IVR. Conclusion We found no statistically or clinically significant differences in score levels or psychometric properties of IVR, PQ or PDA administration as compared to PC. PMID:24262772

  13. Phase Behavior and Significantly Enhanced Toughness in Polylactide Graft Copolymers

    NASA Astrophysics Data System (ADS)

    Robertson, Megan; Theryo, Grayce; Jing, Feng; Hillmyer, Marc

    2011-03-01

    Polylactide (PLA), a biodegradable polyester derived from plant sugars, is commercially available and used in a variety of applications ranging from serviceware to resorbable sutures. One limitation to diversifying the applications of the material is its inherent brittleness. Graft copolymers containing PLA arms and a rubbery aliphatic polymer backbone were synthesized by a combination of ring-opening metathesis and ring-opening transesterification polymerizations. The high degree of incompatibility between the arms and backbone resulted in microphase separation of the graft copolymer at increasingly low fractions of the backbone polymer, as evidenced by small-angle x-ray scattering. In graft copolymers with a rubbery content of only 5 wt percent, the tensile strain at break was observed to be as high as twenty times that of neat PLA. Studies are underway to provide insight into the critical polymer molecular parameters for enhanced toughness and the deformation mechanisms.

  14. Annual committee reports on significant legislative, judicial, and administrative developments in 1981: Water-Quality committee

    SciTech Connect

    Not Available

    1982-01-01

    This review of 1981 developments is divided into four basic parts. The first covers legislative, judicial, and administrative developments under the Clean Water Act (CWA); the second covers judicial and administrative developments under the Safe Drinking Water Act (SDWA); the third covers judicial developments respecting private rights of action and the federal common law of nuisance. 109 references.

  15. Annual committee report on significant legislative, judicial, and administrative developments in 1980: Water Quality Committee

    SciTech Connect

    Not Available

    1981-01-01

    This review of 1980 developments is divided into three parts. The first covers judicial and administrative developments under the Clean Water Act (CWA) such as industrial guidelines and standards; the second covers judicial administrative and legislative developments under the Safe Drinking Water Act (SDWA); and the third covers judicial developments in the areas of private rights of action and the federal common law of nuisance. 320 references.

  16. Development of Program for Enhancing the Ideal Desirable Characteristic of Basic School Administrators

    ERIC Educational Resources Information Center

    Khakhlong, Chettha; Julsuwan, Suwat; Somprach, Kanokorn; Khangpheng, Samrit

    2015-01-01

    The objective of this research is to develop a program for enhancing ideal desirable characteristic of basic school administrators. An in-depth interview was done with experts. The opinions of school administrators, assistant school administrators, and teachers as the chiefs of academic work were found out. A total of 330 persons participated in…

  17. Enhancing the Interpretation of "Significant" Findings: The Role of Mixed Methods Research

    ERIC Educational Resources Information Center

    Onwuegbuzie, Anthony J.; Leech, Nancy L.

    2004-01-01

    The present essay outlines how mixed methods research can be used to enhance the interpretation of significant findings. First, we define what we mean by significance in educational evaluation research. With regard to quantitative-based research, we define the four types of significance: statistical significance, practical significance, clinical…

  18. Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans.

    PubMed

    Tamboli, Robyn A; Sidani, Reem M; Garcia, Anna E; Antoun, Joseph; Isbell, James M; Albaugh, Vance L; Abumrad, Naji N

    2016-07-01

    Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These "isoglycemic clamps" enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion. PMID:27279247

  19. Annual committee reports on significant legislative, judicial, and administrative developments in 1982: Environmental Quality Committee

    SciTech Connect

    Not Available

    1983-01-01

    Judicial developments during 1982 dominated activities involving the National Environmental Policy Act (NEPA), the Federal Insecticide, Fungicide and Rotenticide Act, and Marine Sanctuaries, with some changes in administrative procedures and no legislative developments. The Endangered Species Act was amended to expedite changes to the lists and to alter exemption and international trade requirements. Several lawsuits challenged review standards and litigation claims. 231 references. (DCK)

  20. Enhancing Effective Administration at Faculty Level through Shared Leadership

    ERIC Educational Resources Information Center

    Afful, Deborah

    2015-01-01

    We live in the world of knowledge, and knowledge keeps increasing in shape and complexity. As a result, no single individual has the repository of knowledge required to effectively manage an organisation all alone to affect organisational performance positively. This explains why administration is explained as doing things through the efforts of…

  1. Skills Enhancement Program. Performance Report, Evaluation Report, and Administration Manual.

    ERIC Educational Resources Information Center

    Wayne County Community Coll., Detroit, MI.

    This document contains three products of the Skills Enhancement Program, a cooperative venture between Industrial Technology Institute (ITI), Wayne County (Michigan) Community College (WCCC), and Great Lakes Steel (GLS). The performance report describes the project's objective of designing a job-related literacy curriculum for hourly workers and…

  2. Enhancing marketing recruitment strategies: administrator tenure and nursing expenditures.

    PubMed

    Gunby, Norris White

    2005-01-01

    When recruiting nurses, long-term care facilities require an ability to identify salient organizational characteristics that are attractive to potential nursing services candidates vis-à-vis their competitors. The findings of this study suggest that information on administrative tenure can be utilized to attract applicants by appealing to criteria within their high-involvement job search activities. High-involvement applicants proactively seek recruitment content that provides essential job attributes that match their needs and skills and are more apt to be a higher quality candidate. Based upon the study's findings, managers are offered marketing strategy recommendations for tailoring recruiting messages that appeal to high-involvement job seekers. PMID:17182460

  3. Investing in Administrator Efficacy: An Examination of Professional Development as a Tool for Enhancing Principal Effectiveness

    ERIC Educational Resources Information Center

    Grissom, Jason A.; Harrington, James R.

    2010-01-01

    A primary goal of school districts' investments in professional development for principals is to enhance their effectiveness. This study examines the connection between administrator professional development and performance in a national sample of schools. We show that not all types of administrator professional development participation correlate…

  4. Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.

    PubMed

    Cannady, Reginald; Fisher, Kristen R; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W

    2013-01-01

    Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA) receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol-reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pre-treated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pre-treatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pre-treatment did not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7-dinitroquinoxaline-2,3-dione (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pre-treatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle-treated P-rats. These data suggest that enhanced glutamate activity at AMPA

  5. N-acetylaspartylglutamate (NAAG) inhibits intravenous cocaine self-administration and cocaine-enhanced brain-stimulation reward in rats.

    PubMed

    Xi, Zheng-Xiong; Kiyatkin, Michael; Li, Xia; Peng, Xiao-Qing; Wiggins, Armina; Spiller, Krista; Li, Jie; Gardner, Eliot L

    2010-01-01

    Pharmacological activation of group II metabotropic glutamate (mGlu2 and mGlu3) receptors inhibits reward-seeking behavior and/or rewarding efficacy induced by drugs (cocaine, nicotine) or natural rewards (food, sucrose). In the present study, we investigated whether elevation of brain N-acetylaspartylglutamate (NAAG), an endogenous group II mGlu receptor agonist, by the NAAG peptidase inhibitor 2-PMPA attenuates cocaine's rewarding effects, as assessed by intravenous cocaine self-administration and intracranial electrical brain-stimulation reward (BSR) in rats. Systemic administration of 2-PMPA (10, 30, 100 mg/kg, i.p.) or intranasal administration of NAAG (100, 300 microg/10 microl/nostril) significantly inhibited intravenous cocaine self-administration under progressive-ratio (PR), but not under fixed-ratio 2 (FR2), reinforcement conditions. In addition, 2-PMPA (1, 10, 30 mg/kg, i.p) or NAAG (50, 100 microg/10 microl/nostril) significantly inhibited cocaine-enhanced BSR, but not basal BSR. Pretreatment with LY341495 (1 mg/kg, i.p.), a selective mGlu2/3 receptor antagonist, prevented the inhibitory effects produced by 2-PMPA or NAAG in both the self-administration and BSR paradigms. In vivo microdialysis demonstrated that 2-PMPA (10, 30, 100 mg/kg) dose-dependently attenuated cocaine-enhanced extracellular dopamine (DA) in the nucleus accumbens (NAc). 2-PMPA alone inhibited basal NAc DA release, an effect that was prevented by LY341495. These findings suggest that systemic administration of 2-PMPA or intranasal administration of NAAG inhibits cocaine's rewarding efficacy and cocaine-enhanced NAc DA - likely by activation of presynaptic mGlu2/3 receptors in the NAc. These data suggest a potential utility for 2-PMPA or NAAG in the treatment of cocaine addiction. PMID:19559037

  6. Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

    NASA Astrophysics Data System (ADS)

    Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

    1999-03-01

    We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

  7. mGluR5 Positive Allosteric Modulation Enhances Extinction Learning Following Cocaine Self-Administration

    PubMed Central

    Cleva, Richard M.; Hicks, Megan P.; Gass, Justin T.; Wischerath, Kelly C.; Plasters, Elizabeth T.; Widholm, John J.; Olive, M. Foster

    2011-01-01

    Extinction of classically and instrumentally conditioned behaviors, such as conditioned fear and drug-seeking behavior, is a process of active learning, and recent studies indicate that potentiation of glutamatergic transmission facilitates extinction learning. In this study we investigated the effects of the type 5 metabotropic glutamate receptors (mGluR5) positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction of cocaine-seeking behavior in rats with a history of intravenous cocaine self-administration. To assess its effects on acquisition and consolidation of extinction learning, CDPPB (60 mg/kg) or vehicle was administered either 20 min prior to, or immediately following, each of 10 extinction sessions, respectively. When administered prior to each extinction session, CDPPB produced a significant reduction in the number of active lever presses on all 10 days of extinction training as compared to vehicle-treated animals. When administered following each extinction session, a significant reduction in the number of active lever presses was observed on the 2nd through 10th day of extinction. Both treatment regimens also reduced the number of extinction training sessions required to meet extinction criteria. Pre- or post-extinction training administration of CDPPB did not alter responding on the inactive lever and had no effects on open field locomotor activity. These data indicate that positive allosteric modulation of mGluR5 receptors facilitates the acquisition and consolidation of extinction learning following cocaine self-administration, and may provide a novel pharmacological approach to enhancing extinction learning when combined with cue exposure therapy for the treatment of cocaine addiction. PMID:21319882

  8. Systemic administration of rhIGF-I enhanced regeneration after sciatic nerve crush in mice.

    PubMed

    Contreras, P C; Steffler, C; Yu, E; Callison, K; Stong, D; Vaught, J L

    1995-09-01

    Despite numerous reports suggesting that insulin-like growth factor-I (IGF-I) may be involved in the survival and regeneration of damaged neurons in vitro and after local administration in vivo, there have been few studies on the effect of IGF-I administered systemically on regeneration of damaged nerves in vivo and the functional consequences of enhanced regeneration. In an earlier study, recombinant human IGF-I (rhIGF-I) administered systemically enhanced the rate of regeneration after a sciatic crush as measured by the number of nerve fibers/muscle section. The purpose of this study was to follow up this finding by evaluating whether rhIGF-I administered peripherally enhances the rate of functional recovery. In this study following nerve injury, mice lost the ability to grip a wire screen with their hind paws and to walk normally as indicated by a decrease in toe spread, internal toe spread and an increase in the angle between hind feet. The ability of injured mice treated with rhIGF-I to grip an inverted screen returned to control levels significantly faster than that of vehicle-treated mice (day 12 vs. day 15, respectively). Similarly, rhIGF-I treatment of injured mice resulted in toe spread, internal toe spread and angle values that were significantly better than that of vehicle-treated mice and returned to control levels faster than vehicle-treated injured mice. There was a parallel loss of innervation after sciatic nerve crush as measured by a loss in choline acetyltransferase activity in the soleus and gastrocnemius muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7562520

  9. Enhanced methamphetamine self-administration in a neurodevelopmental rat model of schizophrenia

    PubMed Central

    McCallum, Sarah E.; Glick, Stanley D.; O’Donnell, Patricio

    2008-01-01

    Rationale Substance abuse is more prevalent among patients with schizophrenia than in the general population. The considerable overlap in neurobiological disruptions thought to underlie each condition suggests that addictive behavior may represent a primary symptom of schizophrenia. Objective This study investigated drug-seeking in a neurodevelopmental animal model of schizophrenia, the neonatal ventral hippocampal lesion (NVHL) model. Materials and methods At postnatal day 7, rats received an excitotoxic ventral hippocampus lesion or a sham procedure and were trained as adults to self-administer methamphetamine (0.1 mg/kg/infusion) or respond for natural reinforcement (water or food). Results NVHL rats were faster than shams to acquire the operant response for either drug self-administration or water reinforcement, suggesting that simple instrumental learning may be enhanced in these animals. NVHL and sham rats displayed no differences in fixed-ratio (FR) responding for either methamphetamine or food, and both groups of animals were equally sensitive to methamphetamine dose changes (0.05, 0.1, or 0.2 mg/kg/infusion). However, under a progressive-ratio (PR) schedule, NVHL animals reached significantly higher break points (NVHL 18 infusions; sham 12 infusions) for methamphetamine but not food reinforcement, suggesting enhanced motivation to acquire drug and/or elevated incentive value of the drug that did not generalize to another form of reinforcement. Conclusions These data indicate that developmental disruption of the hippocampus elevates rats’ vulnerability to drug-seeking behavior under PR conditions. Furthermore, drug self-administration in the NVHL animal emulates addictive behavior in schizophrenia, making this model useful for investigating the mechanisms of dual diagnosis, including the neurobiological and behavioral similarities between addiction and schizophrenia. PMID:18500636

  10. Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

    PubMed

    De Britto, R L; Vanamail, P; Sankari, T; Vijayalakshmi, G; Das, L K; Pani, S P

    2015-06-01

    Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653). PMID:26691247

  11. Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

    PubMed Central

    Miura, Yuichiro; Payne, Matthew S.; Jobe, Alan H.; Kallapur, Suhas G.; Saito, Masatoshi; Stock, Sarah J.; Spiller, O. Brad; Ireland, Demelza J.; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A.; Newnham, John P.

    2014-01-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  12. Maternal intravenous administration of azithromycin results in significant fetal uptake in a sheep model of second trimester pregnancy.

    PubMed

    Kemp, Matthew W; Miura, Yuichiro; Payne, Matthew S; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Stock, Sarah J; Spiller, O Brad; Ireland, Demelza J; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A; Newnham, John P

    2014-11-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  13. Intranasal administration of glial-derived neurotrophic factor (GDNF) rapidly and significantly increases whole-brain GDNF level in rats.

    PubMed

    Bender, T S; Migliore, M M; Campbell, R B; John Gatley, S; Waszczak, B L

    2015-09-10

    Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) exerts significant neuroprotective effects on substantia nigra (SN) neurons in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). In this study we used enzyme-linked immunosorbent assay (ELISA) to determine GDNF brain levels and distribution to target regions (i.e. striatum and SN) following intranasal administration of GDNF at different time points after administration. Brain levels increased significantly within 1h following a single 50-μg dose of GDNF in a liposomal formulation, returning to baseline by 24h. In a second study, different doses of GDNF (10-150 μg) in phosphate-buffered saline (PBS) were studied at the 1-h time point. Dose-dependent increases in brain GDNF levels were observed with apparent saturation of uptake at doses above 100 μg. Liposomes delivered 10-fold more GDNF to brain than PBS despite yielding similar neuroprotective efficacy in the 6-OHDA model, suggesting incomplete release of GDNF from liposomes in tissue. In a third study, autoradiography was performed on brain sections taken 1h after intranasal (125)I-labeled GDNF. Radioactivity was detected throughout the brain along the rostral-to-caudal axis, indicating that nasally administered GDNF can reach target areas. Collectively, these results demonstrate that intranasal administration of GDNF in liposomes or PBS achieves significant increases in GDNF in target brain areas, supporting use of intranasal administration as a non-invasive means of delivering GDNF to the brain to protect dopamine neurons and arrest disease progression in PD. PMID:26166725

  14. A novel nanoscale organic-inorganic hybrid system with significantly enhanced AIE in aqueous media.

    PubMed

    Zheng, Tingting; Xu, Jia-Long; Wang, Xiao-Jun; Zhang, Jian; Jiao, Xiuling; Wang, Ting; Chen, Dairong

    2016-05-25

    We report the design and fluorescence properties of a novel aggregation-induced emission (AIE) system obtained by grafting carboxyl group conjugated AIE molecules onto monodispersed colloidal GaOOH nanocubes. Compared with nanoaggregates formed in mixed solvents, as-formed nanohybrids avoid contact with a "good" solvent, restrict the molecular motions more efficiently and show a significantly enhanced AIE. PMID:27147199

  15. Enhanced antitumor activity of low-dose continuous administration schedules of topotecan in prostate cancer

    PubMed Central

    Aljuffali, Ibrahim A; Mock, Jason N; Costyn, Leah J; Nguyen, Ha; Nagy, Tamas; Cummings, Brian S

    2011-01-01

    Purpose The objective of this study was to determine the antitumor effects of alternate dosing schedules of topotecan in prostate cancer. Results A concentration-dependent increase in cytotoxicity was observed in PC-3 and LNCaP cells after topotecan treatment using conventional and metronomic protocols. A significant increase in potency (2.4–18 fold, after 72 h) was observed following metronomic dosing compared with conventional dosing administration in both cell lines. Metronomic dosing also increased the percentage of PC-3 cells in the G2/M, compared with control, but did not alter LNCaP cell cycle distribution. Metronomic dosing increased p21 protein expression in LNCaP and PC-3 cells compared with conventional dosing. The observed in vitro activity was confirmed using an in vivo model of human prostate cancer. Metronomic dosing and continuous infusion decreased tumor volume significantly (p ≤ 0.05) compared with control and conventional topotecan treatment, but had no effect on tumor vascular staining. Methods The cytotoxicity of topotecan after conventional or metronomic dosing was determined by examining cellular morphology, mitochondrial enzymatic activity (MTT), total cellular protein (SRB), annexin V and propidium iodine (PI) staining, cell cycle and protein gel blot analysis in human prostate cancer cell lines (PC-3 and LNCaP) and the effects metronomic or continuous infusion on tumor growth in an in vivo tumor xenograft model. Conclusions These data support the hypothesis that low-dose continuous administration of topotecan increases potency compared with conventional dosing in prostate cancer. These data also suggest the novel finding that the enhanced antitumor activity of topotecan following low-dose exposure correlates to alterations in cell cycle and increased p21 expression. PMID:21709443

  16. Enhancing Administrators' Capacity for Leadership by Improving Evaluation Practices and Processes Project

    ERIC Educational Resources Information Center

    Mathes, Staci M.

    2009-01-01

    This problem-based learning project focused on the need to enhance the capacity for leadership of building administrators in order to effectively evaluate teachers. Federal and state guidelines mandate highly qualified teachers in every classroom, and teacher evaluation is an important component to ensure qualified teachers are in the classroom.…

  17. Enhancing Lyme Disease Surveillance by Using Administrative Claims Data, Tennessee, USA

    PubMed Central

    Jones, Stephen G.; Dunn, John R.; Schaffner, William; Jones, Timothy F.

    2015-01-01

    Lyme disease is underreported in the United States. We used insurance administrative claims data to determine the value of such data in enhancing case ascertainment in Tennessee during January 2011–June 2013. Although we identified ≈20% more cases of Lyme disease (5/year), the method was resource intensive and not sustainable in this low-incidence state. PMID:26291336

  18. Nucleotide Analog Prodrug, Tenofovir Disoproxil, Enhances Lymphoid Cell Loading Following Oral Administration in Monkeys

    PubMed Central

    Durand-Gasselin, Lucie; Van Rompay, Koen K.A.; Vela, Jennifer E.; Henne, Ilana N.; Lee, William A.; Rhodes, Gerry R.; Ray, Adrian S.

    2009-01-01

    The antiviral drug tenofovir (TFV) is orally administered as the fumarate salt of its disoproxil prodrug (TFV disoproxil fumarate (TDF)). TFV is a di-anion at physiological pH and, as a result, has poor lipid membrane permeability. Administration of the lipophilic and cell permeable prodrug, TFV disoproxil, enhances the oral absorption of TFV. In order to determine if oral administration of TDF also increases distribution to sites of viral infection, the plasma and circulating lymphoid cell pharmacokinetics of TFV and its phosphorylated metabolites were assessed following a single oral TDF or subcutaneous TFV administration at doses yielding equivalent plasma exposures to TFV in macaques. Despite TFV disoproxil’s lack of plasma stability and undetectable levels in the first plasma samples taken, oral administration of TDF resulted in 7.9-fold higher peripheral blood mononuclear cell exposures to the active metabolite, TFV-diphosphate. The apparent plasma terminal half-life (t1/2) of TFV was also longer following oral TDF relative to subcutaneous TFV administration (median t1/2 of 15.3 and 3.9 h, respectively), suggesting broader distribution to cells and tissues outside of the central plasma compartment. In conclusion, the disoproxil pro-moiety not only enhances the oral absorption of TFV but also tissue and lymphoid cell loading. These results illustrate that administration of even a fleeting prodrug can increase target tissue loading and gives valuable insight for future prodrug development. PMID:19545170

  19. Significant light absorption enhancement in silicon thin film tandem solar cells with metallic nanoparticles

    NASA Astrophysics Data System (ADS)

    Cai, Boyuan; Li, Xiangping; Zhang, Yinan; Jia, Baohua

    2016-05-01

    Enhancing the light absorption in microcrystalline silicon bottom cell of a silicon-based tandem solar cell for photocurrent matching holds the key to achieving the overall solar cell performance breakthroughs. Here, we present a concept for significantly improving the absorption of both subcells simultaneously by simply applying tailored metallic nanoparticles both on the top and at the rear surfaces of the solar cells. Significant light absorption enhancement as large as 56% has been achieved in the bottom subcells. More importantly the thickness of the microcrystalline layer can be reduced by 57% without compromising the optical performance of the tandem solar cell, providing a cost-effective strategy for high performance tandem solar cells.

  20. Significant light absorption enhancement in silicon thin film tandem solar cells with metallic nanoparticles.

    PubMed

    Cai, Boyuan; Li, Xiangping; Zhang, Yinan; Jia, Baohua

    2016-05-13

    Enhancing the light absorption in microcrystalline silicon bottom cell of a silicon-based tandem solar cell for photocurrent matching holds the key to achieving the overall solar cell performance breakthroughs. Here, we present a concept for significantly improving the absorption of both subcells simultaneously by simply applying tailored metallic nanoparticles both on the top and at the rear surfaces of the solar cells. Significant light absorption enhancement as large as 56% has been achieved in the bottom subcells. More importantly the thickness of the microcrystalline layer can be reduced by 57% without compromising the optical performance of the tandem solar cell, providing a cost-effective strategy for high performance tandem solar cells. PMID:27040376

  1. Enhanced bone morphogenetic protein-2-induced ectopic and orthotopic bone formation by intermittent parathyroid hormone (1-34) administration.

    PubMed

    Kempen, Diederik H R; Lu, Lichun; Hefferan, Theresa E; Creemers, Laura B; Heijink, Andras; Maran, Avudaiappan; Dhert, Wouter J A; Yaszemski, Michael J

    2010-12-01

    Bone morphogenetic proteins (BMPs) play a central role in local bone regeneration strategies, whereas the anabolic features of parathyroid hormone (PTH) are particularly appealing for the systemic treatment of generalized bone loss. The aim of the current study was to investigate whether local BMP-2-induced bone regeneration could be enhanced by systemic administration of PTH (1-34). Empty or BMP-2-loaded poly(lactic-co glycolic acid)/poly(propylene fumarate)/gelatin composites were implanted subcutaneously and in femoral defects in rats (n = 9). For the orthotopic site, empty defects were also tested. Each of the conditions was investigated in combination with daily administered subcutaneous PTH (1-34) injections in the neck. After 8 weeks of implantation, bone mineral density (BMD) and bone volume were analyzed using microcomputed tomography and histology. Ectopic bone formation and almost complete healing of the femoral defect were only seen in rats that received BMP-2-loaded composites. Additional treatment of the rats with PTH (1-34) resulted in significantly (p < 0.05) enhanced BMD and bone volume in the BMP-2 composites at both implantation sites. Despite its effect on BMD in the humerus and vertebra, PTH (1-34) treatment had no significant effect on BMD and bone volume in the empty femoral defects and the ectopically or orthotopically implanted empty composites. Histological analysis showed that the newly formed bone had a normal woven and trabecular appearance. Overall, this study suggests that intermittent administration of a low PTH dose alone has limited potential to enhance local bone regeneration in a critical-sized defect in rats. However, when combined with local BMP-2-releasing scaffolds, PTH administration significantly enhanced osteogenesis in both ectopic and orthotopic sites. PMID:20666615

  2. Co-administration of antigen with chemokine MCP-3 or MDC/CCL22 enhances DNA vaccine potency.

    PubMed

    Xie, Xinmei; Wang, Lin; Yang, Wenliang; Yu, Ruishuang; Li, Qingli; Pang, Xiaobin

    2015-08-01

    We evaluated the utility of chemokine MCP-3 and MDC/CCL22 as molecular adjuvants of DNA vaccines for botulinum neurotoxin serotype A (BoNT/A) in a Balb/c mouse model. Notably, the immunogenicity of the DNA vaccine against BoNT/A was not enhanced using a fusion of the AHc-C antigen with the MCP-3 or MDC/CCL22. Nevertheless, the potency of the DNA vaccine was significantly modulated and enhanced by co-administration of the AHc-C antigen with MCP-3 or MDC/CCL22. This strategy elicited high levels of humoral immune responses and protection against BoNT/A. The enhanced potency was further boosted by co-administration of the AHc-C antigen with both MCP-3 and MDC/CCL22 in Balb/c mice, but not by co-administration of AHc-C antigen with the MCP-3-MDC/CCL22 fusion. Co-immunization with both the MCP-3 and MDC/CCL22 constructs induced the highest levels of humoral immunity and protective potency against BoNT/A. Our results indicated that MCP-3 and MDC/CCL22 are effective molecular adjuvants of the immune responses induced by the AHc-C-expressing DNA vaccine when delivered by co-administration of the individual chemokines, but not when delivered in the form of a chemokine/antigen fusion. Thus, we describe an alternative strategy to the design and optimization of DNA vaccine constructs based on co-administration of the antigen with the chemokine rather than in the form of a chemokine/antigen fusion. PMID:25952465

  3. Significantly enhanced bioavailability of niclosamide through submicron lipid emulsions with or without PEG-lipid: a comparative study.

    PubMed

    Zhang, Xingwang; Zhang, Yong; Zhang, Tianpeng; Zhang, Jianping; Wu, Baojian

    2015-01-01

    Niclosamide (NL) has demonstrated its great potential in fighting against leukaemia recently. However, either oral or systemic delivery of NL is challenged by its insoluble nature. Here, we developed two different NL-loaded submicron lipid emulsions (NL-SLEs) and compared their suitability in bioavailability enhancement. Conventional and PEGylated NL-SLEs (NL-CSLEs and NL-PSLEs) were prepared by melt dispersion/high pressure homogenisation technique. They were about 307.8 and 162.2 nm in particle size, respectively, and both of them possessed satisfactory stability and drug load (>9.0%). After oral administration, significantly enhanced bioavailability was achieved through NL-CSLEs and NL-PSLEs (441.11 and 463.55% relative to the reference). Apart from global size, NL-CSLEs and NL-PSLEs exhibited similar attributes in release, lipolysis, mucin binding, etc. Taken together, SLEs with or without PEG-lipid have shown to be promising for oral delivery of NL. PEG-lipid could significantly reduce the particle size of SLEs. But, macromolecular PEG-lipid was required to effectively stealth the lipid carriers. PMID:26079596

  4. Enhancement of adaptive immunity to Neisseria gonorrhoeae by local intravaginal administration of microencapsulated interleukin 12.

    PubMed

    Liu, Yingru; Egilmez, Nejat K; Russell, Michael W

    2013-12-01

    Gonorrhea remains one of the most frequent infectious diseases, and Neisseria gonorrhoeae is emerging as resistant to most available antibiotics, yet it does not induce a state of specific protective immunity against reinfection. Our recent studies have demonstrated that N. gonorrhoeae proactively suppresses host T-helper (Th) 1/Th2-mediated adaptive immune responses, which can be manipulated to generate protective immunity. Here we show that intravaginally administered interleukin 12 (IL-12) encapsulated in sustained-release polymer microspheres significantly enhanced both Th1 and humoral immune responses in a mouse model of genital gonococcal infection. Treatment of mice with IL-12 microspheres during gonococcal challenge led to faster clearance of infection and induced resistance to reinfection, with the generation of gonococcus-specific circulating immunoglobulin G and vaginal immunoglobulin A and G antibodies. These results suggest that local administration of microencapsulated IL-12 can serve as a novel therapeutic and prophylactic strategy against gonorrhea, with implications for the development of an effective vaccine. PMID:24048962

  5. Light-concentrating plasmonic Au superstructures with significantly visible-light-enhanced catalytic performance.

    PubMed

    Yang, Jinhu; Li, Ying; Zu, Lianhai; Tong, Lianming; Liu, Guanglei; Qin, Yao; Shi, Donglu

    2015-04-22

    Noble metals are well-known for their surface plasmon resonance effect that enables strong light absorption typically in the visible regions for gold and silver. However, unlike semiconductors, noble metals are commonly considered incapable of catalyzing reactions via photogenerated electron-hole pairs due to their continuous energy band structures. So far, photonically activated catalytic system based on pure noble metal nanostructures has seldom been reported. Here, we report the development of three different novel plasmonic Au superstructures comprised of Au nanoparticles, multiple-twinned nanoparticles and nanoworms assembling on the surfaces of SiO2 nanospheres respectively via a well-designed synthetic strategy. It is found that these novel Au superstructures show enhanced broadband visible-light absorption due to the plasmon resonance coupling within the superstructures, and thus can effectively focus the energy of photon fluxes to generate much more excited hot electrons and holes for promoting catalytic reactions. Accordingly, these Au superstructures exhibit significantly visible-light-enhanced catalytic efficiency (up to ∼264% enhancement) for the commercial reaction of p-nitrophenol reduction. PMID:25840556

  6. Enhancement of hepatocarcinogenesis by sequential administration of chemicals: summation versus promotion effects.

    PubMed

    Williams, G M; Katayama, S; Ohmori, T

    1981-01-01

    A comparative study was made of the sequential administration of the liver carcinogen, diethylnitrosamine (DEN), or the liver tumor promoter, phenobarbital, given after the liver carcinogen, N-2-fluorenylacetamide (FAA). The effects of the second carcinogen on preneoplastic cellular lesions induced by the first carcinogen were comparable to the effects of the promoter. In addition, both sequential exposures enhanced the ultimate carcinogenic effect, although the combination of FAA followed by DEN resulted in a greater number of malignant neoplasms. Thus, enhancement of carcinogenesis by a second chemical cannot be used by itself as evidence of a promoting action. Approaches to the more precise definition of promoters include exclusion of genotoxicity, identification of epigenetic mechanisms and lack of a summation effect with administration prior to genotoxic carcinogens. PMID:6119166

  7. The mother as hunter: significant reduction in foraging costs through enhancements of predation in maternal rats.

    PubMed

    Kinsley, Craig Howard; Blair, Jamie C; Karp, Natalie E; Hester, Naomi W; McNamara, Ilan M; Orthmeyer, Angela L; McSweeney, Molly C; Bardi, Massimo M; Karelina, Kate; Christon, Lillian M; Sirkin, Maxwell R; Victoria, Lindsay W; Skurka, Danielle J; Fyfe, Christian R; Hudepohl, Margaret B; Felicio, Luciano F; Franssen, R Adam; Meyer, Elizabeth E A; da Silva, Ilton S; Lambert, Kelly G

    2014-09-01

    In previous laboratory investigations, we have identified enhanced cognition and reduced stress in parous rats, which are likely adaptations in mothers needing to efficiently exploit resources to maintain, protect and provision their immature offspring. Here, in a series of seven behavioral tests on rats, we examined a natural interface between cognition and resource gathering: predation. Experiment 1 compared predatory behavior (toward crickets) in age-matched nulliparous mothers (NULLs) and postpartum lactating mothers (LACTs), revealing a highly significant enhancement of predation in LACT females (mean = -65s in LACTs, vs. -270s in NULLs). Experiment 2 examined the possibility that LACTs, given their increased metabolic rate, were hungrier, and thus more motivated to hunt; doubling the length of time of food deprivation in NULLs did not decrease their predatory latencies. Experiments 3-5, which examined sensory regulation of the effect, indicated that olfaction (anosmia), audition (blockade with white noise), and somatosensation (trimming the vibrissae) appear to play little role in the behavioral enhancement observed in the LACTs; Experiment 6 examined the possibility that visual augmentations may facilitate the improvements in predation; testing LACTs in a 0-lux environment eliminated the behavioral advantage (increasing their latencies from -65s to -212s), which suggests that temporary augmentation to the visual system may be important, and with hormone-neural alterations therein a likely candidate for further study. In contrast, testing NULLS in the 0-lux environment had the opposite effect, reducing their latency to catch the cricket (from -270s to -200s). Finally, Experiment 7 examined the development of predatory behavior in Early-pregnant (PREG), Mid-PREG, and Late-PREG females. Here, we observed a significant enhancement of predation in Mid-PREG and Late-PREG females--at a time when maternity-associated bodily changes would be expected to diminish

  8. Significant enhancement of negative secondary ion yields by cluster ion bombardment combined with cesium flooding.

    PubMed

    Philipp, Patrick; Angerer, Tina B; Sämfors, Sanna; Blenkinsopp, Paul; Fletcher, John S; Wirtz, Tom

    2015-10-01

    In secondary ion mass spectrometry (SIMS), the beneficial effect of cesium implantation or flooding on the enhancement of negative secondary ion yields has been investigated in detail for various semiconductor and metal samples. All results have been obtained for monatomic ion bombardment. Recent progress in SIMS is based to a large extent on the development and use of cluster primary ions. In this work we show that the enhancement of negative secondary ions induced by the combination of ion bombardment with simultaneous cesium flooding is valid not only for monatomic ion bombardment but also for cluster primary ions. Experiments carried out using C60+ and Ar4000+ bombardment on silicon show that yields of negative secondary silicon ions can be optimized in the same way as by Ga+ and Cs+ bombardment. Both for monatomic and cluster ion bombardment, the optimization does not depend on the primary ion species. Hence, it can be assumed that the silicon results are also valid for other cluster primary ions and that results obtained for monatomic ion bombardment on other semiconductor and metal samples are also valid for cluster ion bombardment. In SIMS, cluster primary ions are also largely used for the analysis of organic matter. For polycarbonate, our results show that Ar4000+ bombardment combined with cesium flooding enhances secondary ion signals by a factor of 6. This can be attributed to the removal of charging effects and/or reduced fragmentation, but no major influence on ionization processes can be observed. The use of cesium flooding for the imaging of cells was also investigated and a significant enhancement of secondary ion yields was observed. Hence, cesium flooding has also a vast potential for SIMS analyses with cluster ion bombardment. PMID:26378890

  9. Intranasal oxytocin administration is associated with enhanced endogenous pain inhibition and reduced negative mood states

    PubMed Central

    Goodin, Burel R.; Anderson, Austen J. B.; Freeman, Emily L.; Bulls, Hailey W.; Robbins, Meredith T.; Ness, Timothy J.

    2014-01-01

    Objectives This study examined whether the administration of intranasal oxytocin was associated with pain sensitivity, endogenous pain inhibitory capacity, and negative mood states. Methods A total of 30 pain-free, young adults each completed three laboratory sessions on consecutive days. The first session (baseline) assessed ischemic pain sensitivity, endogenous pain inhibition via conditioned pain modulation (CPM), and negative mood using the Profile of Mood States (POMS). CPM was tested on the dominant forearm and ipsilateral masseter muscle using algometry (test stimulus) and the cold pressor task (conditioning stimulus; non-dominant hand). For the second and third sessions, participants initially completed the State-Trait Anxiety Inventory (STAI) and then self-administered a single (40IU/1mL) dose of intranasal oxytocin or placebo in a randomized counter-balanced order. Thirty minutes post-administration, participants again completed the STAI and repeated assessments of ischemic pain sensitivity and CPM followed by the POMS. Results Findings demonstrated that ischemic pain sensitivity did not significantly differ across the three study sessions. CPM at the masseter, but not the forearm, was significantly greater following administration of oxytocin compared to placebo. Negative mood was also significantly lower following administration of oxytocin compared to placebo. Similarly, anxiety significantly decreased following administration of oxytocin but not placebo. Discussion This study incorporated a placebo-controlled, double-blind, within-subjects crossover design with randomized administration of intranasal oxytocin and placebo. The data suggest that the administration of intranasal oxytocin may augment endogenous pain inhibitory capacity and reduce negative mood states including anxiety. PMID:25370147

  10. Significant enhancement of magnetoresistance with the reduction of particle size in nanometer scale.

    PubMed

    Das, Kalipada; Dasgupta, P; Poddar, A; Das, I

    2016-01-01

    The Physics of materials with large magnetoresistance (MR), defined as the percentage change of electrical resistance with the application of external magnetic field, has been an active field of research for quite some times. In addition to the fundamental interest, large MR has widespread application that includes the field of magnetic field sensor technology. New materials with large MR is interesting. However it is more appealing to vast scientific community if a method describe to achieve many fold enhancement of MR of already known materials. Our study on several manganite samples [La(1-x)Ca(x)MnO3 (x = 0.52, 0.54, 0.55)] illustrates the method of significant enhancement of MR with the reduction of the particle size in nanometer scale. Our experimentally observed results are explained by considering model consisted of a charge ordered antiferromagnetic core and a shell having short range ferromagnetic correlation between the uncompensated surface spins in nanoscale regime. The ferromagnetic fractions obtained theoretically in the nanoparticles has been shown to be in the good agreement with the experimental results. The method of several orders of magnitude improvement of the magnetoresistive property will have enormous potential for magnetic field sensor technology. PMID:26837285

  11. Significant enhancement of magnetoresistance with the reduction of particle size in nanometer scale

    NASA Astrophysics Data System (ADS)

    Das, Kalipada; Dasgupta, P.; Poddar, A.; Das, I.

    2016-02-01

    The Physics of materials with large magnetoresistance (MR), defined as the percentage change of electrical resistance with the application of external magnetic field, has been an active field of research for quite some times. In addition to the fundamental interest, large MR has widespread application that includes the field of magnetic field sensor technology. New materials with large MR is interesting. However it is more appealing to vast scientific community if a method describe to achieve many fold enhancement of MR of already known materials. Our study on several manganite samples [La1-xCaxMnO3 (x = 0.52, 0.54, 0.55)] illustrates the method of significant enhancement of MR with the reduction of the particle size in nanometer scale. Our experimentally observed results are explained by considering model consisted of a charge ordered antiferromagnetic core and a shell having short range ferromagnetic correlation between the uncompensated surface spins in nanoscale regime. The ferromagnetic fractions obtained theoretically in the nanoparticles has been shown to be in the good agreement with the experimental results. The method of several orders of magnitude improvement of the magnetoresistive property will have enormous potential for magnetic field sensor technology.

  12. Significant enhancement of magnetoresistance with the reduction of particle size in nanometer scale

    PubMed Central

    Das, Kalipada; Dasgupta, P.; Poddar, A.; Das, I.

    2016-01-01

    The Physics of materials with large magnetoresistance (MR), defined as the percentage change of electrical resistance with the application of external magnetic field, has been an active field of research for quite some times. In addition to the fundamental interest, large MR has widespread application that includes the field of magnetic field sensor technology. New materials with large MR is interesting. However it is more appealing to vast scientific community if a method describe to achieve many fold enhancement of MR of already known materials. Our study on several manganite samples [La1−xCaxMnO3 (x = 0.52, 0.54, 0.55)] illustrates the method of significant enhancement of MR with the reduction of the particle size in nanometer scale. Our experimentally observed results are explained by considering model consisted of a charge ordered antiferromagnetic core and a shell having short range ferromagnetic correlation between the uncompensated surface spins in nanoscale regime. The ferromagnetic fractions obtained theoretically in the nanoparticles has been shown to be in the good agreement with the experimental results. The method of several orders of magnitude improvement of the magnetoresistive property will have enormous potential for magnetic field sensor technology. PMID:26837285

  13. OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer

    PubMed Central

    Weixler, Benjamin; Cremonesi, Eleonora; Sorge, Roberto; Muraro, Manuele Giuseppe; Delko, Tarik; Nebiker, Christian A.; Däster, Silvio; Governa, Valeria; Amicarella, Francesca; Soysal, Savas D.; Kettelhack, Christoph; von Holzen, Urs W.; Eppenberger-Castori, Serenella; Spagnoli, Giulio C.; Oertli, Daniel; Iezzi, Giandomenica; Terracciano, Luigi; Tornillo, Luigi

    2015-01-01

    Background OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective. Methods OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated. Results OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40high/CD8high infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40low/CD8high, OX40high/CD8low or OX40low/CD8low infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40high/CD8high density infiltrates showed an overall survival similar to that of all stage I CRC included in the study. Conclusions OX40high/CD8high density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers. PMID:26439988

  14. Does Enhanced External Counterpulsation (EECP) Significantly Affect Myocardial Perfusion?: A Systematic Review & Meta-Analysis

    PubMed Central

    Qin, Xiaoxia; Deng, Yanye; Wu, Dandong; Yu, Lehua; Huang, Rongzhong

    2016-01-01

    Background Enhanced external counterpulsation (EECP) is currently applied for treating coronary artery disease (CAD) patients. However, the mechanism(s) by which EECP ameliorates angina pectoris and long-term left ventricular function remain largely unknown. The aim of this study will be to assess whether EECP significantly affects myocardial perfusion in CAD patients through a systematic review and meta-analysis of the available literature. Methods MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched for prospective studies on CAD patients that underwent EECP and reported myocardial perfusion data pre- and post-EECP. The impact of EECP was assessed based on the weighted mean difference (WMD) in myocardial perfusion from pre-EECP to post-EECP. Statistical heterogeneity was assessed by the I2 index. Publication bias was assessed through visual inspection of the funnel plot as well as Begg’s and Egger’s testing. Results Standard EECP therapy (i.e., 35–36 one-hour sessions within a seven-week period) significantly increased myocardial perfusion in CAD patients (pooled WMD: -0.19, 95% CI: -0.38 to 0.00, p = 0.049). A random effects analysis was applied on account of significant heterogeneity (I2 = 89.1%, p = 0.000). There was no evidence of significant publication bias (Begg’s p = 0.091; Egger’s p = 0.282). Conclusions Standard EECP therapy significantly increases myocardial perfusion in CAD patients. This study’s findings support the continued use of standard EECP therapy in CAD patients and provides one putative physiological mechanism to help explain the improvements in angina pectoris and long-term left ventricular function observed in CAD patients after EECP therapy. PMID:27045935

  15. Prognostic and Clinicopathological Significance of Transducer-Like Enhancer of Split 1 Expression in Gastric Cancer

    PubMed Central

    Lee, Ji-Hye; Son, Myoung-Won; Kim, Kyung-Ju; Oh, Mee-Hye; Cho, Hyundeuk; Lee, Hyun Ju; Jang, Si-Hyong

    2016-01-01

    Purpose Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. Materials and Methods Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. Results In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. Conclusions We suggested that TLE1 expression is a good prognostic indicator in GCs. PMID:27104023

  16. Significantly enhanced robustness and electrochemical performance of flexible carbon nanotube-based supercapacitors by electrodepositing polypyrrole

    NASA Astrophysics Data System (ADS)

    Chen, Yanli; Du, Lianhuan; Yang, Peihua; Sun, Peng; Yu, Xiang; Mai, Wenjie

    2015-08-01

    Here, we report robust, flexible CNT-based supercapacitor (SC) electrodes fabricated by electrodepositing polypyrrole (PPy) on freestanding vacuum-filtered CNT film. These electrodes demonstrate significantly improved mechanical properties (with the ultimate tensile strength of 16 MPa), and greatly enhanced electrochemical performance (5.6 times larger areal capacitance). The major drawback of conductive polymer electrodes is the fast capacitance decay caused by structural breakdown, which decreases cycling stability but this is not observed in our case. All-solid-state SCs assembled with the robust CNT/PPy electrodes exhibit excellent flexibility, long lifetime (95% capacitance retention after 10,000 cycles) and high electrochemical performance (a total device volumetric capacitance of 4.9 F/cm3). Moreover, a flexible SC pack is demonstrated to light up 53 LEDs or drive a digital watch, indicating the broad potential application of our SCs for portable/wearable electronics.

  17. Significant Broadband Photocurrent Enhancement by Au-CZTS Core-Shell Nanostructured Photocathodes

    NASA Astrophysics Data System (ADS)

    Zhang, Xuemei; Wu, Xu; Centeno, Anthony; Ryan, Mary P.; Alford, Neil M.; Riley, D. Jason; Xie, Fang

    2016-03-01

    Copper zinc tin sulfide (CZTS) is a promising material for harvesting solar energy due to its abundance and non-toxicity. However, its poor performance hinders their wide application. In this paper gold (Au) nanoparticles are successfully incorporated into CZTS to form Au@CZTS core-shell nanostructures. The photocathode of Au@CZTS nanostructures exhibits enhanced optical absorption characteristics and improved incident photon-to-current efficiency (IPCE) performance. It is demonstrated that using this photocathode there is a significant increase of the power conversion efficiency (PCE) of a photoelectrochemical solar cell of 100% compared to using a CZTS without Au core. More importantly, the PCE of Au@CZTS photocathode improved by 15.8% compared to standard platinum (Pt) counter electrode. The increased efficiency is attributed to plasmon resonance energy transfer (PRET) between the Au nanoparticle core and the CZTS shell at wavelengths shorter than the localized surface plasmon resonance (LSPR) peak of the Au and the semiconductor bandgap.

  18. Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

    ERIC Educational Resources Information Center

    Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

    2011-01-01

    Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

  19. Protect and enhance: Lowi's juridical democracy and the prevention of significant deterioration of air quality

    SciTech Connect

    Meiburg, A.S.

    1986-01-01

    The capture of Federal regulatory agencies by the groups they were supposed to be regulating has been a topic of concern in the traditional literature of public administration. In his influential book The End of Liberalism, Professor Theordore Lowi suggested that capture resulted in part from vauge delegations of authority of Congress to regulatory agencies. Lowi argued that democracy would be better served if Congress were more specific in drafting laws, if agencies made greater use of formal rulemaking in implementing them, and if the courts rejected statutes which contained excessively vague delegations of authority - a remedy which he labeled juridicial democracy. This dissertation examines Lowi's theory in light of the experience of Congress and the Environmental Protection Agency (EPA) with the requirements of the Clean Air Act to prevent the significant deterioration of air quality in areas where air was already relatively clean. The history of the program to develop and carry out these requirements, known as PSD, is described in detail from its inception in the late 1960's through EPA's final regulations in 1980. Special attention is given to the actions taken by EPA after environmental groups successfully used the courts to force EPA to develop a PSD program in 1974, how Congress responded by amending the Clean Air Act in 1977, and the difficulties these amendments and subsequent additional court reviews caused for EPA.

  20. Graphene Oxide Quantum Dots Covalently Functionalized PVDF Membrane with Significantly-Enhanced Bactericidal and Antibiofouling Performances.

    PubMed

    Zeng, Zhiping; Yu, Dingshan; He, Ziming; Liu, Jing; Xiao, Fang-Xing; Zhang, Yan; Wang, Rong; Bhattacharyya, Dibakar; Tan, Timothy Thatt Yang

    2016-01-01

    Covalent bonding of graphene oxide quantum dots (GOQDs) onto amino modified polyvinylidene fluoride (PVDF) membrane has generated a new type of nano-carbon functionalized membrane with significantly enhanced antibacterial and antibiofouling properties. A continuous filtration test using E. coli containing feedwater shows that the relative flux drop over GOQDs modified PVDF is 23%, which is significantly lower than those over pristine PVDF (86%) and GO-sheet modified PVDF (62%) after 10 h of filtration. The presence of GOQD coating layer effectively inactivates E. coli and S. aureus cells, and prevents the biofilm formation on the membrane surface, producing excellent antimicrobial activity and potentially antibiofouling capability, more superior than those of previously reported two-dimensional GO sheets and one-dimensional CNTs modified membranes. The distinctive antimicrobial and antibiofouling performances could be attributed to the unique structure and uniform dispersion of GOQDs, enabling the exposure of a larger fraction of active edges and facilitating the formation of oxidation stress. Furthermore, GOQDs modified membrane possesses satisfying long-term stability and durability due to the strong covalent interaction between PVDF and GOQDs. This study opens up a new synthetic avenue in the fabrication of efficient surface-functionalized polymer membranes for potential waste water treatment and biomolecules separation. PMID:26832603

  1. Graphene Oxide Quantum Dots Covalently Functionalized PVDF Membrane with Significantly-Enhanced Bactericidal and Antibiofouling Performances

    NASA Astrophysics Data System (ADS)

    Zeng, Zhiping; Yu, Dingshan; He, Ziming; Liu, Jing; Xiao, Fang-Xing; Zhang, Yan; Wang, Rong; Bhattacharyya, Dibakar; Tan, Timothy Thatt Yang

    2016-02-01

    Covalent bonding of graphene oxide quantum dots (GOQDs) onto amino modified polyvinylidene fluoride (PVDF) membrane has generated a new type of nano-carbon functionalized membrane with significantly enhanced antibacterial and antibiofouling properties. A continuous filtration test using E. coli containing feedwater shows that the relative flux drop over GOQDs modified PVDF is 23%, which is significantly lower than those over pristine PVDF (86%) and GO-sheet modified PVDF (62%) after 10 h of filtration. The presence of GOQD coating layer effectively inactivates E. coli and S. aureus cells, and prevents the biofilm formation on the membrane surface, producing excellent antimicrobial activity and potentially antibiofouling capability, more superior than those of previously reported two-dimensional GO sheets and one-dimensional CNTs modified membranes. The distinctive antimicrobial and antibiofouling performances could be attributed to the unique structure and uniform dispersion of GOQDs, enabling the exposure of a larger fraction of active edges and facilitating the formation of oxidation stress. Furthermore, GOQDs modified membrane possesses satisfying long-term stability and durability due to the strong covalent interaction between PVDF and GOQDs. This study opens up a new synthetic avenue in the fabrication of efficient surface-functionalized polymer membranes for potential waste water treatment and biomolecules separation.

  2. Graphene Oxide Quantum Dots Covalently Functionalized PVDF Membrane with Significantly-Enhanced Bactericidal and Antibiofouling Performances

    PubMed Central

    Zeng, Zhiping; Yu, Dingshan; He, Ziming; Liu, Jing; Xiao, Fang-Xing; Zhang, Yan; Wang, Rong; Bhattacharyya, Dibakar; Tan, Timothy Thatt Yang

    2016-01-01

    Covalent bonding of graphene oxide quantum dots (GOQDs) onto amino modified polyvinylidene fluoride (PVDF) membrane has generated a new type of nano-carbon functionalized membrane with significantly enhanced antibacterial and antibiofouling properties. A continuous filtration test using E. coli containing feedwater shows that the relative flux drop over GOQDs modified PVDF is 23%, which is significantly lower than those over pristine PVDF (86%) and GO-sheet modified PVDF (62%) after 10 h of filtration. The presence of GOQD coating layer effectively inactivates E. coli and S. aureus cells, and prevents the biofilm formation on the membrane surface, producing excellent antimicrobial activity and potentially antibiofouling capability, more superior than those of previously reported two-dimensional GO sheets and one-dimensional CNTs modified membranes. The distinctive antimicrobial and antibiofouling performances could be attributed to the unique structure and uniform dispersion of GOQDs, enabling the exposure of a larger fraction of active edges and facilitating the formation of oxidation stress. Furthermore, GOQDs modified membrane possesses satisfying long-term stability and durability due to the strong covalent interaction between PVDF and GOQDs. This study opens up a new synthetic avenue in the fabrication of efficient surface-functionalized polymer membranes for potential waste water treatment and biomolecules separation. PMID:26832603

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

    PubMed

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

    2016-04-20

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

  4. Combined administration of (L)-cystine and (L)-theanine enhances immune functions and protects against influenza virus infection in aged mice.

    PubMed

    Takagi, Yasuhiro; Kurihara, Shigekazu; Higashi, Natsumi; Morikawa, Saeko; Kase, Tetsuo; Maeda, Akiko; Arisaka, Harumi; Shibahara, Susumu; Akiyama, Yukio

    2010-02-01

    Cell-mediated and humoral immune responses are attenuated with aging. Intracellular glutathione (GSH) levels also decrease with aging. Previously, we have reported that combined administration of (L)-cystine and (L)-theanine enhances antigen-specific IgG production, partly through augmentation of GSH levels and T helper 2-mediated responses in 12-week-old mice. These findings suggest that combined administration of (L)-cystine and (L)-theanine to aged mice improves immune responses via increase of GSH synthesis. Here, we examined the effects of combined administration of (L)-cystine and (L)-theanine on antigen-specific antibody production and influenza virus infection in aged mice. Combined administration of these amino acids for 14 days before primary immunization significantly enhanced the serum antigen-specific IgM and IgG levels in 24-month-old mice. Furthermore, 13-month-old mice co-treated with these amino acids orally for 10 days had significantly lower lung viral titers than controls at 6 days after influenza virus infection. In addition, this co-treatment also significantly prevented the weight loss associated with infection. Enhancement of anti-influenza-virus IgG antibodies by combined administration of (L)-cystine and (L)-theanine was seen 10 days after infection. The significantly elevated serum interleukin-10/interferon-gamma ratio and gamma-glutamylcysteine synthetase mRNA expression, which is the rate-limiting enzyme of GSH synthesis, in the spleen 3 days after infection may have contributed to the observed beneficial effects. These results suggest that combined administration of (L)-cystine and (L)-theanine enhances immune function and GSH synthesis which are compromised with advanced age, and may become a useful strategy in healthy aging. PMID:19940390

  5. In-situ administration of dendritic cells following argon-helium cryosurgery enhances specific antiglioma immunity in mice.

    PubMed

    Lin, Chunnan; Wang, Qifu; Lu, Guohui; Yin, Zhilin; He, Xiaozheng; Xu, Hongchao; Pan, Jun; Zhang, Shizhong

    2014-08-20

    Dendritic cells (DCs) are highly specialized antigen-presenting cells that play a key role in the activation of naive T cells. With an aim to explore whether in-situ administration of DCs following argon-helium cryosurgery could enhance specific antiglioma immunity in mice, we evaluated the validity of this approach in a murine subcutaneous GL261 glioma model. C57BL/6 mice models bearing subcutaneous GL261 glioma were established and then divided into four groups, namely, no-treatment group (n=14), DC group (n=14), cryosurgery group (n=15), and cryosurgery+DC group (n=15). Compared with the other groups, cryosurgery combined with DCs injection reduced tumor sizes and significantly prolonged survival. In addition, the combined treatment resulted in significantly increasing percentages of CD3, CD3CD4 cells, the ratio of CD3CD4/CD3CD8, and the level of serum interleukin-12 10 days after treatments. Furthermore, in the combined treatment group, Th1 cells were significantly higher than those in the other groups, and the splenic cytotoxic T lymphocyte of mice showed significantly increasing specific cytotoxicity against GL261 cells. These results indicated that in addition to the destruction of tumor, cryosurgery combined with DCs injection enhanced systemic antitumor immunity, suggesting the potential usefulness of the combined treatment in the clinical management of gliomas. PMID:24942351

  6. Individual versus Significant Other-Enhanced Brief Motivational Intervention for Alcohol in Emergency Care

    PubMed Central

    Monti, Peter M.; Colby, Suzanne M.; Mastroleo, Nadine R.; Barnett, Nancy P.; Gwaltney, Chad J.; Apodaca, Timothy R.; Rohsenow, Damaris J.; Magill, Molly; Gogineni, Aruna; Mello, Michael J.; Biffl, Walter L.; Cioffi, William G.

    2014-01-01

    Objective Effects of brief motivational interventions (BMIs) for heavy drinkers identified by alcohol-related emergency department (ED) visits are mixed. The successes of including significant others (SOs) in behavioral treatment suggest that involving SOs in ED-delivered BMI might prove beneficial. This study investigated the relative efficacy of an SO-enhanced Motivational Intervention (SOMI) compared to an Individual Motivational Intervention (IMI) to address heavy drinking in emergency care settings. Method ED (n = 317) or trauma unit (n = 89) patients were randomly assigned to receive either an IMI or an SOMI and were re-assessed at 6 and 12 months for alcohol consumption, alcohol-related consequences, and perceived alcohol-specific SO support. Results GEE analyses showed consistent reductions over time for both alcohol consumption and consequences. At one-year follow up, the average reduction in total drinks consumed per week was greater for patients in the SOMI condition than the IMI condition. In SOMI, 9.4% more patients moved to within the national guidelines for weekly drinking than did IMI patients. Frequency of heavy drinking and negative alcohol consequences showed no differential effects of intervention. Conclusions Emergence of a modest treatment effect at 12 months suggests that SO involvement in the SOMI condition may have led to more sustained positive influence on patient drinking than in the IMI condition. Implications and limitations regarding SO involvement in brief treatment are discussed. PMID:25111430

  7. Significant Enhancement of Water Splitting Activity of N-Carbon Electrocatalyst by Trace Level Co Doping.

    PubMed

    Bayatsarmadi, Bita; Zheng, Yao; Tang, Youhong; Jaroniec, Mietek; Qiao, Shi-Zhang

    2016-07-01

    Replacement of precious metal electrocatalysts with highly active and cost efficient alternatives for complete water splitting at low voltage has attracted a growing attention in recent years. Here, this study reports a carbon-based composite co-doped with nitrogen and trace amount of metallic cobalt (1 at%) as a bifunctional electrocatalyst for water splitting at low overpotential and high current density. An excellent electrochemical activity of the newly developed electrocatalyst originates from its graphitic nanostructure and highly active Co-Nx sites. In the case of carefully optimized sample of this electrocatalyst, 10 mA cm(-2) current density can be achieved for two half reactions in alkaline solutions-hydrogen evolution reaction and oxygen evolution reaction-at low overpotentials of 220 and 350 mV, respectively, which are smaller than those previously reported for nonprecious metal and metal-free counterparts. Based on the spectroscopic and electrochemical investigations, the newly identified Co-Nx sites in the carbon framework are responsible for high electrocatalytic activity of the Co,N-doped carbon. This study indicates that a trace level of the introduced Co into N-doped carbon can significantly enhance its electrocatalytic activity toward water splitting. PMID:27246288

  8. Nanoporosity Significantly Enhances the Biological Performance of Engineered Glass Tissue Scaffolds

    PubMed Central

    Wang, Shaojie; Kowal, Tia J.; Marei, Mona K.

    2013-01-01

    Nanoporosity is known to impact the performance of implants and scaffolds such as bioactive glass (BG) scaffolds, either by providing a higher concentration of bioactive chemical species from enhanced surface area, or due to inherent nanoscale topology, or both. To delineate the role of these two characteristics, BG scaffolds have been fabricated with nearly identical surface area (81 and 83±2 m2/g) but significantly different pore size (av. 3.7 and 17.7 nm) by varying both the sintering temperature and the ammonia concentration during the solvent exchange phase of the sol-gel fabrication process. In vitro tests performed with MC3T3-E1 preosteoblast cells on such scaffolds show that initial cell attachment is increased on samples with the smaller nanopore size, providing the first direct evidence of the influence of nanopore topography on cell response to a bioactive structure. Furthermore, in vivo animal tests in New Zealand rabbits (subcutaneous implantation) indicate that nanopores promote colonization and cell penetration into these scaffolds, further demonstrating the favorable effects of nanopores in tissue-engineering-relevant BG scaffolds. PMID:23427819

  9. Significant Broadband Photocurrent Enhancement by Au-CZTS Core-Shell Nanostructured Photocathodes

    PubMed Central

    Zhang, Xuemei; Wu, Xu; Centeno, Anthony; Ryan, Mary P.; Alford, Neil M.; Riley, D. Jason; Xie, Fang

    2016-01-01

    Copper zinc tin sulfide (CZTS) is a promising material for harvesting solar energy due to its abundance and non-toxicity. However, its poor performance hinders their wide application. In this paper gold (Au) nanoparticles are successfully incorporated into CZTS to form Au@CZTS core-shell nanostructures. The photocathode of Au@CZTS nanostructures exhibits enhanced optical absorption characteristics and improved incident photon-to-current efficiency (IPCE) performance. It is demonstrated that using this photocathode there is a significant increase of the power conversion efficiency (PCE) of a photoelectrochemical solar cell of 100% compared to using a CZTS without Au core. More importantly, the PCE of Au@CZTS photocathode improved by 15.8% compared to standard platinum (Pt) counter electrode. The increased efficiency is attributed to plasmon resonance energy transfer (PRET) between the Au nanoparticle core and the CZTS shell at wavelengths shorter than the localized surface plasmon resonance (LSPR) peak of the Au and the semiconductor bandgap. PMID:26997140

  10. Significant Broadband Photocurrent Enhancement by Au-CZTS Core-Shell Nanostructured Photocathodes.

    PubMed

    Zhang, Xuemei; Wu, Xu; Centeno, Anthony; Ryan, Mary P; Alford, Neil M; Riley, D Jason; Xie, Fang

    2016-01-01

    Copper zinc tin sulfide (CZTS) is a promising material for harvesting solar energy due to its abundance and non-toxicity. However, its poor performance hinders their wide application. In this paper gold (Au) nanoparticles are successfully incorporated into CZTS to form Au@CZTS core-shell nanostructures. The photocathode of Au@CZTS nanostructures exhibits enhanced optical absorption characteristics and improved incident photon-to-current efficiency (IPCE) performance. It is demonstrated that using this photocathode there is a significant increase of the power conversion efficiency (PCE) of a photoelectrochemical solar cell of 100% compared to using a CZTS without Au core. More importantly, the PCE of Au@CZTS photocathode improved by 15.8% compared to standard platinum (Pt) counter electrode. The increased efficiency is attributed to plasmon resonance energy transfer (PRET) between the Au nanoparticle core and the CZTS shell at wavelengths shorter than the localized surface plasmon resonance (LSPR) peak of the Au and the semiconductor bandgap. PMID:26997140

  11. Significantly enhanced production of recombinant nitrilase by optimization of culture conditions and glycerol feeding.

    PubMed

    Liu, Jun-Feng; Zhang, Zhi-Jun; Li, Ai-Tao; Pan, Jiang; Xu, Jian-He

    2011-02-01

    The production of a recombinant nitrilase expressed in Escherichia coli JM109/pNLE was optimized in the present work. Various culture conditions and process parameters, including medium composition, inducer, induction condition, pH and temperature, were systematically examined. The results showed that nitrilase production in E. coli JM109/pNLE was greatly affected by the pH condition and the temperature in batch culture, and the highest nitrilase production was obtained when the fermentation was carried out at 37°C, initial pH 7.0 without control and E. coli was induced with 0.2 mM isopropyl-β-D-thiogalactoside at 4.0 h. Furthermore, enzyme production could be significantly enhanced by adopting the glycerol feeding strategy with lower flow rate. The enzyme expression was also authenticated by sodium dodecyl phosphate polyacrylamide gel electrophoresis analysis. Finally, under the optimized conditions for fed-batch culture, cell growth, specific activity and nitrilase production of the recombinant E. coli were increased by 9.0-, 5.5-, and 50-fold, respectively. PMID:20862583

  12. Affective significance enhances covert attention: roles of anxiety and word familiarity.

    PubMed

    Calvo, Manuel G; Eysenck, Michael W

    2008-11-01

    To investigate the processing of emotional words by covert attention, threat-related, positive, and neutral word primes were presented parafoveally (2.2 degrees away from fixation) for 150 ms, under gaze-contingent foveal masking, to prevent eye fixations. The primes were followed by a probe word in a lexical-decision task. In Experiment 1, results showed a parafoveal threat-anxiety superiority: Parafoveal prime threat words facilitated responses to probe threat words for high-anxiety individuals, in comparison with neutral and positive words, and relative to low-anxiety individuals. This reveals an advantage in threat processing by covert attention, without differences in overt attention. However, anxiety was also associated with greater familiarity with threat words, and the parafoveal priming effects were significantly reduced when familiarity was covaried out. To further examine the role of word knowledge, in Experiment 2, vocabulary and word familiarity were equated for low- and high-anxiety groups. In these conditions, the parafoveal threat-anxiety advantage disappeared. This suggests that the enhanced covert-attention effect depends on familiarity with words. PMID:18942034

  13. A Novel Peptide from Soybean Protein Isolate Significantly Enhances Resistance of the Organism under Oxidative Stress.

    PubMed

    Ma, Heran; Liu, Rui; Zhao, Ziyuan; Zhang, Zhixian; Cao, Yue; Ma, Yudan; Guo, Yi; Xu, Li

    2016-01-01

    Recent studies have indicated that protein hydrolysates have broad biological effects. In the current study we describe a novel antioxidative peptide, FDPAL, from soybean protein isolate (SPI). The aim of this study was to purify and characterize an antioxidative peptide from SPI and determine its antioxidative mechanism. LC-MS/MS was used to isolate and identify the peptide from SPI. The sequence of the peptide was determined to be Phe-Asp-Pro-Ala-Leu (FDPAL, 561 Da). FDPAL can cause significant enhancement of resistance to oxidative stress both in cells as well as simple organisms. In Caenorhabditis elegans (C. elegans), FDPAL can up-regulate the expression of certain genes associated with resistance. The antioxidant activity of this peptide can be attributed to the presence of a specific amino acid sequence. Results from our work suggest that FDPAL can facilitate potential applications of proteins carrying this sequence in the nutraceutical, bioactive material and clinical medicine areas, as well as in cosmetics and health care products. PMID:27455060

  14. A Novel Peptide from Soybean Protein Isolate Significantly Enhances Resistance of the Organism under Oxidative Stress

    PubMed Central

    Ma, Heran; Liu, Rui; Zhao, Ziyuan; Zhang, Zhixian; Cao, Yue; Ma, Yudan; Guo, Yi; Xu, Li

    2016-01-01

    Recent studies have indicated that protein hydrolysates have broad biological effects. In the current study we describe a novel antioxidative peptide, FDPAL, from soybean protein isolate (SPI). The aim of this study was to purify and characterize an antioxidative peptide from SPI and determine its antioxidative mechanism. LC–MS/MS was used to isolate and identify the peptide from SPI. The sequence of the peptide was determined to be Phe-Asp-Pro-Ala-Leu (FDPAL, 561 Da). FDPAL can cause significant enhancement of resistance to oxidative stress both in cells as well as simple organisms. In Caenorhabditis elegans (C. elegans), FDPAL can up-regulate the expression of certain genes associated with resistance. The antioxidant activity of this peptide can be attributed to the presence of a specific amino acid sequence. Results from our work suggest that FDPAL can facilitate potential applications of proteins carrying this sequence in the nutraceutical, bioactive material and clinical medicine areas, as well as in cosmetics and health care products. PMID:27455060

  15. Nanoparticle-enhanced electrical impedance detection and its potential significance in image tomography

    PubMed Central

    Liu, Ran; Jin, Cuiyun; Song, Fengjuan; Liu, Jing

    2013-01-01

    The conductivity and permittivity of tumors are known to differ significantly from those of normal tissues. Electrical impedance tomography (EIT) is a relatively new imaging method for exploiting these differences. However, the accuracy of data capture is one of the difficult problems urgently to be solved in the clinical application of EIT technology. A new concept of EIT sensitizers is put forward in this paper with the goal of expanding the contrast ratio of tumor and healthy tissue to enhance EIT imaging quality. The use of nanoparticles for changing tumor characteristics and determining the infiltration vector for easier detection has been widely accepted in the biomedical field. Ultra-pure water, normal saline, and gold nanoparticles, three kinds of material with large differences in electrical characteristics, are considered as sensitizers and undergo mathematical model analysis and animal experimentation. Our preliminary results suggest that nanoparticles are promising for sensitization work. Furthermore, in experimental and simulation results, we found that we should select different sensitizers for the detection of different types and stages of tumor. PMID:23319858

  16. Amorphous Semiconductor Nanowires Created by Site-Specific Heteroatom Substitution with Significantly Enhanced Photoelectrochemical Performance.

    PubMed

    He, Ting; Zu, Lianhai; Zhang, Yan; Mao, Chengliang; Xu, Xiaoxiang; Yang, Jinhu; Yang, Shihe

    2016-08-23

    Semiconductor nanowires that have been extensively studied are typically in a crystalline phase. Much less studied are amorphous semiconductor nanowires due to the difficulty for their synthesis, despite a set of characteristics desirable for photoelectric devices, such as higher surface area, higher surface activity, and higher light harvesting. In this work of combined experiment and computation, taking Zn2GeO4 (ZGO) as an example, we propose a site-specific heteroatom substitution strategy through a solution-phase ions-alternative-deposition route to prepare amorphous/crystalline Si-incorporated ZGO nanowires with tunable band structures. The substitution of Si atoms for the Zn or Ge atoms distorts the bonding network to a different extent, leading to the formation of amorphous Zn1.7Si0.3GeO4 (ZSGO) or crystalline Zn2(GeO4)0.88(SiO4)0.12 (ZGSO) nanowires, respectively, with different bandgaps. The amorphous ZSGO nanowire arrays exhibit significantly enhanced performance in photoelectrochemical water splitting, such as higher and more stable photocurrent, and faster photoresponse and recovery, relative to crystalline ZGSO and ZGO nanowires in this work, as well as ZGO photocatalysts reported previously. The remarkable performance highlights the advantages of the ZSGO amorphous nanowires for photoelectric devices, such as higher light harvesting capability, faster charge separation, lower charge recombination, and higher surface catalytic activity. PMID:27494205

  17. Enhanced immune response to foot-and-mouth disease vaccine by oral administration of ginseng stem-leaf saponins.

    PubMed

    Li, Renjun; Ma, Yanfen; Zhai, Lijuan; Lu, Yisong; Chi, Xiaoqing; Wu, Jiusheng; Hu, Songhua

    2016-08-01

    Vaccination is an important approach to the control of foot-and-mouth disease (FMD). This study evaluated the effect of oral administration of ginseng stem-leaf saponins (GSLS) on the immune response to FMD vaccine and the gut mucosal immunity in mice. In experiment 1, mice were orally administered GSLS or not treated as a control. The animals were then immunized twice with FMD vaccine. Blood was sampled weekly within five weeks after the boost immunization for measurement of serum IgG and the isotypes. In experiment 2, mice were orally administrated GSLS or not treated as a control. After that, splenocytes were prepared from sacrificed mice for lymphocyte proliferation assay and intestinal tissues were sampled for immunohistochemistry and histological examination. The results showed that oral administration of GSLS significantly enhanced serum IgG and the isotype responses to FMD vaccine as well as the number of intestinal intraepithelial lymphocytes (IELs) and immunoglobulin A (IgA)+ cells. Therefore, GSLS may be a potent oral adjuvant and deserve further study to improve vaccination in susceptible animals. PMID:27216768

  18. Enhanced nicotine self-administration and suppressed dopaminergic systems in a rat model of diabetes

    PubMed Central

    O'Dell, Laura E.; Natividad, Luis A.; Pipkin, Joseph A.; Roman, Francisco; Torres, Ivan; Jurado, Jesus; Torres, Oscar V.; Friedman, Theodore C.; Tenayuca, John M.; Nazarian, Arbi

    2013-01-01

    Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared in the nucleus accumbens (NAc) following 10 days of nicotine or saline IVSA. Dopamine levels in the NAc were also compared following nicotine administration. Lastly, nicotine metabolism and dose-dependent effects of nicotine IVSA were assessed. The results revealed that STZ-treated rats displayed enhanced nicotine intake and a robust increase in food and water intake relative to controls. Protein analysis revealed an increase in DAT and a decrease in D1 receptor levels in the NAc of STZ- versus vehicle-treated rats regardless of IVSA condition. STZ-treated rats also displayed suppressed NAc dopamine levels during baseline and in response to nicotine. STZ treatment did not alter our assessment of nicotine metabolism. Furthermore, STZ treatment increased nicotine IVSA in a dose-dependent manner. Our findings suggest that STZ-treatment increased the rewarding effects of nicotine. This suggests that strong reinforcing effects of nicotine may contribute to greater tobacco use in patients with diabetes. PMID:23834715

  19. Significant metal enhanced fluorescence of Ag2S quantum dots in the second near-infrared window

    NASA Astrophysics Data System (ADS)

    Theodorou, I. G.; Jawad, Z. A. R.; Qin, H.; Aboagye, E. O.; Porter, A. E.; Ryan, M. P.; Xie, F.

    2016-06-01

    The amplification of light in NIR-II from Ag2S QDs via metal enhanced fluorescence (MEF) is reported for the first time. Significant fluorescence enhancement of over 100 times for Ag2S QDs deposited on Au-nanostructured arrays, paves the way for novel sensing and imaging applications based on Ag2S QDs, with improved detection sensitivity and contrast enhancement.The amplification of light in NIR-II from Ag2S QDs via metal enhanced fluorescence (MEF) is reported for the first time. Significant fluorescence enhancement of over 100 times for Ag2S QDs deposited on Au-nanostructured arrays, paves the way for novel sensing and imaging applications based on Ag2S QDs, with improved detection sensitivity and contrast enhancement. Electronic supplementary information (ESI) available: Detailed description of experimental methods. See DOI: 10.1039/c6nr03220f

  20. Significant metal enhanced fluorescence of Ag2S quantum dots in the second near-infrared window.

    PubMed

    Theodorou, I G; Jawad, Z A R; Qin, H; Aboagye, E O; Porter, A E; Ryan, M P; Xie, F

    2016-07-14

    The amplification of light in NIR-II from Ag2S QDs via metal enhanced fluorescence (MEF) is reported for the first time. Significant fluorescence enhancement of over 100 times for Ag2S QDs deposited on Au-nanostructured arrays, paves the way for novel sensing and imaging applications based on Ag2S QDs, with improved detection sensitivity and contrast enhancement. PMID:27314986

  1. American ginseng significantly reduced the progression of high-fat-diet-enhanced colon carcinogenesis in ApcMin/+mice

    PubMed Central

    Yu, Chunhao; Wen, Xiao-Dong; Zhang, Zhiyu; Zhang, Chun-Feng; Wu, Xiaohui; He, Xin; Liao, Yang; Wu, Ningning; Wang, Chong-Zhi; Du, Wei; He, Tong-Chuan; Yuan, Chun-Su

    2015-01-01

    Background Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods A genetically engineered ApcMin/+ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results After oral ginseng administration (10–20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-1α (IL-1α), IL-1β, IL-6, tumor necrosis factor-α, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention. PMID:26199554

  2. Focused R&D For Electrochromic Smart Windowsa: Significant Performance and Yield Enhancements

    SciTech Connect

    Mark Burdis; Neil Sbar

    2003-01-31

    There is a need to improve the energy efficiency of building envelopes as they are the primary factor governing the heating, cooling, lighting and ventilation requirements of buildings--influencing 53% of building energy use. In particular, windows contribute significantly to the overall energy performance of building envelopes, thus there is a need to develop advanced energy efficient window and glazing systems. Electrochromic (EC) windows represent the next generation of advanced glazing technology that will (1) reduce the energy consumed in buildings, (2) improve the overall comfort of the building occupants, and (3) improve the thermal performance of the building envelope. ''Switchable'' EC windows provide, on demand, dynamic control of visible light, solar heat gain, and glare without blocking the view. As exterior light levels change, the window's performance can be electronically adjusted to suit conditions. A schematic illustrating how SageGlass{reg_sign} electrochromic windows work is shown in Figure I.1. SageGlass{reg_sign} EC glazings offer the potential to save cooling and lighting costs, with the added benefit of improving thermal and visual comfort. Control over solar heat gain will also result in the use of smaller HVAC equipment. If a step change in the energy efficiency and performance of buildings is to be achieved, there is a clear need to bring EC technology to the marketplace. This project addresses accelerating the widespread introduction of EC windows in buildings and thus maximizing total energy savings in the U.S. and worldwide. We report on R&D activities to improve the optical performance needed to broadly penetrate the full range of architectural markets. Also, processing enhancements have been implemented to reduce manufacturing costs. Finally, tests are being conducted to demonstrate the durability of the EC device and the dual pane insulating glass unit (IGU) to be at least equal to that of conventional windows.

  3. Electrophoretic Particle Guidance Significantly Enhances Olfactory Drug Delivery: A Feasibility Study

    PubMed Central

    Xi, Jinxiang; Si, Xiuhua A.; Gaide, Rachel

    2014-01-01

    Background Intranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and directly delivers medication to the brain and spinal cord. However, a device designed specifically for olfactory delivery has not yet been found. Methods In this study, a new delivery method was proposed that utilized electrophoretic forces to guide drug particles to the olfactory region. The feasibility of this method was numerically evaluated in both idealized 2-D and anatomically accurate 3-D nose models. The influence of nasal airflow, electrode strength, and drug release position were also studied on the olfactory delivery efficiency. Findings Results showed that by applying electrophoretic forces, the dosage to the olfactory region was significantly enhanced. In both 2-D and 3-D cases, electrophoretic-guided delivery achieved olfactory dosages nearly two orders of magnitude higher than that without electrophoretic forces. Furthermore, releasing drugs into the upper half of the nostril (i.e., partial release) led to olfactory dosages two times higher than releasing drugs over the entire area of the nostril. By combining the advantages of pointed drug release and appropriate electrophoretic guidance, olfactory dosages of more than 90% were observed as compared to the extremely low olfactory dosage (<1%) with conventional inhaler devices. Conclusion Results of this study have important implications in developing personalized olfactory delivery protocols for the treatment of neurological disorders. Moreover, a high sensitivity of olfactory dosage was observed in relation to different pointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery. PMID:24497957

  4. Clinical significance of late gadolinium enhancement in patients<20 years of age with hypertrophic cardiomyopathy.

    PubMed

    Smith, Brandon M; Dorfman, Adam L; Yu, Sunkyung; Russell, Mark W; Agarwal, Prachi P; Mahani, Maryam Ghadimi; Lu, Jimmy C

    2014-04-01

    Late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging is associated with adverse events in adults with hypertrophic cardiomyopathy (HC). However, limited data exist on the extent and clinical significance of LGE in the pediatric population. In 30 patients (aged 14.1±3.2 years) with clinically diagnosed HC who underwent cardiovascular magnetic resonance imaging from 2007 to 2012, segments with hypertrophy and LGE were identified by 2 experienced readers blinded to outcome. Radial, circumferential, and longitudinal strains were evaluated using feature tracking software. The composite outcome was defined as cardiac death, nonsustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter-defibrillator discharge. LGE was present in 17 of 30 patients (57%), all in a midmyocardial pattern, with median 3 segments per patient (interquartile range [IQR] 2 to 5). No LGE was detected in patients without phenotypic hypertrophy. Segments with LGE had decreased radial (basal segments 20.7% vs 70.9%, p=0.01), circumferential (basal segments -23.2% vs -29.3%, p=0.04), and longitudinal strains (basal segments -13.8% vs -20.9%, p=0.04). After median follow-up of 26.9 months (IQR 7.5 to 34.3), 7 patients who had an adverse outcome (5 ventricular tachycardia, 1 appropriate implantable cardioverter-defibrillator discharge, and 1 death) had more segments of LGE (median 4, IQR 2 to 7 vs 0, IQR 0 to 2, p=0.01). One patient without LGE had ventricular tachycardia on exercise test. In conclusion, LGE occurs in a similar pattern in pediatric patients with HC as in adults, associated with hypertrophy, decreased myocardial strain, and adverse clinical outcomes. Further longitudinal studies are necessary to evaluate the rate of development of LGE and relation to outcomes in a larger cohort. PMID:24513464

  5. The National Aeronautics and Space Administration's Earth Science Applications Program: Exploring Partnerships to Enhance Decision Making in Public Health Practice

    NASA Technical Reports Server (NTRS)

    Vann, Timi S.; Venezia, Robert A.

    2002-01-01

    The National Aeronautics and Space Administration (NASA), Earth Science Enterprise is engaged in applications of NASA Earth science and remote sensing technologies for public health. Efforts are focused on establishing partnerships with those agencies and organizations that have responsibility for protecting the Nation's Health. The program's goal is the integration of NASA's advanced data and technology for enhanced decision support in the areas of disease surveillance and environmental health. A focused applications program, based on understanding partner issues and requirements, has the potential to significantly contribute to more informed decision making in public health practice. This paper intends to provide background information on NASA's investment in public health and is a call for partnership with the larger practice community.

  6. HIV-1 Transgenic Rat Prefrontal Cortex Hyper-Excitability is Enhanced by Cocaine Self-Administration.

    PubMed

    Wayman, Wesley N; Chen, Lihua; Hu, Xiu-Ti; Napier, T Celeste

    2016-07-01

    The medial prefrontal cortex (mPFC) is dysregulated in HIV-1-infected humans and the dysregulation is enhanced by cocaine abuse. Understanding mPFC pathophysiology in this comorbid state has been hampered by the dearth of relevant animal models. To help fill this knowledge gap, electrophysiological assessments were made of mPFC pyramidal neurons (PN) from adult male HIV-1 transgenic (Tg) F344 rats (which express seven of the nine HIV-1 toxic proteins) and non-Tg F344 rats that self-administered cocaine for 14 days (COC-SA), as well as saline-yoked controls (SAL-Yoked) and experimentally naive Tg and non-Tg rats. Forebrain slices were harvested and prepared for whole-cell patch-clamp recording, and in treated rats, this occurred after 14-18 days of forced abstinence. Aged-matched rats were used for immunohistochemical detection of the L-channel protein, Cav1.2-α1c. We determined that: (i) the two genotypes acquired the operant task and maintained similar levels of COC-SA, (ii) forced abstinence from COC-SA enhanced mPFC PN excitability in both genotypes, and neurons from Tg rats exhibited the greatest pathophysiology, (iii) neurons from SAL-Yoked Tg rats were more excitable than those from SAL-Yoked non-Tg rats, and in Tg rats (iv) blockade of L-type Ca(2+) channels reduced the enhanced excitability, and (v) Cav1.2-immunoreactivity was increased. These findings provide the first assessment of the mPFC pathophysiology in a rodent model of HIV-1-mediated neuropathology with and without cocaine self-administration. Outcomes reveal an enhanced cortical excitability during chronic exposure to HIV-1 proteins that is excessively exacerbated with cocaine abuse. Such neuropathophysiology may underlie the cognitive dysregulation reported for comorbid humans. PMID:26677947

  7. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

    PubMed

    Sumi, H; Hamada, H; Nakanishi, K; Hiratani, H

    1990-01-01

    The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced. PMID:2123064

  8. THE ROLE OF OBSERVATION AND FEEDBACK IN ENHANCING PERFORMANCE WITH MEDICATION ADMINISTRATION.

    PubMed

    Davies, Karen; Mitchell, Charles; Coombes, Ian

    2015-12-01

    Legislation in Queensland such as the Health (Drugs and Poisons) Regulation 1996, the national registration competency standards set by the Nursing and Midwifery Board of Australia, and the Continuing Professional Development Registration Standards made pursuant to the Health Practitioner Regulation National Law define expected standards of practice for nurses. The Framework for Assessing Standards for Practice for Registered Nurses, Enrolled Nurses and Midwives, released in July 2015, includes the principles for assessing standards but not the methods. Local policies and procedures offer specific requirements founded on evidence-based practice. Observation of clinical practice with the provision of immediate descriptive feedback to individual practitioners has been associated with improved performance. This column describes the role of regular observation and individual feedback on medication administration as a strategy to enhance performance and patient care. PMID:26939498

  9. Allopregnanolone Elevations Following Pregnenolone Administration are Associated with Enhanced Activation of Emotion Regulation Neurocircuits

    PubMed Central

    Sripada, Rebecca K.; Marx, Christine E.; King, Anthony P.; Rampton, Jessica C.; Ho, Shaun; Liberzon, Israel

    2013-01-01

    Background The neurosteroid allopregnanolone is a potent allosteric modulator of the GABA(A) receptor with anxiolytic properties. Exogenous administration of allopregnanolone reduces anxiety, and allopregnanolone blockade impairs social and affective functioning. However, the neural mechanism whereby allopregnanolone improves mood and reduces anxiety is unknown. In particular, brain imaging has not been used to link neurosteroid effects to emotion regulation neurocircuitry. Methods To investigate the brain basis of allopregnanolone’s impact on emotion regulation, participants were administered 400mg of pregnenolone (N=16) or placebo (N=15) and underwent 3T fMRI while performing the Shifted-Attention Emotion Appraisal Task (SEAT), which probes emotional processing and regulation. Results Compared to placebo, allopregnanolone was associated with reduced activity in the amygdala and insula across all conditions. During the appraisal condition, allopregnanolone increased activity in the dorsal medial prefrontal cortex and enhanced connectivity between the amygdala and dorsal medial prefrontal cortex, an effect that was associated with reduced self-reported anxiety. Conclusions These results demonstrate that in response to emotional stimuli, allopregnanolone reduces activity in regions associated with generation of negative emotion. Furthermore, allopregnanolone may enhance activity in regions linked to regulatory processes. Aberrant activity in these regions has been linked to anxiety psychopathology. These results thus provide initial neuroimaging evidence that allopregnanolone may be a target for pharmacological intervention in the treatment of anxiety disorders, and suggest potential future directions for research into neurosteroid effects on emotion regulation neurocircuitry. PMID:23348009

  10. Annual committee reports on significant legislative, judicial and administrative developments in 1983: Public Lands and Land-Use Committee

    SciTech Connect

    Not Available

    1984-01-01

    The Supreme Court made three major land-use decisions during 1983, two dealing with federalism and the third with federal jiduciary obligation. The US Forest Service Small Tracts Act added flexibility to the disposal of small tracts. Court cases relating to national forests dealt with title disputes, oil and gas leasing, Indian religious practices, dual permitting under the Wilderness Act, and licensing hydro projects on Indian lands. The committee reports uneven administrative progress by the Forests Service in managing the forests. Legislation relating to Department of Interior Management Lands focuses on Outer Continental Shelf and federal coal leases and wilderness areas. The Supreme Court made several decisions involving the classification of sand and gravel as minerals, trespass, nonimpairment standards, herbicides, and other issues. 132 references.

  11. The intra-nasal administration of insulin induces significant hypoglycaemia and classical counterregulatory hormonal responses in normal man.

    PubMed

    Paquot, N; Scheen, A J; Franchimont, P; Lefebvre, P J

    1988-01-01

    The present study aimed at investigating the metabolic and hormonal consequences of intra-nasal administration of insulin in normal man. Lyophylisated regular porcine insulin (Insuline Ordinaire Organon) diluted with a non ionic detergent (Laureth-9 0,25%) was administered intra-nasally in 8 overnight fasted healthy volunteers using a calibrated aerosol delivery device (90 microliters = 9 U of insulin/spray) up to a total insulin dose close to 1 U/kg body weight. After intra-nasal insulin administration, plasma insulin levels rose from 5 +/- 1 to 38 +/- 10 mU/l (2p less than 0.01) at min 15, blood glucose concentrations decreased from 4.4 +/- 0.2 to 3.2 +/- 0.3 mmol/l (2p less than 0.01) at min 45, plasma C-peptide levels diminished from 327 +/- 31 to 174 +/- 28 mumol/l (2p less than 0.01) at min 60 and plasma free fatty acids concentrations fell from 336 +/- 109 to 130 +/- 31 mumol/l (2p less than 0.05) at min 30. The fall in blood glucose resulted in a prompt increase in plasma glucagon levels (from 78 +/- 28 to 150 +/- 24 ng/l at min 45; 2p less than 0.05) and in later rises in plasma growth hormone and cortisol concentrations. There was a close relationship between the individual maximal decreases in blood glucose levels and the individual maximal increases in plasma insulin (r = 0.81), glucagon (r = 0.88), cortisol (r = 0.87) and growth hormone (r = 0.76) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3292305

  12. In vivo estradiol production in postovulatory ovaries is enhanced by administration of testosterone but not by 5 alpha-dihydrotestosterone.

    PubMed

    Suzuki, K; Tamaoki, B

    1984-02-01

    Pre- and postovulatory states of ovaries were induced by the injection of PMSG and PMSG + hCG treatments, respectively, to immature rats. The concentration of ovarian estradiol measured by radioimmunoassay decreased significantly following hCG treatment to PMSG-pretreated rats. Subcutaneous administration of testosterone in soybean oil-glycerol mixture (9:1, v/v) restored the decreased concentration of the ovarian estradiol markedly in the PMSG + hCG treated rats, but not in the group treated with PMSG alone or in the control group treated with no gonadotropin. On the other hand, 5 alpha-dihydrotestosterone showed no increase in the ovarian estradiol of any group. When an ethanol solution of testosterone was administered s.c. to the PMSG + hCG treated rats, the ovarian estradiol level was maximally enhanced from 0.5 to 1.0 h after the injection. On the other hand, 5 alpha-dihydrotestosterone, dehydroepiandrosterone and 17 alpha-hydroxyprogesterone in ethanol showed no effect 1 h after the injection. These results indicate that the drastic decrease in ovarian estradiol production due to the hCG administration is caused by an acute decrease in the supply of aromatizable androgens to ovarian aromatase. PMID:6714511

  13. Significantly enhancing supercapacitive performance of nitrogen-doped graphene nanosheet electrodes by phosphoric acid activation.

    PubMed

    Wang, Ping; He, Haili; Xu, Xiaolong; Jin, Yongdong

    2014-02-12

    In this work, we present a new method to synthesize the phosphorus, nitrogen contained graphene nanosheets, which uses dicyandiamide to prevent the aggregation of graphene oxide and act as the nitrogen precursor, and phosphoric acid (H3PO4) as the activation reagent. We have found that through the H3PO4 activation, the samples exhibit the remarkably enhanced supercapacitive performance, and depending on the amount of H3PO4 introduced, the specific capacitance of the samples is gradually increased from 7.6 to 244.6 F g(-1). Meanwhile, the samples also exhibit the good rate capability and excellent stability (up to 10 000 cycles). Through the transmission electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Brunauer-Emmett-Teller analyses, H3PO4 treatment induced large pore volume and phosphorus related function groups in the product are assumed to response for the enhancement. PMID:24456232

  14. Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements

    PubMed Central

    Xing, Huaiyong; Zheng, Xiangpeng; Ren, Qingguo; Bu, Wenbo; Ge, Weiqiang; Xiao, Qingfeng; Zhang, Shengjian; Wei, Chenyang; Qu, Haiyun; Wang, Zheng; Hua, Yanqing; Zhou, Liangping; Peng, Weijun; Zhao, Kuaile; Shi, Jianlin

    2013-01-01

    The clinical potentials of radiotherapy could not be achieved completely because of the inaccurate positioning and inherent radioresistance of tumours. In this study, a novel active-targeting upconversion theranostic agent (arginine-glycine-aspartic acid-labelled BaYbF5: 2% Er3+ nanocube) was developed for the first time to address these clinical demands. Heavy metal-based nanocubes (~10 nm) are potential theranostic agents with bifunctional features: computed tomography (CT) contrast agents for targeted tumour imaging and irradiation dose enhancers in tumours during radiotherapy. Remarkably, they showed low toxicity and excellent performance in active-targeting CT imaging and CT imaging-guided radiosensitizing therapy, which could greatly concentrate and enlarge the irradiation dose deposition in tumours to enhance therapeutic efficacy and minimize the damage to surrounding tissues. PMID:23624542

  15. Image enhancement filters significantly improve reading performance for low vision observers

    NASA Technical Reports Server (NTRS)

    Lawton, T. B.

    1992-01-01

    As people age, so do their photoreceptors; many photoreceptors in central vision stop functioning when a person reaches their late sixties or early seventies. Low vision observers with losses in central vision, those with age-related maculopathies, were studied. Low vision observers no longer see high spatial frequencies, being unable to resolve fine edge detail. We developed image enhancement filters to compensate for the low vision observer's losses in contrast sensitivity to intermediate and high spatial frequencies. The filters work by boosting the amplitude of the less visible intermediate spatial frequencies. The lower spatial frequencies. These image enhancement filters not only reduce the magnification needed for reading by up to 70 percent, but they also increase the observer's reading speed by 2-4 times. A summary of this research is presented.

  16. Observation of Significant Quantum Efficiency Enhancement from a Polarized Photocathode with Distributed Bragg Reflector

    SciTech Connect

    Zhang, Shukui; Poelker, Matthew; Stutzman, Marcy L.; Chen, Yiqiao; Moy, Aaron

    2015-09-01

    Polarized photocathodes with higher Quantum efficiency (QE) would help to reduce the technological challenge associated with producing polarized beams at milliampere levels, because less laser light would be required, which simplifies photocathode cooling requirements. And for a given amount of available laser power, higher QE would extend the photogun operating lifetime. The distributed Bragg reflector (DBR) concept was proposed to enhance the QE of strained-superlattice photocathodes by increasing the absorption of the incident photons using a Fabry-Perot cavity formed between the front surface of the photocathode and the substrate that includes a DBR, without compromising electron polarization. Here we present recent results showing QE enhancement of a GaAs/GaAsP strained-superlattice photocathode made with a DBR structure. Typically, a GaAs/GaAsP strained-superlattice photocathode without DBR provides a QE of 1%, at a laser wavelength corresponding to peak polarization. In comparison, the GaAs/GaAsP strained-superlattice photocathodes with DBR exhibited an enhancement of over 2 when the incident laser wavelength was tuned to meet the resonant condition for the Fabry-Perot resonator.

  17. Significant Enhancement of H2 Formation in Disk Galaxies under Strong Ram Pressure

    NASA Astrophysics Data System (ADS)

    Henderson, Benjamin; Bekki, Kenji

    2016-05-01

    We show for the first time that H2 formation on dust grains can be enhanced in disk galaxies under strong ram pressure (RP). We numerically investigate how the time evolution of H i and H2 components in disk galaxies orbiting a group/cluster of galaxies can be influenced by the hydrodynamical interaction between the gaseous components of the galaxies and the hot intracluster medium. We find that compression of H i caused by RP increases H2 formation in disk galaxies before RP rapidly strips H i, cutting off the fuel supply and causing a drop in H2 density. We also find that the level of this H2 formation enhancement in a disk galaxy under RP depends on the mass of its host cluster dark matter halo, the initial positions and velocities of the disk galaxy, and the disk inclination angle with respect to the orbital plane. We demonstrate that dust growth is a key factor in the evolution of the H i and H2 mass in disk galaxies under strong RP. We discuss how the correlation between H2 fractions and surface gas densities of disk galaxies evolves with time in the galaxies under RP. We also discuss whether galaxy-wide star formation rates (SFRs) in cluster disk galaxies can be enhanced by RP if the SFRs depend on H2 densities.

  18. Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea.

    PubMed

    Chen, Jun; Jiang, Qiu-Dong; Wu, Ye-Ming; Liu, Pei; Yao, Jun-Hong; Lu, Qing; Zhang, Hui; Duan, Jin-Ao

    2015-01-01

    The present study was conducted to evaluate and compare five essential oils (EOs) as penetration enhancers (PEs) to improve the transdermal drug delivery (TDD) of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were identified by GC-MS. The corresponding cytotoxicities were evaluated in epidermal keartinocyte HaCaT cell lines by an MTT assay. Furthermore, the percutaneous permeation studies were carried out to compare the permeation enhancement effect of EOs. Then the therapeutic efficacy of ibuprofen with EOs was evaluated using dysmenorrheal model mice. The data supports a decreasing trend of skin cell viability in which Clove oil >Angelica oil > Chuanxiong oil > Cyperus oil > Cinnamon oil > Azone. Chuanxiong oil and Angelica oil had been proved to possess a significant permeation enhancement for TDD of ibuprofen. More importantly, the pain inhibitory intensity of ibuprofen hydrogel was demonstrated to be greater with Chuanxiong oil when compared to ibuprofen without EOs (p < 0.05). The contents of calcium ion and nitric oxide (NO) were also significantly changed after the addition of Chuanxiong oil (p < 0.05). In summary, we suggest that Chuanxiong oil should be viewed as the best PE for TDD of ibuprofen to treat dysmenorrhea. PMID:26457698

  19. Administrators' Perceptions of Factors Related to Student Retention at Colleges with a Significant Black Student Enrollment Affiliated with the Association for Biblical Higher Education

    ERIC Educational Resources Information Center

    Wilson, Wesley B.

    2013-01-01

    This study described and explored the factors perceived as relevant to student retention by administrators at colleges and universities with significant Black student populations. The sample was 31 institutions affiliated with the Association for Biblical Higher Education (ABHE) that had Black student enrollment of 20% or more. The study sought to…

  20. From 9/11 to Recession: Historically Significant Events in America and Their Impact on Research Administration

    ERIC Educational Resources Information Center

    Minnema, Linnea

    2011-01-01

    Federally sponsored research funding sources are not stagnant programs. Many things influence the nature of research, not all of them purely scientific. Historically significant events draw public attention to causes, and in the age of immediate information those events can have a powerful and lasting impact on research funding. September 11, 2001…

  1. Hydrostatic pressure: a very effective approach to significantly enhance critical current density in granular iron pnictide superconductors.

    PubMed

    Shabbir, Babar; Wang, Xiaolin; Ghorbani, S R; Shekhar, Chandra; Dou, Shixue; Srivastava, O N

    2015-01-01

    Pressure is well known to significantly raise the superconducting transition temperature, Tc, in both iron pnictides and cuprate based superconductors. Little work has been done, however, on how pressure can affect the flux pinning and critical current density in the Fe-based superconductors. Here, we propose to use hydrostatic pressure to significantly enhance flux pinning and Tc in polycrystalline pnictide bulks. We have chosen Sr4V2O6Fe2As2 polycrystalline samples as a case study. We demonstrate that the hydrostatic pressure up to 1.2 GPa can not only significantly increase Tc from 15 K (underdoped) to 22 K, but also significantly enhance the irreversibility field, Hirr, by a factor of 4 at 7 K, as well as the critical current density, Jc, by up to 30 times at both low and high fields. It was found that pressure can induce more point defects, which are mainly responsible for the Jc enhancement. Our findings provide an effective method to significantly enhance Tc, Jc, Hirr, and the upper critical field, Hc2, for other families of Fe-based superconductors in the forms of wires/tapes, films, and single crystal and polycrystalline bulks. PMID:25645351

  2. Hydrostatic pressure: A very effective approach to significantly enhance critical current density in granular iron pnictide superconductors

    PubMed Central

    Shabbir, Babar; Wang, Xiaolin; Ghorbani, S. R.; Shekhar, Chandra; Dou, Shixue; Srivastava, O. N.

    2015-01-01

    Pressure is well known to significantly raise the superconducting transition temperature, Tc, in both iron pnictides and cuprate based superconductors. Little work has been done, however, on how pressure can affect the flux pinning and critical current density in the Fe-based superconductors. Here, we propose to use hydrostatic pressure to significantly enhance flux pinning and Tc in polycrystalline pnictide bulks. We have chosen Sr4V2O6Fe2As2 polycrystalline samples as a case study. We demonstrate that the hydrostatic pressure up to 1.2 GPa can not only significantly increase Tc from 15 K (underdoped) to 22 K, but also significantly enhance the irreversibility field, Hirr, by a factor of 4 at 7 K, as well as the critical current density, Jc, by up to 30 times at both low and high fields. It was found that pressure can induce more point defects, which are mainly responsible for the Jc enhancement. Our findings provide an effective method to significantly enhance Tc, Jc, Hirr, and the upper critical field, Hc2, for other families of Fe-based superconductors in the forms of wires/tapes, films, and single crystal and polycrystalline bulks. PMID:25645351

  3. [Expression and Clinical Significance of Lymphoid Enhancer-Binding Factor 1 in Acute Leukemias].

    PubMed

    Huo, Wan-Ying; Gao, Ju

    2015-06-01

    Lymphoid enhancer-binding factor 1 (LEF1), a key downstream effector of Wnt/β-catenin signal transduction pathway, plays a crucial role in the maintenance, proliferation and differentiation of normal hematopoietic stem/progenitor cells through regulating the transcription of its target genes. Aberrant LEF1 expression has been documented in a variety of leukemias, and implicated in the prediction of prognosis. Nevertheless, discrepancies exist regarding the expression level and clinical implication of LEF1 in different types of leukemias, suggesting LEF1 might exert distinct roles in different types of leukemia. In the present article, recent research advances of the relationship of LEF1 and regulation of hematopoiesis and leukemogenesis are reviewed. PMID:26117056

  4. Tyrosine administration enhances dopamine synthesis and release in light-activated rat retina

    NASA Technical Reports Server (NTRS)

    Gibson, C. J.; Watkins, C. J.; Wurtman, R. J.

    1983-01-01

    Exposure of dark-adapted albino rats to light (350 lux) significantly elevated retinal levels of the dopamine metabolite dihydroxyphenyl acetic acid during the next hour; their return to a dark environment caused dihydroxyphenyl acetic acid levels to fall. Retinal dopamine levels were increased slightly by light exposure, suggesting that the increase in dihydroxyphenyl acetic acid reflected accelerated dopamine synthesis. Administration of tyrosine (100 mg/kg, i.p.) further elevated retinal dihydroxyphenyl acetic acid among light-exposed animals, but failed to affect dopamine release among animals in the dark. These observations show that a physiological stimulus - light exposure - can cause catecholaminergic neurons to become tyrosine-dependent; they also suggest that food consumption may affect neurotransmitter release within the retina.

  5. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels

    PubMed Central

    Fujisawa, Naoaki; Mori, Harushi; Matsui, Toru

    2015-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to experience numbness in all fingers of his left hand one year ago, which gradually extended to his body trunk and legs on both sides. Magnetic resonance imaging demonstrated numerous small enhancing spots scattered in his brain and spinal cord. CSF levels of β-2 microglobulin were elevated; although this often indicates central nervous system involvement in leukemia and lymphoma, the lesions were diagnosed as CLIPPERS based on the pathological findings from a biopsy specimen. We emphasize the importance of biopsy to differentiate between CLIPPERS and malignant lymphoma because the temporary radiological response to steroid might be the same in both diseases but the treatment strategies regarding the use of steroid are quite different. PMID:26713153

  6. Administration of cells with thermosensitive hydrogel enhances the functional recovery in ischemic rat heart

    PubMed Central

    Matsushita, Satoshi; Forrester, James S; Li, Chuan; Sato, Mitsuru; Li, Zhengqing; Guo, Xiaolei; Guan, Jianjun; Amano, Atsushi

    2016-01-01

    The lack of cell retention clearly represents a potentially serious limitation for therapeutic efficacy of stem cells. To enhance the efficacy, we developed a novel hydrogel that is thermosensitive and biodegradable and possesses desirable stiffness in a solid form. Immediately after induction of myocardial infarction of male rat, cardiac outgrowth cells embedded in hydrogel (HG) or saline (CO) were injected directly into the peri-infarct area. Left ventricular ejection fraction, cell retention rate, and a spectrum of biochemical markers were measured to evaluate the effect of the treatment. Left ventricular ejection fraction was significantly higher in the cell-injected groups (HG and CO) than in the control group at 1 week after treatment. This functional benefit was continued only in the HG group, accompanied with more retained cells. Furthermore, the expression of insulin-like growth factor-1 was significantly higher in the HG group with less progression of cell apoptosis. PMID:27213036

  7. MEETING REPORT: OMG Technical Committee Meeting in Orlando, FL, sees significant enhancement to CORBA

    NASA Astrophysics Data System (ADS)

    1998-06-01

    The Object Management Group (OMG) Platform Technology Committee (PTC) ratified its support for a new asynchronous messaging service for CORBA at OMG's recent Technical Committee Meeting in Orlando, FL. The meeting, held from 8 - 12 June, saw the PTC send the Messaging Service out for a final vote among the OMG membership. The Messaging Service, which will integrate Message Oriented Middleware (MOM) with CORBA, will give CORBA a true asynchronous messaging capability - something of great interest to users and developers. Formal adoption of the specification will most likely occur by the end of the year. The Messaging Service The Messaging Service, when adopted, will be the world's first standard for Message Oriented Middleware and will give CORBA a true asynchronous messaging capability. Asynchronous messaging allows developers to build simpler, richer client environments. With asynchronous messaging there is less need for multi-threaded clients because the Asynchronous Method Invocation is non-blocking, meaning the client thread can continue work while the application waits for a reply. David Curtis, Director of Platform Technology for OMG, said: `This messaging service is one of the more valuable additions to CORBA. It enhances CORBA's existing asynchronous messaging capabilities which is a feature of many popular message oriented middleware products. This service will allow better integration between ORBs and MOM products. This enhanced messaging capability will only make CORBA more valuable for builders of distributed object systems.' The Messaging Service is one of sixteen technologies currently being worked on by the PTC. Additionally, seventeen Revision Task Forces (RTFs) are working on keeping OMG specifications up to date. The purpose of these Revision Task Forces is to take input from the implementors of OMG specifications and clarify or make necessary changes based on the implementor's input. The RTFs also ensure that the specifications remain up to date

  8. Reoxygenation of Asphyxiated Newborn Piglets: Administration of 100% Oxygen Causes Significantly Higher Apoptosis in Cortical Neurons, as Compared to 21%

    PubMed Central

    Faa, G.; Fanos, V.; Fanni, D.; Gerosa, C.; Faa, A.; Fraschini, M.; Pais, M. E.; Di Felice, E.; Papalois, A.; Varsami, M.; Xanthos, T.; Iacovidou, N.

    2014-01-01

    Objective. Evaluation of neuronal changes in an animal experimental model of normocapnic hypoxia- reoxygenation. Materials and Methods. Fifty male piglets were the study subjects; normocapnic hypoxia was induced in 40 piglets and ten were sham-operated (controls). When bradycardia and/or severe hypotension occurred, reoxygenation was initiated. Animals were allocated in 4 groups according to the oxygen concentration, they were resuscitated with 18%, 21%, 40%, and 100% O2. Persisting asystole despite 10 minutes of cardiopulmonary resuscitation and return of spontaneous circulation were the endpoints of the experiment. Surviving animals were euthanized and brain cortex samples were collected, hematoxylin and eosin-stained, and examined for apoptotic bodies observing 10 consecutive high power fields. Results. Histological examination of the control group did not show any pathological change. On the contrary, apoptosis of neurons was found in 87.5% of treated animals. When specimens were examined according to the oxygen concentration used for resuscitation, we found marked intergroup variability; a higher percentage of apoptotic neurons was observed in piglets of group 4 (100% oxygen) compared to the others (P = 0.001). Conclusions. This preliminary data shows that normocapnic hypoxia and reoxygenation in Landrace/Large White piglets resulted in significant histological changes in the brain cortex. The degree of pathological changes in cortical neurons was significantly associated with the oxygen concentration used for reoxygenation, with a higher percentage of apoptotic neurons being observed in piglets reoxygenated with 100% compared to 18% O2 and to 21% O2. PMID:24783208

  9. Roxarsone and its metabolites in chicken manure significantly enhance the uptake of As species by vegetables.

    PubMed

    Huang, Lianxi; Yao, Lixian; He, Zhaohuan; Zhou, Changmin; Li, Guoliang; Yang, Baomei; Deng, Xiancai

    2014-04-01

    Roxarsone is an organoarsenic feed additive which can be finally degraded to other higher toxic metabolites after excreted by animal. In this work, the uptake of As species by vegetables treated with chicken manure bearing roxarsone and its metabolites was investigated. It was showed that more than 96% of roxarsone added in chicken feed was degraded and converted to arsenite, monomethylarsonic acid, dimethylarsinic acid, arsenate, 4-hydroxyphenylarsonic acid and other unknown As species. Arsenite and arsenate could be found in roots of vegetables but only arsenite transported up to shoots. Chicken manure bearing roxarsone and its metabolites increased 33-175% of arsenite and 28% ∼ seven times of arsenate in vegetable roots, 68-175% of arsenite in edible vegetable shoots. Arsenite, the most toxic As form, was the major extractable As species in vegetables accounted for 79-98%. The results reflected that toxic element As could be absorbed by vegetables via the way: roxarsone in feed → animal → animal manure → soil → crop and the uptake of As species would be enhanced by using chicken manure bearing roxarsone and its metabolites as organic fertilizer. PMID:24461427

  10. Tuning to the significant: neural and genetic processes underlying affective enhancement of visual perception and memory.

    PubMed

    Markovic, Jelena; Anderson, Adam K; Todd, Rebecca M

    2014-02-01

    Emotionally arousing events reach awareness more easily and evoke greater visual cortex activation than more mundane events. Recent studies have shown that they are also perceived more vividly and that emotionally enhanced perceptual vividness predicts memory vividness. We propose that affect-biased attention (ABA) - selective attention to emotionally salient events - is an endogenous attentional system tuned by an individual's history of reward and punishment. We present the Biased Attention via Norepinephrine (BANE) model, which unifies genetic, neuromodulatory, neural and behavioural evidence to account for ABA. We review evidence supporting BANE's proposal that a key mechanism of ABA is locus coeruleus-norepinephrine (LC-NE) activity, which interacts with activity in hubs of affective salience networks to modulate visual cortex activation and heighten the subjective vividness of emotionally salient stimuli. We further review literature on biased competition and look at initial evidence for its potential as a neural mechanism behind ABA. We also review evidence supporting the role of the LC-NE system as a driving force of ABA. Finally, we review individual differences in ABA and memory including differences in sensitivity to stimulus category and valence. We focus on differences arising from a variant of the ADRA2b gene, which codes for the alpha2b adrenoreceptor as a way of investigating influences of NE availability on ABA in humans. PMID:24269973

  11. Research to Significantly Enhance Composites Survivability at 550 F in Oxidative Environments

    NASA Technical Reports Server (NTRS)

    Meador, Michael A. (Technical Monitor); Guinn, L.; Tewoldeberhan, A.; Inkurnsah, M.; Makori, F.; Carty, A.; Carson, L.

    2003-01-01

    Methylene dianiline (MDA) and its derivatives have been used in the synthesis of polyimides to yield polymers with characteristic low-density, high tensile strength, improved solubility in organic solvents, low-melt viscosities and high thermal stability (greater than 550 F) in air. Polyimides with such properties are desirable for use in aerospace systems, e.g., jet engines, airframe, missiles, and rockets where weight is critical. Recent research at Prairie View A&M University is focused on developing monomers to generate polyimides with enhanced performance over that of NASA s PMR-15. The objective of this work is to synthesize three ring aromatic diamines which are non-toxic and when reacted with the appropriate dianhydrides will yield polyimides with lower viscosity, improve processability, good retention of mechanical properties, and oxidative stability at high environmental temperatures. Modifications of the three ring aromatic diamines include replacing the methylene linkages with aromatic ethers by nucleophilic aromatic substitution reactions and incorporating mono- and di-substituents to the center aromatic ring. An update of current reactions involved in synthesis efforts to generate three ring aromatic monomers for polyimides with methylene, carbonyl, and ether linkages separating the aromatic moieties will be displayed.

  12. The significant adhesion enhancement of Ag-polytetrafluoroethylene antibacterial coatings by using of molecular bridge

    NASA Astrophysics Data System (ADS)

    Guo, Ruijie; Yin, Guangda; Sha, Xiaojuan; Zhao, Qi; Wei, Liqiao; Wang, Huifang

    2015-06-01

    Weak adhesion between the metal-based antibacterial coatings and polymer substrates limits their clinical applications; surface modification is an effective way to solve this intrinsic problem. In this study, UV irradiation was employed to activate the inert silicon rubber substrates, and the grafting of coupling agent (3-mercaptopropyl) trimethoxy silane into the UV-irradiated substrates generated reactive surface containing sbnd SH groups. During electroless plating S which has lone pair electrons anchored Ag+ and produced antibacterial coatings with improved adhesion. The grafting of (3-mercaptopropyl) trimethoxy silane into silicon rubber was verified by X-ray photoelectron spectroscopy (XPS). The adhesion was tested by American Society of Testing Materials (ASTM D 3359-02). Surface elements content and distribution were observed and analyzed by X-ray energy disperse spectroscopy (EDS). The antibacterial performance was characterized by inhibition halo test and shake flash method. The results showed that the as-prepared composite Ag-polytetrafluoroethylene coatings possessed remarkably enhanced adhesion and superior antibacterial activity.

  13. Significant enhancement of the thermoelectric figure of merit of polycrystalline Si films by reducing grain size

    NASA Astrophysics Data System (ADS)

    Valalaki, K.; Vouroutzis, N.; Nassiopoulou, A. G.

    2016-08-01

    The thermoelectric properties of p-type polycrystalline silicon thin films deposited by low pressure chemical vapour deposition (LPCVD) were accurately determined at room temperature and the thermoelectric figure of merit was deduced as a function of film thickness, ranging from 100 to 500 nm. The effect of film thickness on their thermoelectric performance is discussed. More than threefold increase in the thermoelectric figure of merit of the 100 nm thick polysilicon film was observed compared to the 500 nm thick film, reaching a value as high as 0.033. This enhancement is mainly the result of the smaller grain size in the thinner films. With the decrease in grain size the resistivity of the films is increased twofold and electrical conductivity decreased, however the Seebeck coefficient is increased by 30% and the thermal conductivity is decreased eightfold, being mainly at the origin of the increased figure of merit of the 100 nm film. Our experimental results were compared to known theoretical models and the possible mechanisms involved are presented and discussed.

  14. Simple Machine Perfusion Significantly Enhances Hepatocyte Yields of Ischemic and Fresh Rat Livers

    PubMed Central

    Izamis, Maria-Louisa; Calhoun, Candice; Uygun, Basak E.; Guzzardi, Maria Angela; Price, Gavrielle; Luitje, Martha; Saeidi, Nima; Yarmush, Martin L.; Uygun, Korkut

    2013-01-01

    The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3-h room temperature (20 ± 2°C) machine perfusion protocol to treat nonpremedicated livers exposed to 1 h of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated, and untreated ischemic livers using viable hepatocyte yields and in vitro performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Furthermore, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized. PMID:25431743

  15. Oral Administration of Blueberry Inhibits Angiogenic Tumor Growth and Enhances Survival of Mice with Endothelial Cell Neoplasm

    PubMed Central

    Fang, Huiqing; Khanna, Savita; Harper, Justin; Phillips, Gary; Sen, Chandan K.

    2009-01-01

    Abstract Endothelial cell neoplasms are the most common soft tissue tumor in infants. Subcutaneous injection of spontaneously transformed murine endothelial (EOMA) cells results in development of hemangioendothelioma (HE). We have previously shown that blueberry extract (BBE) treatment of EOMA cells in vitro prior to injection in vivo can significantly inhibit the incidence and size of developing HE. In this study, we sought to determine whether oral BBE could be effective in managing HE and to investigate the mechanisms through which BBE exerts its effects on endothelial cells. A dose-dependent decrease in HE tumor size was observed in mice receiving daily oral gavage feeds of BBE. Kaplan-Meier survival curve showed significantly enhanced survival for mice with HE tumors given BBE, compared to control. BBE treatment of EOMA cells inhibited both c-Jun N-terminal kinase (JNK) and NF-κB signaling pathways that culminate in monocyte chemoattractant protein-1 (MCP-1) expression required for HE development. Antiangiogenic effects of BBE on EOMA cells included decreased proliferation by BrdU assay, decreased sprouting on Matrigel, and decreased transwell migration. Thus, this work provides first evidence demonstrating that BBE can limit tumor formation through antiangiogenic effects and inhibition of JNK and NF-κB signaling pathways. Oral administration of BBE represents a potential therapeutic antiangiogenic strategy for treating endothelial cell neoplasms in children. Antioxid Redox Signal 11, 47–58. PMID:18817478

  16. FOCUSED R&D FOR ELECTROCHROMIC SMART WINDOWS: SIGNIFICANT PERFORMANCE AND YIELD ENHANCEMENTS

    SciTech Connect

    Marcus Milling

    2004-09-23

    Developments made under this program will play a key role in underpinning the technology for producing EC devices. It is anticipated that the work begun during this period will continue to improve materials properties, and drive yields up and costs down, increase durability and make manufacture simpler and more cost effective. It is hoped that this will contribute to a successful and profitable industry, which will help reduce energy consumption and improve comfort for building occupants worldwide. The first major task involved improvements to the materials used in the process. The improvements made as a result of the work done during this project have contributed to the enhanced performance, including dynamic range, uniformity and electrical characteristics. Another major objective of the project was to develop technology to improve yield, reduce cost, and facilitate manufacturing of EC products. Improvements directly attributable to the work carried out as part of this project and seen in the overall EC device performance, have been accompanied by an improvement in the repeatability and consistency of the production process. Innovative test facilities for characterizing devices in a timely and well-defined manner have been developed. The equipment has been designed in such a way as to make scaling-up to accommodate higher throughput necessary for manufacturing relatively straightforward. Finally, the third major goal was to assure the durability of the EC product, both by developments aimed at improving the product performance, as well as development of novel procedures to test the durability of this new product. Both aspects have been demonstrated, both by carrying out a number of different durability tests, both in-house and by independent third-party testers, and also developing several novel durability tests.

  17. Evaluating research for clinical significance: using critically appraised topics to enhance evidence-based neuropsychology.

    PubMed

    Bowden, Stephen C; Harrison, Elise J; Loring, David W

    2014-01-01

    Meehl's (1973, Psychodiagnosis: Selected papers. Minneapolis: University of Minnesota Press) distinction between statistical and clinical significance holds special relevance for evidence-based neuropsychological practice. Meehl argued that despite attaining statistical significance, many published findings have limited practical value since they do not inform clinical care. In the context of an ever expanding clinical research literature, accessible methods to evaluate clinical impact are needed. The method of Critically Appraised Topics (Straus, Richardson, Glasziou, & Haynes, 2011, Evidence-based medicine: How to practice and teach EBM (4th ed.). Edinburgh: Elsevier Churchill-Livingstone) was developed to provide clinicians with a "toolkit" to facilitate implementation of evidence-based practice. We illustrate the Critically Appraised Topics method using a dementia screening example. We argue that the skills practiced through critical appraisal provide clinicians with methods to: (1) evaluate the clinical relevance of new or unfamiliar research findings with a focus on patient benefit, (2) help focus of research quality, and (3) incorporate evaluation of clinical impact into educational and professional development activities. PMID:23463942

  18. Delayed Administration of Bone Marrow Mesenchymal Stem Cell Conditioned Medium Significantly Improves Outcome After Retinal Ischemia in Rats

    PubMed Central

    Dreixler, John C.; Poston, Jacqueline N.; Balyasnikova, Irina; Shaikh, Afzhal R.; Tupper, Kelsey Y.; Conway, Sineadh; Boddapati, Venkat; Marcet, Marcus M.; Lesniak, Maciej S.; Roth, Steven

    2014-01-01

    Purpose. Delayed treatment after ischemia is often unsatisfactory. We hypothesized that injection of bone marrow stem cell (BMSC) conditioned medium after ischemia could rescue ischemic retina, and in this study we characterized the functional and histological outcomes and mechanisms of this neuroprotection. Methods. Retinal ischemia was produced in adult Wistar rats by increasing intraocular pressure for 55 minutes. Conditioned medium (CM) from rat BMSCs or unconditioned medium (uCM) was injected into the vitreous 24 hours after the end of ischemia. Recovery was assessed 7 days after ischemia using electroretinography, at which time we euthanized the animals and then prepared 4-μm-thick paraffin-embedded retinal sections. TUNEL and Western blot were used to identify apoptotic cells and apoptosis-related gene expression 24 hours after injections; that is, 48 hours after ischemia. Protein content in CM versus uCM was studied using tandem mass spectrometry, and bioinformatics methods were used to model protein interactions. Results. Intravitreal injection of CM 24 hours after ischemia significantly improved retinal function and attenuated cell loss in the retinal ganglion cell layer. CM attenuated postischemic apoptosis and apoptosis-related gene expression. By spectral counting, 19 proteins that met stringent identification criteria were increased in the CM compared to uCM; the majority were extracellular matrix proteins that mapped into an interactional network together with other proteins involved in cell growth and adhesion. Conclusions. By restoring retinal function, attenuating apoptosis, and preventing retinal cell loss after ischemia, CM is a robust means of delayed postischemic intervention. We identified some potential candidate proteins for this effect. PMID:24699381

  19. The incidence and significance of acute kidney injury following emergent contrast administration in patients with STEMI and stroke.

    PubMed

    Marchick, Michael Robert; Allen, Brandon Russell; Weeks, Emily Cassin; Shuster, Jonathan Jacob; Elie, Marie-Carmelle

    2016-09-01

    The authors have investigated the incidence of acute kidney injury (AKI) and short-term mortality following an activated STEMI and stroke alert at a tertiary referral and academic center. A single center, retrospective chart review of STEMI and stroke activation patients from January 2010 to March 2012. Data was collected and reviewed from an institutional database following IRB-approval. Inclusion criteria were STEMI patients taken for cardiac catheterization, excluding patients receiving hemodialysis due to end-stage renal disease (ESRD). Primary outcome measures were the incidence of AKI using the RIFLE criteria and short-term mortality. 745 patients were included (488 stroke, 257 STEMI). The median age was 65, and 39 % were female. Overall inpatient mortality was 7.0 %. 5.4 % (40/745) of patients experienced some degree of AKI (8.6 % of STEMI, 3.7 % of stroke patients). Overall, 30 % of patients with AKI died during their hospitalization. AKI was associated with a 7.1-fold (95 % CI 3.4-15.1) increase in mortality in the entire cohort. Among STEMI patients, AKI was associated with a 66.6-fold (95 % CI 12.9-343.4) increase in mortality. These findings follow similar trends published among critically ill patients with AKI. The risk of death with concomitant AKI in this hospital population is significant and deserves future study. Early recognition and awareness in the emergency department is paramount to the patient's survival. Future studies should focus on modalities to improve early recognition and preventative therapies. PMID:26910240

  20. An enhanced cluster analysis program with bootstrap significance testing for ecological community analysis

    USGS Publications Warehouse

    McKenna, J.E., Jr.

    2003-01-01

    The biosphere is filled with complex living patterns and important questions about biodiversity and community and ecosystem ecology are concerned with structure and function of multispecies systems that are responsible for those patterns. Cluster analysis identifies discrete groups within multivariate data and is an effective method of coping with these complexities, but often suffers from subjective identification of groups. The bootstrap testing method greatly improves objective significance determination for cluster analysis. The BOOTCLUS program makes cluster analysis that reliably identifies real patterns within a data set more accessible and easier to use than previously available programs. A variety of analysis options and rapid re-analysis provide a means to quickly evaluate several aspects of a data set. Interpretation is influenced by sampling design and a priori designation of samples into replicate groups, and ultimately relies on the researcher's knowledge of the organisms and their environment. However, the BOOTCLUS program provides reliable, objectively determined groupings of multivariate data.

  1. Mutation of Escherichia coli cytosine deaminase significantly enhances molecular chemotherapy of human glioma.

    PubMed

    Kaliberov, S A; Market, J M; Gillespie, G Y; Krendelchtchikova, V; Della Manna, D; Sellers, J C; Kaliberova, L N; Black, M E; Buchsbaum, D J

    2007-07-01

    Combined treatment using adenoviral (Ad)-directed enzyme/prodrug therapy and radiation therapy has the potential to become a powerful method of cancer therapy. We have developed an Ad vector encoding a mutant bacterial cytosine deaminase (bCD) gene (AdbCD-D314A), which has a higher affinity for cytosine than wild-type bCD (bCDwt). The purpose of this study was to evaluate cytotoxicity in vitro and therapeutic efficacy in vivo of the combination of AdbCD-D314A with the prodrug 5-fluorocytosine (5-FC) and ionizing radiation against human glioma. The present study demonstrates that AdbCD-D314A infection resulted in increased 5-FC-mediated cell killing, compared with AdbCDwt. Furthermore, a significant increase in cytotoxicity following AdbCD-D314A and radiation treatment of glioma cells in vitro was demonstrated as compared to AdbCDwt. Animal studies showed significant inhibition of subcutaneous or intracranial tumor growth of D54MG glioma xenografts by the combination of AdbCD-D314A/5-FC with ionizing radiation as compared with either agent alone, and with AdbCDwt/5-FC plus radiation. The results suggest that the combination of AdbCD-D314A/5-FC with radiation produces markedly increased cytotoxic effects in cancer cells in vitro and in vivo. These data indicate that combined treatment with this novel mutant enzyme/prodrug therapy and radiotherapy provides a promising approach for cancer therapy. PMID:17495948

  2. Failure of Immune Sera to Enhance Significantly Phagocytosis of Staphylococus aureus: Nonspecific Adsorption of Phagocytosis-Promoting Factors

    PubMed Central

    Shayegani, Mehdi

    1970-01-01

    Serum from rabbits immunized with either heat-killed or live nonencapsulated Staphylococcus aureus failed further to enhance phagocytosis and intracellular killing of the homologous organism by either normal rabbit polymorphonuclear leukocytes or monocytes, when compared with normal rabbit serum. These immune sera did, however, show an increase in agglutinating and precipitating antibody level. Adsorption of normal human serum with some gram-positive and gram-negative bacteria, yeast, and some inert particles significantly reduced the phagocytosis-promoting factors of the serum. It would seem, then, that nonencapsulated S. aureus differs from other pathogenic bacteria in that the humoral antibacterial factors promoting its phagocytosis and intracellular killing are not significantly enhanced by infection or immunization. PMID:16557910

  3. Prophylactic administration of topical glutamine enhances the capability of the rat colon to resist inflammatory damage.

    PubMed

    Israeli, Eran; Berenshtein, Eduard; Wengrower, Dov; Aptekar, Larisa; Kohen, Ron; Zajicek, Gershom; Goldin, Eran

    2004-10-01

    Glutamine is an important nutrient for the GI tract and has been shown to exert a protective effect on the bowel. Nonetheless, in the context of IBD, data demonstrating a therapeutic role for glutamine has been inconclusive. IBD is associated with oxidative stress caused by reactive oxygen species. We aimed to investigate the effect of topical glutamine administration in rats before or after induction of colitis by trinitrobenzenosulfonic acid. In study I glutamine enemas were given beginning 2 days before or on the same day of induction of colitis. Inflammation severity was assessed by macroscopic and microscopic score and tissue myeloperoxidase activity. In study II glutamine enemas were given for 3 days without induction of colitis: mitotic index and colonic crypt length were measured, as well as water-soluble low molecular weight antioxidants and energy-rich phosphate levels (by HPLC). Results showed that glutamine significantly decreased indexes of inflammation when administered before induction of colitis. Glutamine caused an increase in the mitotic index and the levels of water-soluble low molecular weight antioxidants and energy-rich phosphates. We conclude that glutamine exerts a beneficial effect only when administered before induction of colitis, by increasing the resistance of the colonic tissue to inflammatory injury. This effect is probably mediated by increasing the antioxidant capacity and energy level of the tissue. PMID:15573931

  4. Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

    PubMed

    Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

    2016-04-01

    The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs. PMID:26871003

  5. Administration of yeast glucan enhances survival and some non-specific and specific immune parameters in carp (Cyprinus carpio) infected with Aeromonas hydrophila.

    PubMed

    Selvaraj, V; Sampath, K; Sekar, V

    2005-10-01

    Effects of beta-glucan administration on survival and immune modulations were studied in Cyprinus carpio against the bacterial pathogen, Aeromonas hydrophila. Beta-glucan was extracted from Saccharomyces cervisiae and purified. A virulent strain of the pathogen A. hydrophila was collected from infected fish. Different concentrations of beta-glucan were administered to test animals on day 1, 3 and 5 through different routes (intraperitoneal injection (ip), bathing and oral administration). Control and test animals were challenged by ip injection of LD50 concentration of A. hydrophila on day 7 and mortality was observed and Relative Percent Survival (RPS) was calculated. Intraperitoneal injection of 500 microg of glucan significantly enhanced the RPS; bathing and oral administration of glucan did not influence the RPS. On day 7, test animals injected with 100, 500 and 1000 microg of glucan had a significant increase in total blood leucocyte counts and an increase in the proportion of neutrophils and monocytes. Superoxide anion production by kidney macrophages was also elevated. RT-PCR and northern blot analysis of interleukin-1 mRNA showed elevated expression in kidney on day 7 in fish injected with glucan. Glucan had an adjuvant effect on antibody production as pretreatment by injection of 100-1000 microg glucan/fish resulted in the highest antibody titer against A. hydrophila following vaccination. Classical and alternative complement pathways were not affected by glucan administration by any of the three routes. PMID:15863011

  6. Melatonin administration enhances the reproductive capacity of young rams under a southern Mediterranean environment.

    PubMed

    Rekik, Mourad; Taboubi, Rahma; Ben Salem, Imene; Fehri, Younes; Sakly, Cyrine; Lassoued, Narjess; Hilali, Muhi Eddine

    2015-07-01

    This study tested the effect of melatonin treatment, initiated in late February on reproductive traits of young rams. A total of 14 young Barbarine rams were used. Seven animals were treated with three melatonin subcutaneous implants (Melatonin) on 28 February while the remaining rams remained untreated (Control). After 60 days of melatonin administration, scrotal circumference reached average values of 32.1 ± 1.54 and 29.5 ± 1.0 cm for Melatonin and Control animals, respectively (P < 0.05). Semen characteristics did not differ between groups; melatonin treatment tended (P = 0.091) to increase sperm concentration 60 days after implantation when means reached 5.87 ± 0.703 and 4.61 ± 0.654 × 10(9) spermatozoa/mL for Melatonin and Control rams, respectively. Melatonin treatment significantly affected total activity time, number of lateral approaches and mount attempts in comparison to controls. During a 6-h sampling period, mean plasma testosterone concentrations increased as a result of melatonin treatment (P < 0.001) and testosterone pulse frequency averaged 3.45 ± 2.24 and 1.25 ± 1.0 (P = 0.086) for Melatonin and Control rams. Data clearly suggest that abrupt treatment of young rams with melatonin implants in winter is sufficient to improve reproductive traits. PMID:25689168

  7. Enhanced elimination of piroxicam by administration of activated charcoal or cholestyramine.

    PubMed

    Ferry, D G; Gazeley, L R; Busby, W J; Beasley, D M; Edwards, I R; Campbell, A J

    1990-01-01

    This study has compared the effect of repeated administration of charcoal and cholestyramine on the elimination of piroxicam. Eight young adults were given piroxicam as a single dose of 20 mg, on 3 separate occasions. On one of the occasions charcoal was also given. On another occasion cholestyramine was also administered. The mean elimination half-life after piroxicam alone was 53.1 h. This was reduced to 40.0 h by charcoal administration and to 29.6 h after administration of cholestyramine. In the second phase of the study 7 elderly subjects received piroxicam 20 mg for 14 days on two occasions. Cholestyramine administration at the end of one of the periods reduced the mean elimination half-life of piroxicam from 52.3 h to 27.3 h. PMID:2095346

  8. Early methylphenidate exposure enhances cocaine self-administration but not cocaine-induced conditioned place preference in young adult rats

    PubMed Central

    Crawford, Cynthia A.; Baella, Shelley A.; Farley, Cristal M.; Herbert, Matthew S.; Horn, Leslie R.; Campbell, Rachel H.; Zavala, Arturo R.

    2010-01-01

    Rationale Previous studies in rodents show that early exposure to methylphenidate alters later responsiveness to drugs of abuse. An interesting feature of these studies is that early methylphenidate treatment decreases the rewarding value of cocaine when measured by conditioned place preference (CPP), but the same treatment increases cocaine self-administration. Objective The goal of the present study was to examine the effects of early methylphenidate exposure on cocaine-induced responding using both reward paradigms. Methods Rats were treated with methylphenidate (0, 2, or 5 mg/kg) from postnatal day (PD) 11 to PD 20 and then cocaine-induced CPP or cocaine self-administration was measured in separate groups of rats in adulthood. The CPP procedure included eight days of acquisition training, eight days of extinction training, and a reinstatement test. Rats were conditioned with 0, 10 or 20 mg/kg cocaine. Reinstatement was assessed after a priming dose of cocaine (10 mg/kg). For the self-administration experiment, a jugular catheter was implanted and rats were trained to press a lever reinforced with cocaine (0.25 or 0.75 mg/kg/infusion) on a fixed ratio (FR) 1 schedule. Rats were gradually moved from an FR1 to an FR10 schedule and, after criterion was reached, rats were placed on a progressive ratio schedule for five days. Results Cocaine produced robust rewarding effects as determined by both the CPP and self-administration experiments; however, early methylphenidate exposure only enhanced the reinforcing effects of cocaine on the self-administration paradigm. Interestingly, this methylphenidate enhancement was only seen in male rats. Conclusions These data suggest that in males methylphenidate enhances the reinforcing value of cocaine, but not cocaine-associated cues. PMID:20848087

  9. Difference in method of administration did not significantly impact item response: an IRT-based analysis from the Patient-Reported Outcomes Measurement Information System (PROMIS) initiative

    PubMed Central

    Rose, Matthias; Gandek, Barbara; Stone, Arthur A.; Junghaenel, Doerte U.; Ware, John E.

    2013-01-01

    Purpose To test the impact of method of administration (MOA) on the measurement characteristics of items developed in the Patient-Reported Outcomes Measurement Information System (PROMIS). Methods Two non-overlapping parallel 8-item forms from each of three PROMIS domains (physical function, fatigue, and depression) were completed by 923 adults (age 18–89) with chronic obstructive pulmonary disease, depression, or rheumatoid arthritis. In a randomized crossover design, subjects answered one form by interactive voice response (IVR) technology, paper questionnaire (PQ), personal digital assistant (PDA), or personal computer (PC) on the Internet, and a second form by PC, in the same administration. Structural invariance, equivalence of item responses, and measurement precision were evaluated using confirmatory factor analysis and item response theory methods. Results Multigroup confirmatory factor analysis supported equivalence of factor structure across MOA. Analyses by item response theory found no differences in item location parameters and strongly supported the equivalence of scores across MOA. Conclusions We found no statistically or clinically significant differences in score levels in IVR, PQ, or PDA administration as compared to PC. Availability of large item response theory-calibrated PROMIS item banks allowed for innovations in study design and analysis. PMID:23877585

  10. Enhancing Clinical Content and Race/Ethnicity Data in Statewide Hospital Administrative Databases: Obstacles Encountered, Strategies Adopted, and Lessons Learned

    PubMed Central

    Pine, Michael; Kowlessar, Niranjana M; Salemi, Jason L; Miyamura, Jill; Zingmond, David S; Katz, Nicole E; Schindler, Joe

    2015-01-01

    Objectives Eight grant teams used Agency for Healthcare Research and Quality infrastructure development research grants to enhance the clinical content of and improve race/ethnicity identifiers in statewide all-payer hospital administrative databases. Principal Findings Grantees faced common challenges, including recruiting data partners and ensuring their continued effective participation, acquiring and validating the accuracy and utility of new data elements, and linking data from multiple sources to create internally consistent enhanced administrative databases. Successful strategies to overcome these challenges included aggressively engaging with providers of critical sources of data, emphasizing potential benefits to participants, revising requirements to lessen burdens associated with participation, maintaining continuous communication with participants, being flexible when responding to participants’ difficulties in meeting program requirements, and paying scrupulous attention to preparing data specifications and creating and implementing protocols for data auditing, validation, cleaning, editing, and linking. In addition to common challenges, grantees also had to contend with unique challenges from local environmental factors that shaped the strategies they adopted. Conclusions The creation of enhanced administrative databases to support comparative effectiveness research is difficult, particularly in the face of numerous challenges with recruiting data partners such as competing demands on information technology resources. Excellent communication, flexibility, and attention to detail are essential ingredients in accomplishing this task. Additional research is needed to develop strategies for maintaining these databases when initial funding is exhausted. PMID:26119470

  11. Complete Au@ZnO core-shell nanoparticles with enhanced plasmonic absorption enabling significantly improved photocatalysis.

    PubMed

    Sun, Yiqiang; Sun, Yugang; Zhang, Tao; Chen, Guozhu; Zhang, Fengshou; Liu, Dilong; Cai, Weiping; Li, Yue; Yang, Xianfeng; Li, Cuncheng

    2016-05-19

    Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic absorption in the visible range due to the Au NP cores. They also show a significantly improved photocatalytic performance in comparison with their single-component counterparts, i.e., the Au NPs and ZnO NPs. Moreover, the high catalytic activity of the as-synthesized Au@ZnO core-shell NPs can be maintained even after many cycles of photocatalytic reaction. Our results shed light on the fact that the Au@ZnO core-shell NPs represent a promising class of candidates for applications in plasmonics, surface-enhanced spectroscopy, light harvest devices, solar energy conversion, and degradation of organic pollutants. PMID:27160795

  12. Determination of contrast media administration to achieve a targeted contrast enhancement in CT

    NASA Astrophysics Data System (ADS)

    Sahbaee, Pooyan; Li, Yuan; Segars, Paul; Marin, Daniele; Nelson, Rendon; Samei, Ehsan

    2015-03-01

    Contrast enhancement is a key component of CT imaging and offer opportunities for optimization. The design and optimization of new techniques however requires orchestration with the scan parameters and further a methodology to relate contrast enhancement and injection function. In this study, we used such a methodology to develop a method, analytical inverse method, to predict the required injection function to achieve a desired contrast enhancement in a given organ by incorporation of a physiologically based compartmental model. The method was evaluated across 32 different target contrast enhancement functions for aorta, kidney, stomach, small intestine, and liver. The results exhibited that the analytical inverse method offers accurate performance with error in the range of 10% deviation between the predicted and desired organ enhancement curves. However, this method is incapable of predicting the injection function based on the liver enhancement. The findings of this study can be useful in optimizing contrast medium injection function as well as the scan timing to provide more consistency in the way that the contrast enhanced CT examinations are performed. To our knowledge, this work is one of the first attempts to predict the contrast material injection function for a desired organ enhancement curve.

  13. Significantly enhanced energy output from 3D ordered macroporous structured Fe2O3/Al nanothermite film.

    PubMed

    Zhang, Wenchao; Yin, Baoqing; Shen, Ruiqi; Ye, Jiahai; Thomas, Jason A; Chao, Yimin

    2013-01-23

    A three-dimensionally ordered macroporous Fe(2)O(3)/Al nanothermite membrane has been prepared with a polystyrene spheres template. The nanothermite, with an enhanced interfacial contact between fuel and oxidizer, outputs 2.83 kJ g(-1) of energy. This is significantly more than has been reported before. This approach, fully compatible with MEMS technology, provides an efficient way to produce micrometer thick three-dimensionally ordered nanostructured thermite films with overall spatial uniformity. These exciting achievements will greatly facilitate potential for the future development of applications of nanothermites. PMID:23276147

  14. Mechanical and Electrical Properties of a Polyimide Film Significantly Enhanced by the Addition of Single-Wall Carbon Nanotubes

    NASA Technical Reports Server (NTRS)

    Meador, Michael A.

    2005-01-01

    Single-wall carbon nanotubes have been shown to possess a combination of outstanding mechanical, electrical, and thermal properties. The use of carbon nanotubes as an additive to improve the mechanical properties of polymers and/or enhance their thermal and electrical conductivity has been a topic of intense interest. Nanotube-modified polymeric materials could find a variety of applications in NASA missions including large-area antennas, solar arrays, and solar sails; radiation shielding materials for vehicles, habitats, and extravehicular activity suits; and multifunctional materials for vehicle structures and habitats. Use of these revolutionary materials could reduce vehicle weight significantly and improve vehicle performance and capabilities.

  15. Comparing the diagnostic accuracy of contrast-enhanced computed tomographic angiography and gadolinium-enhanced magnetic resonance angiography for the assessment of hemodynamically significant transplant renal artery stenosis.

    PubMed

    Gaddikeri, Santhosh; Mitsumori, Lee; Vaidya, Sandeep; Hippe, Daniel S; Bhargava, Puneet; Dighe, Manjiri K

    2014-01-01

    To compare diagnostic accuracy of contrast-enhanced computed tomographic angiography (CTA) and gadolinium-enhanced magnetic resonance angiography (MRA) for the assessment of hemodynamically significant transplant renal artery stenosis (TRAS). After institutional review board approval, records of 27 patients with TRAS confirmed on digital subtraction angiography (DSA) were retrospectively reviewed. A total of 13 patients had MRA and 14 had CTA before DSA. Two board-certified fellowship-trained radiologists, one each from interventional radiology and body imaging blindly reviewed the DSA and CTA or MRA data, respectively. Sensitivity (SN), specificity (SP), positive predictive value, and negative predictive value of MRA and CTA were estimated using 50% stenosis as the detection threshold for significant TRAS. These parameters were compared between modalities using the Fisher exact test. Bias between MRA or CTA imaging and DSA was tested using the Wilcoxon signed-rank test. Two patients were excluded from the MRA group owing to susceptibility artifacts obscuring the TRAS. The correlation between MRA and DSA measurements of stenosis was r = 0.57 (95% CI:-0.02, 0.87; P = 0.052) and between CTA and DSA measurements was r = 0.63 (95% CI: 0.14, 0.87; P = 0.015); the difference between the 2 techniques was not significant (P = 0.7). Both imaging modalities tended to underestimate the degree of stenosis when compared with DSA. MRA group (SN and SP: 56% and 100%, respectively) and CTA group (SN and SP: 81% and 67%, respectively). There were no significant differences in detection performance between modalities (P>0.3 for all measures). We did not find that either modality had any advantage over the other in terms of measuring or detecting significant stenosis. Accordingly, MRA may be preferred over CTA after positive color Doppler ultrasound screening when not contraindicated owing to lack of ionizing radiation or nephrotoxic iodinated contrast. However, susceptibility of

  16. Zero Valent Iron Significantly Enhances Methane Production from Waste Activated Sludge by Improving Biochemical Methane Potential Rather Than Hydrolysis Rate

    PubMed Central

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-01-01

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system. PMID:25652244

  17. Zero Valent Iron Significantly Enhances Methane Production from Waste Activated Sludge by Improving Biochemical Methane Potential Rather Than Hydrolysis Rate

    NASA Astrophysics Data System (ADS)

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-02-01

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

  18. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    PubMed Central

    Liu, Yiwen; Ni, Bing-Jie

    2015-01-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d−1 compared to 0.118 d−1 at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment. PMID:25644239

  19. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    NASA Astrophysics Data System (ADS)

    Liu, Yiwen; Ni, Bing-Jie

    2015-02-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d-1 compared to 0.118 d-1 at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment.

  20. Evaluating clinically significant change in mother and child functioning: comparison of traditional and enhanced behavioral parent training.

    PubMed

    Rajwan, Estrella; Chacko, Anil; Wymbs, Brian T; Wymbs, Frances A

    2014-11-01

    The Strategies to Enhance Positive Parenting (STEPP) program, an enhanced behavioral parent training (BPT) intervention, was developed to improve engagement in and outcomes following treatment for single-mother families of school-age youth with attention-deficit/hyperactivity disorder (ADHD). A previous randomized clinical trial of the STEPP program demonstrated that the intervention resulted in statistically significant improvements at the group-level in child oppositional behavior, various areas of child impairment, parental stress, and parenting behavior, relative to a wait-list control condition and a traditional BPT group. Despite benefits at the group-level, little is known about outcomes at the individual-level of enhanced BPT relative to traditional BPT for various child- and parent-level outcomes. The current study compares the extent to which traditional BPT and the STEPP program result in reliable change and recovery across various child- and parent-level outcomes in a sample of 80, 5-12 year old youth with ADHD (70 % male). Analyses demonstrated the benefit of participating in either BPT treatment; and participation in the STEPP program compared to traditional BPT was associated with only minimal incremental clinical benefit. Results, as well as clinical and research implications for assessment and treatment of high-risk families of youth with ADHD enrolled in BPT are discussed. PMID:24740438

  1. Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

    PubMed

    Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

    2016-05-01

    Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. PMID:26897537

  2. The effect of glucose administration on the emotional enhancement effect in recognition memory.

    PubMed

    Brandt, Karen R; Sünram-Lea, Sandra I; Qualtrough, Kirsty

    2006-08-01

    Previous research has demonstrated that glucose administration improves memory performance. However few studies have addressed the effects of glucose on emotional material that by nature already enjoys a memory advantage. The aim of the present research was therefore to investigate whether the memory facilitation effect associated with glucose would emerge for emotional words. Experiment 1 demonstrated that negative words were better recognized and remembered than positive and neutral words. Experiment 2 further explored these effects under conditions of glucose administration and an aspartame control. The results revealed that both the aspartame and glucose groups replicated the results from Experiment 1. The present research therefore demonstrated that the glucose facilitation effect did not emerge for material that already benefits from a memory advantage. These results also raise the question of whether the dose response relationship previously associated with glucose administration is applicable when the information being processed is of an emotional nature. PMID:16713059

  3. Significant Other Enhanced Cognitive-Behavioral Therapy for PTSD and Alcohol Misuse in OEF/OIF Veterans

    PubMed Central

    McDevitt-Murphy, Meghan E.

    2012-01-01

    This manuscript describes early work to develop a cognitive-behavioral therapy protocol for returning OEF/OIF Veterans with co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD). Based on the unique characteristics of this population, and on the literature supporting cognitive behavioral coping skills and significant other involvement for both PTSD and for AUD, the new therapy involves both of those components. The paper includes brief descriptions of two patients who were successfully treated with this approach. Although preliminary, these case studies suggest that cognitive-behavioral therapy enhanced by significant other involvement may be a promising approach for OEF/OIF Veterans with PTSD-AUD. PMID:23750071

  4. Significantly enhanced high-frequency permeability for composites with amorphous-membrane-fillers prepared using an infiltration method

    NASA Astrophysics Data System (ADS)

    Li, Z. W.; Yang, Z. H.

    2016-03-01

    Amorphous-membrane-filler composites have been fabricated using an infiltration method. The composites are able to significantly increase the permeability by 200%, as compared to general amorphous flake composites. SEM and magnetic measurement show that the amorphous flakes in membrane are in-plane arrangement. A model, which considers the effect of flake arrangement on demagnetizing factor Nd and permeability, is proposed. The effect of the arrangement of flakes is equivalent to an effective Nd, which is equal to 1/3 and zero for random and complete in-plane arrangements, respectively. Due to in-plane arrangement of amorphous flakes, the decreased Nd leads to significantly enhanced permeability for the amorphous-membrane-filler composites, based on the Maxwell-Garret mixing law.

  5. National Dissemination of Motivation Enhancement Therapy in the Veterans Health Administration: Training Program Design and Initial Outcomes.

    PubMed

    Drapkin, Michelle L; Wilbourne, Paula; Manuel, Jennifer K; Baer, John; Karlin, Bradley; Raffa, Susan

    2016-06-01

    Motivational enhancement therapy (MET) can be defined most simply as the "….combination of Motivational Interviewing (MI) with assessment feedback…." (Miller & Rollnick, 2013, p. 250). MET has a clear evidence-base promoting its use especially for treatment of substance use disorders (SUDs). Despite its efficacy and utility, MET is not widely used in clinical settings. In 2012, to facilitate the dissemination of MET, the Veterans Health Administration [VHA; the health care component of the U.S. Department of Veterans Affairs (VA)] launched a national training program that provided competency-based training in MET to VA staff working in SUD specialty care clinics. All VA facilities are required to implement EBPs for SUDs, such as MET, and ensure that they are available to veterans. This paper describes the VA MET training program and examines the impact of the MET training program on participants' knowledge of MET and self-reported MET skills. We review the components of the training and consultation and discuss adaptations made from the Project MATCH MET model to a real-world clinical setting. Of the 264 training participants we trained 2012-2013, 213 (81%) successfully completed all requirements of the training program, including requirements for demonstrating competency and attending at least 75% of scheduled consultation calls. After completion of the training program, approximately 85% of the clinicians reported implementing MET often (either 1-3 times per week or daily). Furthermore, we saw significant increases in MI knowledge from pretraining assessment to post-workshop and from pretraining to post-consultations. Additional training program details and revisions are discussed. PMID:26951921

  6. Using CD-ROM to Provide Enhanced Information Services for University Administrators and Committees.

    ERIC Educational Resources Information Center

    Ensor, Pat; Hardin, Steve

    1991-01-01

    Discusses information needs of university administrators and committees, and describes the development of an information service provided by the Electronic Information Services (EIS) unit of the Indiana State University library. Highlights include staff reactions, a pilot test, marketing the service, cost effectiveness of CD-ROM use, and document…

  7. Cinnamon Administration Enhances Glucose-Induced Insulin Secretion in Diabetic Rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of these studies was to measure the effects of orally administered cinnamon on glucose tolerance and insulin secretion in vivo. Young male Wistar strain rats were rendered diabetic by intravenous administration of streptozotocin (40 mg/Kg body weight) to produce animals with Type 2 di...

  8. Significance of Additional Non-Mass Enhancement in Patients with Breast Cancer on Preoperative 3T Dynamic Contrast Enhanced MRI of the Breast

    PubMed Central

    Cho, Yun Hee; Cho, Kyu Ran; Park, Eun Kyung; Seo, Bo Kyoung; Woo, Ok Hee; Cho, Sung Bum; Bae, Jeoung Won

    2016-01-01

    Background In preoperative assessment of breast cancer, MRI has been shown to identify more additional breast lesions than are detectable using conventional imaging techniques. The characterization of additional lesions is more important than detection for optimal surgical treatment. Additional breast lesions can be included in focus, mass, and non-mass enhancement (NME) on MRI. According to the fifth edition of the breast imaging reporting and data system (BI-RADS®), which includes several changes in the NME descriptors, few studies to date have evaluated NME in preoperative assessment of breast cancer. Objectives We investigated the diagnostic accuracy of BI-RADS descriptors in predicting malignancy for additional NME lesions detected on preoperative 3T dynamic contrast enhanced MRI (DCE-MRI) in patients with newly diagnosed breast cancer. Patients and Methods Between January 2008 and December 2012, 88 patients were enrolled in our study, all with NME lesions other than the index cancer on preoperative 3T DCE-MRI and all with accompanying histopathologic examination. The MRI findings were analyzed according to the BI-RADS MRI lexicon. We evaluated the size, distribution, internal enhancement pattern, and location of NME lesions relative to the index cancer (i.e., same quadrant, different quadrant, or contralateral breast). Results On histopathologic analysis of the 88 NME lesions, 73 (83%) were malignant and 15 (17%) were benign. Lesion size did not differ significantly between malignant and benign lesions (P = 0.410). Malignancy was more frequent in linear (P = 0.005) and segmental (P = 0.011) distributions, and benignancy was more frequent in focal (P = 0.004) and regional (P < 0.001) NME lesions. The highest positive predictive value (PPV) for malignancy occurred in segmental (96.8%), linear (95.1%), clustered ring (100%), and clumped (92.0%) enhancement. Asymmetry demonstrated a high positive predictive value of 85.9%. The frequency of malignancy was higher

  9. Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma.

    PubMed

    Hillengass, Jens; Ritsch, Judith; Merz, Maximilian; Wagner, Barbara; Kunz, Christina; Hielscher, Thomas; Laue, Hendrik; Bäuerle, Tobias; Zechmann, Christian M; Ho, Anthony D; Schlemmer, Heinz-Peter; Goldschmidt, Hartmut; Moehler, Thomas M; Delorme, Stefan

    2016-07-01

    This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0·89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS. PMID:26991959

  10. Complete Au@ZnO core-shell nanoparticles with enhanced plasmonic absorption enabling significantly improved photocatalysis

    NASA Astrophysics Data System (ADS)

    Sun, Yiqiang; Sun, Yugang; Zhang, Tao; Chen, Guozhu; Zhang, Fengshou; Liu, Dilong; Cai, Weiping; Li, Yue; Yang, Xianfeng; Li, Cuncheng

    2016-05-01

    Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic absorption in the visible range due to the Au NP cores. They also show a significantly improved photocatalytic performance in comparison with their single-component counterparts, i.e., the Au NPs and ZnO NPs. Moreover, the high catalytic activity of the as-synthesized Au@ZnO core-shell NPs can be maintained even after many cycles of photocatalytic reaction. Our results shed light on the fact that the Au@ZnO core-shell NPs represent a promising class of candidates for applications in plasmonics, surface-enhanced spectroscopy, light harvest devices, solar energy conversion, and degradation of organic pollutants.Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic

  11. Bacteriophage administration significantly reduces Shigella colonization and shedding by Shigella-challenged mice without deleterious side effects and distortions in the gut microbiota

    PubMed Central

    Mai, Volker; Ukhanova, Maria; Reinhard, Mary K; Li, Manrong; Sulakvelidze, Alexander

    2015-01-01

    We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecal Shigella counts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged with Shigella sonnei strain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lytic Shigella bacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActiveTM treatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration. Shigella phages may be therapeutically effective in a “classical phage therapy” approach, at least during the early stages after Shigella ingestion. Oral prophylactic “phagebiotic” administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota. PMID:26909243

  12. Post-training and post-reactivation administration of amphetamine enhances morphine conditioned place preference

    PubMed Central

    Blaiss, Cory A.; Janak, Patricia H.

    2006-01-01

    Amphetamine has been shown to enhance consolidation in a variety of memory paradigms. However, it is not known if amphetamine can modulate the consolidation of the types of context-reward associations involved in drug addiction, such as those formed in the conditioned place preference (CPP) task. Also, some types of memory exhibit a second period of lability following memory reactivation, and it is not known whether amphetamine administered during this period can modulate CPP. Our study investigated whether amphetamine can enhance morphine CPP when administered during the consolidation period or the post-reactivation period. Subjects were trained in the CPP task and injected with amphetamine or vehicle immediately or six hours after each training session. The day after the completion of training, they were tested. Amphetamine injected immediately but not six hours after training enhanced morphine CPP. In separate experiments, subjects were first trained in the CPP task. The day following the completion of training, subjects were given a memory reactivation session and injected with amphetamine or vehicle immediately or six hours after reactivation. Subjects were tested the next day. Amphetamine injected immediately but not six hours after memory reactivation enhanced morphine CPP. However, amphetamine injected without memory reactivation had no effect on the expression of morphine CPP. Our results suggest that amphetamine enhances the consolidation of morphine CPP and that morphine CPP exhibits a temporally limited period of post-reactivation lability during which the memory can be modulated. PMID:16698095

  13. The use of logistic regression to enhance risk assessment and decision making by mental health administrators.

    PubMed

    Menditto, Anthony A; Linhorst, Donald M; Coleman, James C; Beck, Niels C

    2006-04-01

    Development of policies and procedures to contend with the risks presented by elopement, aggression, and suicidal behaviors are long-standing challenges for mental health administrators. Guidance in making such judgments can be obtained through the use of a multivariate statistical technique known as logistic regression. This procedure can be used to develop a predictive equation that is mathematically formulated to use the best combination of predictors, rather than considering just one factor at a time. This paper presents an overview of logistic regression and its utility in mental health administrative decision making. A case example of its application is presented using data on elopements from Missouri's long-term state psychiatric hospitals. Ultimately, the use of statistical prediction analyses tempered with differential qualitative weighting of classification errors can augment decision-making processes in a manner that provides guidance and flexibility while wrestling with the complex problem of risk assessment and decision making. PMID:16645908

  14. Varenicline impairs extinction and enhances reinstatement across repeated cycles of nicotine self-administration in rats.

    PubMed

    Macnamara, Claire L; Holmes, Nathan M; Westbrook, R Fred; Clemens, Kelly J

    2016-06-01

    Varenicline is a partial nicotine receptor agonist widely prescribed as a smoking cessation medication. Repeated (or long-term) use of varenicline has been proposed as a treatment option for tobacco addiction. However the effect of repeated varenicline use on motivation for nicotine is unknown. Here the intravenous nicotine self-administration paradigm in rats was used to model the consequences of varenicline treatment across repeated cycles of administration, extinction and reinstatement. Rats acquired nicotine self-administration across 20 days before undergoing 6 days of extinction, where each extinction session was preceded by a single injection of varenicline or saline. This was followed by a single varenicline-free nicotine-primed reinstatement test. All rats then reacquired nicotine self-administration for 10 days followed by a second cycle of extinction. Across this period, rats either received a second cycle of varenicline (VAR-VAR) or saline (SAL-SAL), or the alternative treatment (SAL-VAR, VAR-SAL), followed by a final reinstatement test. Treatment with varenicline increased responding across the first cycle of extinction, but did not affect responding in the reinstatement test. Across the second cycle, varenicline again increased responding across extinction, and critically, rats treated with varenicline across cycle 1 and saline across cycle 2 (Group VAR-SAL) exhibited more reinstatement than rats in any other group. The effect of VAR on nicotine seeking was not due to its effects on locomotor activity. Instead, the results suggest that a history of VAR can increase vulnerability to reinstatement/relapse when its treatment is discontinued. The possible mechanisms of this increased vulnerability are discussed. PMID:26907808

  15. Postoperative irradiation impairs or enhances wound strength depending on time of administration

    SciTech Connect

    Vegesna, V.; McBride, W.H.; Withers, H.R.

    1995-08-01

    Irradiation can complicate surgical wound healing, yet little is known of the importance of the time between surgery and irradiation on this process. This study investigated the impact of post-operative irradiation on gain in wound tensile strength in a murine skin model. Irradiation on the same day as wounding or to 2-day-old wounds reduced wound tensile strength. In contrast, postoperative irradiation delivered at 7, 9 and 14 days transiently enhanced wound tensile strength, as measure d 3 but not 4 or 5 weeks later. This effect was independent of the inclusion (hemi-body) or exclusion (skin alone) of the hematopoietic system in the field of irradiation. Radiation-enhanced wound tensile strength was greater and occurred earlier after higher radiation doses. Even though the effect of irradiation in enhancing wound tensile strength is transitory, it could be important in assisting early wound healing. 14 refs., 3 figs., 1 tab.

  16. Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

    PubMed Central

    Ma, Yufan; Lu, Tingli; Zhao, Wen; Wang, Ying; Chen, Ting; Mei, Qibing

    2014-01-01

    Artemether and lumefantrine (also known as benflumetol) are difficult to formulate for parenteral administration because of their low aqueous solubility. Cremophor EL as an emulsion excipient has been shown to cause serious side effects. This study reports a method of preparation and the therapeutic efficacies of novel lipid emulsion (LE) delivery systems with artemether, lumefantrine, or artemether in combination with lumefantrine, for parenteral administration. Their physical and chemical stabilities were also evaluated. Furthermore, the in vivo antimalarial activities of the lipid emulsions developed were tested in Plasmodium berghei-infected mice. Artemether, lumefantrine, or artemether in combination with lumefantrine was encapsulated in an oil phase, and the in vivo performance was assessed by comparison with artesunate for injection. It was found that the lumefantrine lipid emulsion (LUM-LE) and artemether-lumefantrine lipid emulsion (ARM-LUM-LE-3) (1:6) began to decrease the parasitemia levels after only 3 days, and the parasitemia inhibition was 90% at doses of 0.32 and 0.27 mg/kg, respectively, with immediate antimalarial effects greater than those of the positive-control group and constant antimalarial effects over 30 days. LUM-LE and ARM-LUM-LE-3 demonstrated the best performance in terms of chemical and physical stabilities and antiplasmodial efficacy, with a mean particle size of 150 nm, and they have many favorable properties for parenteral administration, such as biocompatibility, physical stability, and ease of preparation. PMID:24982079

  17. Implementation of the Enhanced Flight Termination System at National Aeronautics and Space Administration Dryden Flight Research Center

    NASA Technical Reports Server (NTRS)

    Tow, David

    2010-01-01

    This paper discusses the methodology, requirements, tests, and results of the implementation of the current operating capability for the Enhanced Flight Termination System (EFTS) at the National Aeronautics and Space Administration (NASA) Dryden Flight Research Center (DFRC). The implementation involves the development of the EFTS at NASA DFRC starting from the requirements to system safety review to full end to end system testing, and concluding with the acceptance of the system as an operational system. The paper discusses the first operational usage and subsequent flight utilizing EFTS successfully.

  18. Adenovirus-Mediated Gene Transfer in Mesenchymal Stem Cells Can Be Significantly Enhanced by the Cationic Polymer Polybrene

    PubMed Central

    Zhao, Chen; Wu, Ningning; Deng, Fang; Zhang, Hongmei; Wang, Ning; Zhang, Wenwen; Chen, Xian; Wen, Sheng; Zhang, Junhui; Yin, Liangjun; Liao, Zhan; Zhang, Zhonglin; Zhang, Qian; Yan, Zhengjian; Liu, Wei; Wu, Di; Ye, Jixing; Deng, Youlin; Zhou, Guolin; Luu, Hue H.; Haydon, Rex C.; Si, Weike; He, Tong-Chuan

    2014-01-01

    Mesenchymal stem cells (MSCs) are multipotent progenitors, which can undergo self-renewal and give rise to multi-lineages. A great deal of attentions have been paid to their potential use in regenerative medicine as potential therapeutic genes can be introduced into MSCs. Genetic manipulations in MSCs requires effective gene deliveries. Recombinant adenoviruses are widely used gene transfer vectors. We have found that although MSCs can be infected in vitro by adenoviruses, high virus titers are needed to achieve high efficiency. Here, we investigate if the commonly-used cationic polymer Polybrene can potentiate adenovirus-mediated transgene delivery into MSCs, such as C2C12 cells and iMEFs. Using the AdRFP adenovirus, we find that AdRFP transduction efficiency is significantly increased by Polybrene in a dose-dependent fashion peaking at 8 μg/ml in C2C12 and iMEFs cells. Quantitative luciferase assay reveals that Polybrene significantly enhances AdFLuc-mediated luciferase activity in C2C12 and iMEFs at as low as 4 μg/ml and 2 μg/ml, respectively. FACS analysis indicates that Polybrene (at 4 μg/ml) increases the percentage of RFP-positive cells by approximately 430 folds in AdRFP-transduced iMEFs, suggesting Polybrene may increase adenovirus infection efficiency. Furthermore, Polybrene can enhance AdBMP9-induced osteogenic differentiation of MSCs as early osteogenic marker alkaline phosphatase activity can be increased more than 73 folds by Polybrene (4 μg/ml) in AdBMP9-transduced iMEFs. No cytotoxicity was observed in C2C12 and iMEFs at Polybrene up to 40 μg/ml, which is about 10-fold higher than the effective concentration required to enhance adenovirus transduction in MSCs. Taken together, our results demonstrate that Polybrene should be routinely used as a safe, effective and inexpensive augmenting agent for adenovirus-mediated gene transfer in MSCs, as well as other types of mammalian cells. PMID:24658746

  19. Short-term repeated corticosterone administration enhances glutamatergic but not GABAergic transmission in the rat motor cortex.

    PubMed

    Kula, Joanna; Blasiak, Anna; Czerw, Anna; Tylko, Grzegorz; Sowa, Joanna; Hess, Grzegorz

    2016-04-01

    It has been demonstrated that stress impairs performance of skilled reaching and walking tasks in rats due to the action of glucocorticoids involved in the stress response. Skilled reaching and walking are controlled by the primary motor cortex (M1); however, it is not known whether stress-related impairments in skilled motor tasks are related to functional and/or structural alterations within the M1. We studied the effects of single and repeated injections of corticosterone (twice daily for 7 days) on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) recorded from layer II/III pyramidal neurons in ex vivo slices of the M1, prepared 2 days after the last administration of the hormone. We also measured the density of dendritic spines on pyramidal cells and the protein levels of selected subunits of AMPA, NMDA, and GABAA receptors after repeated corticosterone administration. Repeatedly administered corticosterone induced an increase in the frequency but not in the amplitude of sEPSCs, while a single administration had no effect on the recorded excitatory currents. The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells were changed neither after single nor after repeated corticosterone administration. Treatment with corticosterone for 7 days did not modify the density of dendritic spines on pyramidal neurons. Corticosterone influenced neither the protein levels of GluA1, GluA2, GluN1, GluN2A, and GluN2B subunits of glutamate receptors nor those of α1, β2, and γ2 subunits of the GABAA receptor. The increase in sEPSCs frequency induced by repeated corticosterone administration faded out within 7 days. These data indicate that prolonged administration of exogenous corticosterone selectively and reversibly enhances glutamatergic, but not GABAergic transmission in the rat motor cortex. Our results suggest that corticosterone treatment results in an enhancement of spontaneous glutamate release from

  20. Enhanced Absorption of Nasulin™, an Ultrarapid-Acting Intranasal Insulin Formulation, Using Single Nostril Administration in Normal Subjects

    PubMed Central

    Stote, Robert; Miller, Michael; Marbury, Thomas; Shi, Leon; Strange, Poul

    2011-01-01

    Background This pharmacokinetic (PK) study was designed to investigate the maximum intranasal insulin dose that could be achieved by repeated doses in a single nostril of a nasal spray of recombinant regular human insulin 1% in combination with cyclopentadecalactone (CPE-215) 2%, a compound that enhances absorption of molecules across mucous membranes (Nasulin™, CPEX Pharmaceuticals, Inc.). Method A nine-period crossover study of 8 healthy, nonsmoking subjects (ages 18–50, body mass index <33 kg/m2, weight >70 kg) were studied. In a fasted state, subjects were randomly given 25, 50, and 75 U in a single nostril on the first day and randomly given 50, 75, and 100 U doses utilizing both nostrils on two subsequent days. After a 45-minute PK assessment, subjects were given a meal. To determine the mechanism of enhanced absorption in a single nostril, a second study utilizing 24 subjects under similar conditions received 25 U, placebo (P) that included CPE-215 plus 25 U, and 50 U in a single nostril. Results Single nostril administration revealed enhanced absorption with maximum concentrations (Cmax) of 13, 65, and 96 µU/ml for the 25, 50, and 75 U doses, respectively. Dual nostril administration in two cohorts resulted in Cmax of 31/42, 65/52, and 88/79 µU/ml for the 50, 75, and 100 U, respectively. In the second cohort, Cmax was 23, 19, 56 µU/ml for the 25, P + 25, and 50 U doses, respectively. Conclusions Repeated dosing in a single nostril resulted in enhanced absorption; this was not due to the increased CPE-215 but to the increased insulin administered. PMID:21303633

  1. Enhancement of the curative activity of primaquine by concomitant administration of mirincamycin.

    PubMed

    Schmidt, L H

    1985-02-01

    Mirincamycin, a lincomycin derivative with unequivocal but limited activity against the pre-erythrocytic and persisting exoerythrocytic stages of Plasmodium cynomolgi, has been evaluated for capacity to enhance the radical curative potential of the conventional primaquine-chloroquine combination. Established infections with sporozoites of the above plasmodium in rhesus monkeys served this evaluation. The results showed that the dose of primaquine required for cure of 50% of active infections was reduced by one-half to two-thirds by coadministration with 2.5 mg of mirincamycin per kg, 1/16 the 50% curative dose of this lincomycin derivative when used in a mono-drug regimen. The dimensions of the enhancement of the curative activity of primaquine were inversely related to the size of the sporozoite inoculum. The smallest dose of mirincamycin productive of enhancement was 2.5 mg/kg; whether doses larger than 2.5 mg/kg would have been more effective was not determined. There is much to be done before it is known whether a mirincamycin-primaquine combination is useful for suppressive cure or radical cure of the human malarias. Irrespective of that result, the current study serves to focus attention on a somewhat novel approach to the development of more effective and better-tolerated regimens for radical cure, an alternative to the empirical chemical synthesis and screening approach that has dominated searches heretofore. PMID:3885847

  2. Enhancement of the curative activity of primaquine by concomitant administration of mirincamycin.

    PubMed Central

    Schmidt, L H

    1985-01-01

    Mirincamycin, a lincomycin derivative with unequivocal but limited activity against the pre-erythrocytic and persisting exoerythrocytic stages of Plasmodium cynomolgi, has been evaluated for capacity to enhance the radical curative potential of the conventional primaquine-chloroquine combination. Established infections with sporozoites of the above plasmodium in rhesus monkeys served this evaluation. The results showed that the dose of primaquine required for cure of 50% of active infections was reduced by one-half to two-thirds by coadministration with 2.5 mg of mirincamycin per kg, 1/16 the 50% curative dose of this lincomycin derivative when used in a mono-drug regimen. The dimensions of the enhancement of the curative activity of primaquine were inversely related to the size of the sporozoite inoculum. The smallest dose of mirincamycin productive of enhancement was 2.5 mg/kg; whether doses larger than 2.5 mg/kg would have been more effective was not determined. There is much to be done before it is known whether a mirincamycin-primaquine combination is useful for suppressive cure or radical cure of the human malarias. Irrespective of that result, the current study serves to focus attention on a somewhat novel approach to the development of more effective and better-tolerated regimens for radical cure, an alternative to the empirical chemical synthesis and screening approach that has dominated searches heretofore. PMID:3885847

  3. The combination of immunosuppression and carrier cells significantly enhances the efficacy of oncolytic poxvirus in the pre-immunized host.

    PubMed

    Guo, Z S; Parimi, V; O'Malley, M E; Thirunavukarasu, P; Sathaiah, M; Austin, F; Bartlett, D L

    2010-12-01

    Pre-existing antipoxvirus immunity in cancer patients presents a severe barrier to poxvirus-mediated oncolytic virotherapy. We have explored strategies of immunosuppression (IS) and/or immune evasion for efficient delivery of an oncolytic double-deleted vaccinia virus (vvDD) to tumors in the pre-immunized mice. Transient IS using immunosuppressive drugs, including tacrolimus, mycophenolate mofetil and methylprednisolone sodium succinate, have been used successfully in organ transplantation. This drug cocktail alone did not enhance viral recovery from subcutaneous tumor after systemic viral delivery. Using B-cell knockout mice, we confirmed that the neutralizing antibodies had a significant role in preventing poxvirus infection. Using a MC38 peritoneal carcinomatosis model, we found that the combination of IS and tumor cells as carriers led to the most effective viral delivery, viral replication and viral spread inside the tumor mass. We found that our immunosuppressive drug cocktail facilitated recruitment of tumor-associated macrophages and conversion into an immunosuppressive M2 phenotype (interleukin (IL)-10(hi)/IL-12(low)) in the tumor microenvironment. A combination of IS and carrier cells led to significantly prolonged survival in the tumor model. These results showed the feasibility of treating pre-vaccinated patients with peritoneal carcinomatosis using an oncolytic poxvirus and a combined immune intervention strategy. PMID:20703311

  4. Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

    PubMed

    Wilding, Laura A; Bassis, Christine M; Walacavage, Kim; Hashway, Sara; Leroueil, Pascale R; Morishita, Masako; Maynard, Andrew D; Philbert, Martin A; Bergin, Ingrid L

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome. PMID:26525505

  5. Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

    PubMed

    Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Tabassum, Saiqa; Madiha, Syeda; Rafiq, Sahar; Tariq, Sumayya; Batool, Tuba Sharf; Saleem, Sadia; Naqvi, Fizza; Perveen, Tahira; Haider, Saida

    2016-01-01

    Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond. PMID:26548495

  6. Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin.

    PubMed

    Wei, Qiang; Liu, Li; Cong, Zhe; Wu, Xiaoxian; Wang, Hui; Qin, Chuan; Molina, Patricia; Chen, Zhiwei

    2016-09-01

    Delta9-tetrahydrocannabinol (Δ(9)-THC) is the major psychoactive component of the cannabis plant. Δ(9)-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ(9)-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Here, we determine the chronic effect of Δ(9)-THC administration using 0.32 mg/kg or placebo (PBO), i.m., twice daily for 428 days on SIVmac251 infected male Chinese-derived rhesus macaques. Sixteen animals were divided into four study groups: Δ(9)-THC(+)SIV(+), Δ(9)-THC(+)SIV(-), PBO/SIV(+) and PBO/SIV(-) (n = 4/group). One-month after daily Δ(9)-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIVmac251/CNS, which was isolated from the brain of a Chinese macaque with end-staged neuroAIDS. No significant differences in peak and steady state plasma viral loads were seen between Δ(9)-THC(+)SIV(+) and PBO/SIV(+) macaques. Regardless of Δ(9)-THC, all infected macaques displayed significant drop of CD4/CD8 T cell ratio, loss of CD4(+) T cells and higher persistent levels of Ki67(+)CD8(+) T cells compared with uninfected animals. Moreover, long-term Δ(9)-THC treatment reduced significantly the frequency of circulating IgE(+)B cells. Only one Δ(9)-THC(+)SIV(+) macaque died of simian AIDS with paralyzed limbs compared with two deaths in the PBO/SIV(+) group during the study period. These findings indicate that chronic Δ(9)-THC administration resulted in reduction of IgE(+)B cells, yet it unlikely enhanced pathogenic SIVmac251/CNS infection in male Rhesus macaques of Chinese origin. PMID:27109234

  7. Ozone-Induced Dissociation of Conjugated Lipids Reveals Significant Reaction Rate Enhancements and Characteristic Odd-Electron Product Ions

    NASA Astrophysics Data System (ADS)

    Pham, Huong T.; Maccarone, Alan T.; Campbell, J. Larry; Mitchell, Todd W.; Blanksby, Stephen J.

    2013-02-01

    Ozone-induced dissociation (OzID) is an alternative ion activation method that relies on the gas phase ion-molecule reaction between a mass-selected target ion and ozone in an ion trap mass spectrometer. Herein, we evaluated the performance of OzID for both the structural elucidation and selective detection of conjugated carbon-carbon double bond motifs within lipids. The relative reactivity trends for [M + X]+ ions (where X = Li, Na, K) formed via electrospray ionization (ESI) of conjugated versus nonconjugated fatty acid methyl esters (FAMEs) were examined using two different OzID-enabled linear ion-trap mass spectrometers. Compared with nonconjugated analogues, FAMEs derived from conjugated linoleic acids were found to react up to 200 times faster and to yield characteristic radical cations. The significantly enhanced reactivity of conjugated isomers means that OzID product ions can be observed without invoking a reaction delay in the experimental sequence (i.e., trapping of ions in the presence of ozone is not required). This possibility has been exploited to undertake neutral-loss scans on a triple quadrupole mass spectrometer targeting characteristic OzID transitions. Such analyses reveal the presence of conjugated double bonds in lipids extracted from selected foodstuffs. Finally, by benchmarking of the absolute ozone concentration inside the ion trap, second order rate constants for the gas phase reactions between unsaturated organic ions and ozone were obtained. These results demonstrate a significant influence of the adducting metal on reaction rate constants in the fashion Li > Na > K.

  8. Significance of Late Gadolinium Enhancement at Right Ventricular Attachment to Ventricular Septum in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Chan, Raymond H; Maron, Barry J; Olivotto, Iacopo; Assenza, Gabriele E; Haas, Tammy S; Lesser, John R; Gruner, Christiane; Crean, Andrew M; Rakowski, Harry; Rowin, Ethan; Udelson, James; Lombardi, Massimo; Tomberli, Benedetta; Spirito, Paolo; Formisano, Francesco; Marra, Martina P; Biagini, Elena; Autore, Camillo; Manning, Warren J; Appelbaum, Evan; Roberts, William C; Basso, Cristina; Maron, Martin S

    2015-08-01

    Cardiovascular magnetic resonance (CMR) with extensive late gadolinium enhancement (LGE) is a novel marker for increased risk for sudden death (SD) in patients with hypertrophic cardiomyopathy (HC). Small focal areas of LGE confined to the region of right ventricular (RV) insertion to ventricular septum (VS) have emerged as a frequent and highly visible CMR imaging pattern of uncertain significance. The aim of this study was to evaluate the prognostic significance of LGE confined to the RV insertion area in patients with HC. CMR was performed in 1,293 consecutive patients with HC from 7 HC centers, followed for 3.4 ± 1.7 years. Of 1,293 patients (47 ± 14 years), 134 (10%) had LGE present only in the anterior and/or inferior areas of the RV insertion to VS, occupying 3.7 ± 2.9% of left ventricular myocardium. Neither the presence nor extent of LGE in these isolated areas was a predictor of adverse HC-related risk, including SD (adjusted hazard ratio 0.82, 95% confidence interval 0.45 to 1.50, p = 0.53; adjusted hazard ratio 1.16/10% increase in LGE, 95% confidence interval 0.29 to 4.65, p = 0.83, respectively). Histopathology in 20 HC hearts show the insertion areas of RV attachment to be composed of a greatly expanded extracellular space characterized predominantly by interstitial-type fibrosis and interspersed disorganized myocyte patterns and architecture. In conclusion, LGE confined to the insertion areas of RV to VS was associated with low risk of adverse events (including SD). Gadolinium pooling in this region of the left ventricle does not reflect myocyte death and repair with replacement fibrosis or scarring. PMID:26026863

  9. "Fungal elicitors combined with a sucrose feed significantly enhance triterpene production of a Salvia fruticosa cell suspension".

    PubMed

    Kümmritz, Sibylle; Louis, Marilena; Haas, Christiane; Oehmichen, Franz; Gantz, Stephanie; Delenk, Hubertus; Steudler, Susanne; Bley, Thomas; Steingroewer, Juliane

    2016-08-01

    Oleanolic (OA) and ursolic acid (UA) are plant secondary metabolites with diverse pharmacological properties. To reach reasonable productivities with plant cell suspension cultures, elicitation is a widely used strategy. Within the presented work, the effects of different elicitors on growth and production of OA and UA in a Salvia fruticosa cell suspension culture were examined. Beside commonly used elicitors like jasmonic acid (JA) and yeast extract, the influence of medium filtrates of the endophytic fungi Aspergillus niger and Trichoderma virens was investigated. The best eliciting effects were achieved with JA and fungal medium filtrates. Both increased the triterpene content by approximately 70 %. Since JA showed significant growth inhibition, the volumetric triterpene yield did not increase. But, adding fungal filtrates increased the volumetric triterpene yield by approximately 70 % to 32.6 mgOA l(-1) and 65.9 mgUA l(-1) for T. virens compared to the control with 19.4 mgOA l(-1) and 33.3 mgUA l(-1). An elicitation strategy combining fungal medium filtrate of T. virens with sucrose feeding significantly enhanced cell dry weight concentration to 22.2 g l(-1) as well as triterpene content by approximately 140 %. In total, this led to an approximately 500 % increase of volumetric triterpene yield referring to the control with final values of 112.9 mgOA l(-1) and 210.4 mgUA l(-1). Despite the doubled cultivation duration, productivities of 6.7 mgOA l(-1) day(-1) and 12.4 mgUA l(-1) day(-1) were reached. These results demonstrate methods by which increased productivities of triterpenes can be achieved to attain yields competing with intact plants. PMID:26971493

  10. Significant enhancement of compositional and superconducting homogeneity in Ti rather than Ta-doped Nb3Sn

    NASA Astrophysics Data System (ADS)

    Tarantini, C.; Sung, Z.-H.; Lee, P. J.; Ghosh, A. K.; Larbalestier, D. C.

    2016-01-01

    Nb3Sn wire is now very close to its final optimization, but despite its classical nature, a detailed understanding of the role of Ta and Ti doping in the A15 is not fully developed. Long thought to be essentially equivalent in their influence on Hc2, they were interchangeably applied. Here, we show that Ti produces significantly more homogeneous chemical and superconducting properties. Despite Ta-doped samples having a slightly higher Tc onset in zero-field, they always have a wider Tc-distribution. In particular, whereas the Ta-doped A15 has a Tc-distribution extending from 18 down to 5-6 K (the lowest expected Tc for the binary A15 phase), the Ti-doped samples have no A15 phase with Tc below ˜12 K. The much narrower Tc distribution in the Ti-doped samples has a positive effect on their in-field Tc-distribution too, leading to an extrapolated μ0Hc2(0) 2 T larger than the Ta-doped wire. Ti-doping also appears to be very homogeneous even when the Sn content is reduced in order to inhibit breakdown of the diffusion barriers in very high Jc conductors. The enhanced homogeneity of the Ti-doped samples appears to result from its assistance of rapid diffusion of Sn into the filaments and by its incorporation into the A15 phase interchangeably with Sn on the Sn sites of the A15 phase.

  11. Significant enhancement of photoreactivity of graphitic carbon nitride catalysts under acidic conditions and the underlying H(+)-mediated mechanism.

    PubMed

    Zhang, Xue-Song; Tian, Ke; Hu, Jian-Yang; Jiang, Hong

    2015-12-01

    Graphitic carbon nitride (g-C3N4) is an emerging photocatalyst for organic pollutants degradation owing to its excellent stability and metal-free property. In this study, the photocatalytic activity of acidified g-C3N4 (ag-C3N4) was systematically investigated using rhodamine B (rhB) as a model organic pollutant. The results showed the photoreactivity of ag-C3N4 is significantly enhanced with the decrease of pH values. The apparent rate constant (kapp) of rhB degradation over ag-C3N4 is 11.59×10(-3)min(-1) at pH7.0 and it increases to 103.50×10(-3)min(-1) at pH3.0 under visible light. A series of analyses demonstrate that the photodegradation mechanism is a combination of a H(+)-promoted generation of OH and elevation of the redox potential of conduct band of C3N4. The change of surface properties of C3N4 caused by pH variation also affects the degradation of some zwitterionic compounds by changing the adsorption orientation of pollutants. The revealed mechanism of visible light-C3N4-rhB system is meaningful to broaden the usage of C3N4 to the photodegradation of other organic pollutants. PMID:26172516

  12. Why Sn doping significantly enhances the dielectric properties of Ba(Ti 1-x Snx)O3.

    PubMed

    Shi, Tao; Xie, Lin; Gu, Lin; Zhu, Jing

    2015-01-01

    Through appropriate doping, the properties of BaTiO3-based ferroelectrics can be significantly enhanced. To determine the physical process induced by the doping of Sn atoms in Ba(Ti0.8Sn0.2)O3, we performed high-resolution scanning transmission electron microscopy experiments and observed that the regions with low Sn content formed polar nano regions (PNRs) embedded in the matrix in Ba(Ti0.8Sn0.2)O3. The interactions among Sn, Ti, Ba and O atoms were determined using first principles calculations. Based on the characteristics of the electronic structure and crystal lattice strain fields, the effects of doping with Sn were investigated. The Sn doping not only changed the electronic structure of the crystal but also increased the dielectric properties of the PNRs. Moreover, the Sn doping was also responsible for the diffuse phase transition of the Ba(Ti 1-x Snx)O3 material. The effects mentioned in this paper are universal in lead-free ferroelectrics, and similar elements such as Sb, Mg, and Zr may have the same functions in other systems. Thus, these results provide guidance for the design of the doping process and new systems of ferroelectric or relaxor materials. PMID:25721479

  13. Biocatalytic properties of a recombinant Fusarium proliferatum lactonase with significantly enhanced production by optimal expression in Escherichia coli.

    PubMed

    Chen, Bing; Fan, Li-Qiang; Xu, Jian-He; Zhao, Jian; Zhang, Xian; Ouyang, Li-Ming

    2010-10-01

    The levo-lactonase gene of Fusarium proliferatum ECU2002 (EC3.1.1.25) was cloned and expressed in Escherichia coli JM109 (DE3) for biocatalytic resolution of industrially important chiral lactones, including DL-pantoyl lactone which was a key precursor to calcium D-pantothenate. By increasing the biomass concentration and lowering the inducer (isopropyl-beta-D-thiogalactoside) concentration and induction temperature, the lactonase production was significantly enhanced up to 20 kU/L, which was 20 times higher than that of wild-type strain F. proliferatum ECU2002. The recombinant Fusarium lactonase was purified using immobilized metal affinity chromatography, and its SDS-PAGE revealed a molecular mass of 50 kDa for the recombinant protein, suggesting that the enzyme was a simplex protein. Furthermore, biocatalytic properties of the recombinant lactonase were investigated, including kinetic parameters, additive's effect, and substrate specificity. The results reported in this paper provide a feasible method to make the whole cells of E. coli JM109 (DE3) expressing lactonase gene to be a highly efficient and easy-to-make biocatalyst for asymmetric synthesis of chiral compounds. PMID:19876606

  14. The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides.

    PubMed

    Zhi, Duo; Feng, Pan-Feng; Sun, Jia-Liang; Guo, Fengfeng; Zhang, Rui; Zhao, Xin; Li, Bao-Xin

    2015-08-30

    As is well-known, hERG plays an essential role in phase III repolarization of cardiac action potentials. Blocking of hERG channels can lead to LQTS. Inhibition of the metabolism of CYPs activities may elevate plasma levels, to further increase accumulation of drug on cardiac. The elevated serum levels may however elicit unexpected toxicities. Therefore, the inhibition tests of hERG and CYP are central to the preclinical studies because they may lead to severe cardiac toxicity. Berberine is widely used as an antibacterial agent and often combined with macrolides to treat gastropathy. Our objective was to assess cardiac toxicity during the combined use of Berberine with macrolides. (1) Azithromycin reduced hERG currents by accelerated channel inactivation. (2) The combination of Berberine with Azithromycin reduced hERG currents, producing an inhibitive effect stronger than use of a single drug alone, due to the high binding affinity for the onset of inactivation. (3) When cells were perfused concomitantly with Berberine and Clarithromycin, they showed a stronger inhibitive effect on hERG currents by decreasing the time constant for the onset of inactivation. (4) The combined administration of Berberine with Clarithromycin had a powerful inhibitive effect on CYP3A activities than use of a single drug alone. Collectively, these results demonstrated that concomitant use of Berberine with macrolides may require close monitoring because of potential drug toxicities, especially cardiac toxicity. PMID:25976224

  15. Mass Administration of Ivermectin for the Elimination of Onchocerciasis Significantly Reduced and Maintained Low the Prevalence of Strongyloides stercoralis in Esmeraldas, Ecuador

    PubMed Central

    Anselmi, Mariella; Buonfrate, Dora; Guevara Espinoza, Angel; Prandi, Rosanna; Marquez, Monica; Gobbo, Maria; Montresor, Antonio; Albonico, Marco; Racines Orbe, Marcia; Bisoffi, Zeno

    2015-01-01

    Objectives To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases. Methods We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis). Results In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%. In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults. Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected. Conclusions Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections. PMID:26540412

  16. Repeated cocaine administration decreases calcineurin (PP2B) but enhances DARPP-32 modulation of sodium currents in rat nucleus accumbens neurons.

    PubMed

    Hu, Xiu-Ti; Ford, Kerstin; White, Francis J

    2005-05-01

    Our previous studies have demonstrated that repeated cocaine (COC) administration reduces voltage-sensitive sodium and calcium currents (I(Na) or VSSCs and I(Ca) or VSCCs, respectively) in medium spiny nucleus accumbens (NAc) neurons of rats. The present findings further indicate that chronic COC-induced I(Na) reduction in NAc neurons is regulated by decreased dephosphorylation and enhanced phosphorylation of Na(+) channels. Whole-cell voltage-clamp recordings revealed that dephosphorylation of Na(+) channels by calcineurin (CaN) enhanced I(Na), while inhibition of protein phosphatase 1 (PP1) by phosphorylated dopamine- and cAMP-regulated phosphoprotein (M(r)=32 kDa) (DARPP-32) at the site of threonine 34 (p-Thr.34-DARPP-32) suppressed I(Na), in freshly dissociated NAc neurons of saline-pretreated rats. However, the effects of CaN on enhancing I(Na) were significantly attenuated, and the action of p-Thr.34-DARPP-32 to decrease I(Na) was mimicked, although not potentiated, by repeated COC pretreatment. Dephosphorylation of Na(+) channels by PP1 also enhanced I(Na), but this effect of PP1 on I(Na) was not apparently affected by repeated COC administration. Western blot analysis indicates that the protein levels of CaN and DARPP-32 were significantly decreased and increased, respectively, while the PP1 levels were unchanged, in the COC-withdrawn NAc as compared to saline-pretreated controls. Combined with previous findings, our results indicate that both CaN and PP1 modulate the increase in I(Na) via enhancing dephosphorylation, while p-Thr.34-DARPP-32 reduces I(Na) by inhibiting PP1-induced dephosphorylation, thereby stabilizing the phosphorylation state, of Na(+) channels in NAc neurons. They also suggest that chronic COC-induced I(Na) reduction may be attributed to a reduction in Ca(2+) signaling, which disrupts the physiological balance of phosphorylation and dephosphorylation of Na(+) channels. PMID:15726118

  17. SYSTEMIC ADMINISTRATION OF BORDETELLA PERTUSSIS ENHANCES PULMONARY SENSITIZATION TO HOUSE DUST MITE IN JUVENILE RATS

    EPA Science Inventory

    The incidence of allergies and asthma has increased significantly in the past few decades. The objectives of this study were to establish an allergy model in weanling rats to more closely reflect the developing immune system of children, and to determine whether systemic administ...

  18. Thiolated polycarbophil/glutathione: defining its potential as a permeation enhancer for oral drug administration in comparison to sodium caprate.

    PubMed

    Perera, Glen; Barthelmes, Jan; Vetter, Anja; Krieg, Christof; Uhlschmied, Cindy; Bonn, Günther K; Bernkop-Schnürch, Andreas

    2011-08-01

    Thiolated polyacrylates were shown to be permeation enhancers with notable potential. The aim of this study was to evaluate the permeation enhancing properties of a thiolated polycarbophil/glutathione (PCP-Cys/GSH) system for oral drug application in comparison to a well-established permeation enhancer, namely sodium caprate. In vitro permeation studies were conducted in Ussing-type chambers with sodium fluoresceine (NaFlu) and fluoresceine isothiocyanate labeled dextran (molecular mass 4 kDa; FD4) as model compounds. Bioavailability studies were carried out in Sprague Dawley rats with various formulations. Moreover, cytotoxic effects of both permeation enhancers were compared. Permeation enhancement ratios of 1% sodium caprate were found to be 3.0 (FD4) and 2.3 (NaFlu), whereas 1% PCP-Cys/0.5% GSH displayed enhancement ratios of 2.4 and 2.2. Both excipients performed at a similar level in vivo. Sodium caprate solutions increased oral bioavailability 2.2-fold (FD4) and 2.3-fold (NaFlu), while PCP-Cys hydrogels led to a 3.2-fold and 2.2-fold enhancement. Cell viability experiments revealed a significantly higher tolerance of Caco-2 cells towards 0.5% PCP-Cys (81% survival) compared to 0.5% sodium caprate (5%). As PCP-Cys is not absorbed from mucosal membranes due to its comparatively high molecular mass, systemic side-effects can be excluded. In conclusion, both systems displayed a similar potency for permeation enhancement of hydrophilic compounds. However, PCP-Cys seems to be less harmful to cultured cells. PMID:21554106

  19. Enhanced self-administration of alcohol in muscarinic acetylcholine M4 receptor knockout mice.

    PubMed

    de la Cour, Cecilie; Sørensen, Gunnar; Wortwein, Gitta; Weikop, Pia; Dencker, Ditte; Fink-Jensen, Anders; Molander, Anna

    2015-01-01

    Modulation of cholinergic neurotransmission via nicotinic acetylcholine receptors is known to alter alcohol-drinking behavior. It is not known if muscarinic acetylcholine receptor subtypes have similar effects. The muscarinic M4 receptor is highly expressed in the brain reinforcement system and involved in regulation of cholinergic and dopaminergic transmission. Here we investigate, for the first time, the role of the M4 receptor in alcohol consumption using M4 knockout (M4(-/-)) and wild-type (M4(+/+)) mice. Experimentally naïve M4(-/-) and M4(+/+) mice were trained to orally self-administer 5%, 8% and 10% alcohol in 60min sessions, 6 days/week, after having undergone a standard sucrose fading training procedure on a fixed ratio schedule. The mice were further subjected to an extinction period followed by a 1 day reinstatement trial. M4(-/-) mice consumed more alcohol at 5% and 8% compared to their M4(+/+) littermates. The highest alcohol concentration used (10%) did not immediately result in divergent drinking patterns, but after 4 weeks of 10% alcohol self-administration, baseline levels as well as a pattern of M4(-/-) mice consuming more alcohol than their M4(+/+) controls were re-established. Moreover, the M4(-/-) mice displayed a reduced capacity to extinguish their alcohol-seeking behavior. Taken together, alcohol consumption is elevated in M4(-/-) mice, indicating that the M4 receptor is involved in mediating the reinforcing effects of alcohol. The M4 receptor should be further explored as a potential target for pharmacological (positive allosteric modulators or future agonists) treatment of alcohol use disorders. PMID:25445043

  20. Role of amphotericin B upon enhancement of protective immunity elicited by oral administration with liposome-encapsulated-Japanese encephalitis virus nonstructural protein 1 (NS1) in mice.

    PubMed

    Lin, Tsung-Shun; Chuang, Chuan-Chang; Hsu, Hui-Ling; Liu, Yu-Tien; Lin, Wen-Po; Liang, Chung-Chih; Liu, Wen-Tssann

    2010-09-01

    Amphotericin B (AmB) is an antifungal antibiotic the activity of which has been associated with modulation of pro-inflammatory cytokines expression in cultured cells. Herein we reveal that co-administration with AmB enhances the immunogenicity of oral Lip-JENS1 vaccine which derived from liposomes functionalized with DSPC (distearoylphosphatidylcholine) and cholesterol (2:1, molar ratio)-bearing JE virus NS1 protein (600 microg ml(-1)). Oral single dose of Lip-JENS1 elicited a detectable serum NS1-specific IgG antibody response from a mouse model. Remarkably, the addition of AmB (125 microg per mouse), particularly, 2 h prior to, but not simultaneously with, the administration of Lip-JENS1 significantly enhanced the systemic antigen-specific antibody response, providing superior protection against lethal JEV challenges. Further, we observed AmB-induced the transcription of cytokine expression and translocation of transcriptional factor NF-kappaB from the cytoplasm to the nucleus for the murine macrophage J774A.1. Moreover, Peyer's-patch lymphocytes (PPL) from AmB-treated mice produced high levels of IL-1beta, IL-6 and TNF-alpha expression compared to the corresponding control of cells from non-treated mice. Taken together, the results suggest that AmB exerts a profound influence upon mucosal vaccination with Lip-JENS1, possibly playing an adjuvant-augmented role to "fine-tune" humoral as well as cellular immune response, thus conferring enhanced protective immunity for immunising individuals against JE infection. PMID:20412849

  1. Adjuvant and immunostimulatory effects of beta-glucan administration in combination with lipopolysaccharide enhances survival and some immune parameters in carp challenged with Aeromonas hydrophila.

    PubMed

    Selvaraj, V; Sampath, K; Sekar, Vaithilingam

    2006-11-15

    Combined effects of beta-glucan and lipopolysaccharide (LPS) on survival and immune response were studied in Cyprinus carpio that were challenged with the pathogen Aeromonas hydrophila. beta-Glucan from Saccharomyces cervisiae and LPS from a virulent strain of A. hydrophila were used in this study. Different concentrations of beta-glucan+LPS mixture were administered on days 1, 7, and 14 through different routes (intraperitoneal injection, bathing, and oral administration). Control and test fish were challenged by intraperitoneal injection of LD50 concentration of A. hydrophila on day 16 and subsequently, mortality and relative percent survival (RPS) were recorded. Intraperitoneal injection elicited 100% RPS even at the lowest concentration (100 microg beta-glucan+10 microg LPS); whereas, oral administration improved RPS rate of carps at higher concentration (1% beta-glucan+0.25% LPS). Bathing did not improve the RPS. Test animals injected with even the minimum dose of the immunomodulators (100 microg beta-glucan+10 microg LPS/fish) had a significant increase in total blood leukocyte counts and an increase in the proportion of neutrophils and monocytes. Superoxide anion production by macrophages was also elevated, which presumably aided the efficient killing of bacterial pathogen. Lower concentration of beta-glucan+LPS had an adjuvant effect on antibody production as pretreatment by injection of 100 microg beta-glucan+10 microg LPS/fish resulted in higher antibody titer against A. hydrophila following vaccination. RT-PCR analyses showed that the expression of interleukin-1beta mRNA did not increase in test fish when compared with the control. Classical and alternative complement pathways were not affected by either the dose or the route of administration of the compounds. It may be concluded that intraperitoneal injection and oral administration, and not the bathing, of beta-glucan+LPS mixture in carp could enhance resistance to challenge by A. hydrophila through

  2. Enhancing Neoplasm Expression in Field Pea (Pisum sativum) via Intercropping and Its Significance to Pea Weevil (Bruchus pisorum) Management.

    PubMed

    Teshome, Abel; Bryngelsson, Tomas; Mendesil, Esayas; Marttila, Salla; Geleta, Mulatu

    2016-01-01

    Neoplasm formation, a non-meristematic tissue growth on young field pea (Pisum sativum L.) pods is triggered in the absence of UV light and/or in response to oviposition by pea weevil (Bruchus pisorum L.). This trait is expressed in some genotypes [neoplastic (Np) genotypes] of P. sativum and has the capacity to obstruct pea weevil larval entry into developing seeds. In the present study, 26% of the tested accessions depicted the trait when grown under greenhouse conditions. However, UV light inhibits full expression of this trait and subsequently it is inconspicuous at the field level. In order to investigate UV light impact on the expression of neoplasm, particular Np genotypes were subjected to UV lamp light exposure in the greenhouse and sunlight at the field level. Under these different growing conditions, the highest mean percentage of Np pods was in the control chamber in the greenhouse (36%) whereas in single and double UV lamp chambers, the percentage dropped to 10 and 15%, respectively. Furthermore, when the same Np genotypes were grown in the field, the percentage of Np pods dropped significantly (7%). In order to enhance Np expression at the field level, intercropping of Np genotypes with sorghum was investigated. As result, the percentage of Np pods was threefold in intercropped Np genotypes as compared to those without intercropping. Therefore, intercropping Np genotypes with other crops such as sorghum and maize can facilitate neoplasm formation, which in turn can minimize the success rate of pea weevil larvae entry into developing seeds. Greenhouse artificial infestation experiments showed that pea weevil damage in Np genotypes is lower in comparison to wild type genotypes. Therefore, promoting Np formation under field conditions via intercropping can serve as part of an integrated pea weevil management strategy especially for small scale farming systems. PMID:27242855

  3. Enhancing Neoplasm Expression in Field Pea (Pisum sativum) via Intercropping and Its Significance to Pea Weevil (Bruchus pisorum) Management

    PubMed Central

    Teshome, Abel; Bryngelsson, Tomas; Mendesil, Esayas; Marttila, Salla; Geleta, Mulatu

    2016-01-01

    Neoplasm formation, a non-meristematic tissue growth on young field pea (Pisum sativum L.) pods is triggered in the absence of UV light and/or in response to oviposition by pea weevil (Bruchus pisorum L.). This trait is expressed in some genotypes [neoplastic (Np) genotypes] of P. sativum and has the capacity to obstruct pea weevil larval entry into developing seeds. In the present study, 26% of the tested accessions depicted the trait when grown under greenhouse conditions. However, UV light inhibits full expression of this trait and subsequently it is inconspicuous at the field level. In order to investigate UV light impact on the expression of neoplasm, particular Np genotypes were subjected to UV lamp light exposure in the greenhouse and sunlight at the field level. Under these different growing conditions, the highest mean percentage of Np pods was in the control chamber in the greenhouse (36%) whereas in single and double UV lamp chambers, the percentage dropped to 10 and 15%, respectively. Furthermore, when the same Np genotypes were grown in the field, the percentage of Np pods dropped significantly (7%). In order to enhance Np expression at the field level, intercropping of Np genotypes with sorghum was investigated. As result, the percentage of Np pods was threefold in intercropped Np genotypes as compared to those without intercropping. Therefore, intercropping Np genotypes with other crops such as sorghum and maize can facilitate neoplasm formation, which in turn can minimize the success rate of pea weevil larvae entry into developing seeds. Greenhouse artificial infestation experiments showed that pea weevil damage in Np genotypes is lower in comparison to wild type genotypes. Therefore, promoting Np formation under field conditions via intercropping can serve as part of an integrated pea weevil management strategy especially for small scale farming systems. PMID:27242855

  4. Significant enhancement of compositional and superconducting homogeneity in Ti rather than Ta-doped Nb3Sn

    DOE PAGESBeta

    Tarantini, C.; Sung, Z. -H.; Lee, P. J.; Ghosh, A. K.; Larbalestier, D. C.

    2016-01-25

    Nb3Sn wires are now very close to their final optimization but despite its classical nature, detailed understanding of the role of Ta and Ti doping in the A15 is not fully understood. Long thought to be essentially equivalent in their influence on Hc2, they were interchangeably applied. Here we show that Ti produces significantly more homogeneous chemical and superconducting properties. Despite Ta-doped samples having a slightly higher Tc onset in zero-field, they always have a wider Tc-distribution. In particular, whereas the Ta-doped A15 has a Tc-distribution extending from 18 down to 5-6 K (the lowest expected Tc for the binarymore » A15 phase), the Ti-doped samples have no A15 phase with Tc below ~12 K. The much narrower Tc distribution in the Ti-doped samples has a positive effect on their in-field Tc-distribution too, leading to an extrapolated μ0Hc2(0) 2 Tesla larger than the Ta-doped one. Ti-doping also appears to be very homogeneous even when the Sn content is reduced in order to inhibit breakdown of the diffusion barriers in very high Jc conductors. As a result, the enhanced homogeneity of the Ti-doped samples appears to result from its assistance of rapid diffusion of Sn into the filaments and by its incorporation into the A15 phase interchangeably with Sn on the Sn sites of the A15 phase.« less

  5. Systemic administration of IGF-I enhances healing in collagenous extracellular matrices: evaluation of loaded and unloaded ligaments

    PubMed Central

    Provenzano, Paolo P; Alejandro-Osorio, Adriana L; Grorud, Kelley W; Martinez, Daniel A; Vailas, Arthur C; Grindeland, Richard E; Vanderby, Ray

    2007-01-01

    Background Insulin-like growth factor-I (IGF-I) plays a crucial role in wound healing and tissue repair. We tested the hypotheses that systemic administration of IGF-I, or growth hormone (GH), or both (GH+IGF-I) would improve healing in collagenous connective tissue, such as ligament. These hypotheses were examined in rats that were allowed unrestricted activity after injury and in animals that were subjected to hindlimb disuse. Male rats were assigned to three groups: ambulatory sham-control, ambulatory-healing, and hindlimb unloaded-healing. Ambulatory and hindlimb unloaded animals underwent surgical disruption of their knee medial collateral ligaments (MCLs), while sham surgeries were performed on control animals. Healing animals subcutaneously received systemic doses of either saline, GH, IGF-I, or GH+IGF-I. After 3 weeks, mechanical properties, cell and matrix morphology, and biochemical composition were examined in control and healing ligaments. Results Tissues from ambulatory animals receiving only saline had significantly greater strength than tissue from saline receiving hindlimb unloaded animals. Addition of IGF-I significantly improved maximum force and ultimate stress in tissues from both ambulatory and hindlimb unloaded animals with significant increases in matrix organization and type-I collagen expression. Addition of GH alone did not have a significant effect on either group, while addition of GH+IGF-I significantly improved force, stress, and modulus values in MCLs from hindlimb unloaded animals. Force, stress, and modulus values in tissues from hindlimb unloaded animals receiving IGF-I or GH+IGF-I exceeded (or were equivalent to) values in tissues from ambulatory animals receiving only saline with greatly improved structural organization and significantly increased type-I collagen expression. Furthermore, levels of IGF-receptor were significantly increased in tissues from hindlimb unloaded animals treated with IGF-I. Conclusion These results

  6. Parenteral Administration of l-Arginine Enhances Fetal Survival and Growth in Sheep Carrying Multiple Fetuses123

    PubMed Central

    Lassala, Arantzatzu; Bazer, Fuller W.; Cudd, Timothy A.; Datta, Sujay; Keisler, Duane H.; Satterfield, M. Carey; Spencer, Thomas E.; Wu, Guoyao

    2011-01-01

    The frequency of multiple fetuses has increased in human pregnancies due to assisted reproductive technologies. This translates into a greater proportion of premature and low-birth weight infants in the United States and worldwide. In addition, improvements in sheep breeding have resulted in new breeds with increased litter size but reduced fetal survival and birth weight. Currently, there are no treatments for preventing fetal growth restriction in humans or sheep (an established model for studying human fetal physiology) carrying multiple fetuses. In this work, Booroola Rambouillet ewes (FecB+/−) with 2–4 fetuses were fed a diet providing 100% of NRC-recommended nutrient requirements. Between d 100 and 121 of gestation, ewes received an i.v. bolus injection of either saline solution or 345 μmol arginine-HCl/kg body weight 3 times daily. The arginine treatment reduced (P < 0.05) the percentage of lambs born dead by 23% while increasing (P = 0.05) the percentage of lambs born alive by 59%. The i.v. administration of arginine enhanced (P < 0.05) the birth weights of quadruplets by 23% without affecting maternal body weight. The improved pregnancy outcome was associated with an increase in maternal plasma concentrations of arginine, ornithine, cysteine, and proline, as well as a decrease in circulating levels of ammonia and β-hydroxybutyrate. These novel results indicate that parenteral administration of arginine to prolific ewes ameliorated fetal mortality and growth retardation. Our findings provide support for experiments to assess the clinical use of arginine to enhance fetal growth and survival in women gestating multiple fetuses. PMID:21430253

  7. Chronic administration of a microencapsulated probiotic enhances the bioavailability of orange juice flavanones in humans.

    PubMed

    Pereira-Caro, Gema; Oliver, Christine M; Weerakkody, Rangika; Singh, Tanoj; Conlon, Michael; Borges, Gina; Sanguansri, Luz; Lockett, Trevor; Roberts, Susan A; Crozier, Alan; Augustin, Mary Ann

    2015-07-01

    Orange juice (OJ) flavanones are bioactive polyphenols that are absorbed principally in the large intestine. Ingestion of probiotics has been associated with favorable changes in the colonic microflora. The present study examined the acute and chronic effects of orally administered Bifidobacterium longum R0175 on the colonic microflora and bioavailability of OJ flavanones in healthy volunteers. In an acute study volunteers drank OJ with and without the microencapsulated probiotic, whereas the chronic effects were examined when OJ was consumed after daily supplementation with the probiotic over 4 weeks. Bioavailability, assessed by 0-24h urinary excretion, was similar when OJ was consumed with and without acute probiotic intake. Hesperetin-O-glucuronides, naringenin-O-glucuronides, and hesperetin-3'-O-sulfate were the main urinary flavanone metabolites. The overall urinary excretion of these metabolites after OJ ingestion and acute probiotic intake corresponded to 22% of intake, whereas excretion of key colon-derived phenolic and aromatic acids was equivalent to 21% of the ingested OJ (poly)phenols. Acute OJ consumption after chronic probiotic intake over 4 weeks resulted in the excretion of 27% of flavanone intake, and excretion of selected phenolic acids also increased significantly to 43% of (poly)phenol intake, corresponding to an overall bioavailability of 70%. Neither the probiotic bacterial profiles of stools nor the stool moisture, weight, pH, or levels of short-chain fatty acids and phenols differed significantly between treatments. These findings highlight the positive effect of chronic, but not acute, intake of microencapsulated B. longum R0175 on the bioavailability of OJ flavanones. PMID:25801290

  8. Significant enhancement in photocatalytic reduction of water to hydrogen by Au/Cu2 ZnSnS4 nanostructure.

    PubMed

    Ha, Enna; Lee, Lawrence Yoon Suk; Wang, Jingchuan; Li, Fenghua; Wong, Kwok-Yin; Tsang, Shik Chi Edman

    2014-06-01

    Enhanced photocatalytic activities by Au core Novel Au/Cu2 ZnSnS4 core/shell nanoparticles (NPs) are synthesized for the first time via wet chemistry approach. The insertion of Au core into CZTS NPs dramatically enhances light absorption due to surface plasmon resonance effect, especially in the Vis-NIR region. Au/CZTS core/shell NPs show much higher photocatalytic activities for hydrogen evolution compared with other CZTS nanostructures. PMID:24644004

  9. Significant Enhancement of the Chiral Correlation Length in Nematic Liquid Crystals by Gold Nanoparticle Surfaces Featuring Axially Chiral Binaphthyl Ligands.

    PubMed

    Mori, Taizo; Sharma, Anshul; Hegmann, Torsten

    2016-01-26

    surface is diminished as the size of the particle is reduced. However, in comparison to the free ligands, per chiral molecule all tested gold nanoparticles induce helical distortions in a 10- to 50-fold larger number of liquid crystal host molecules surrounding each particle, indicating a significantly enhanced chiral correlation length. We propose that both the helicity and the chirality transfer efficiency of axially chiral binaphthyl derivatives can be controlled at metal nanoparticle surfaces by adjusting the particle size and curvature as well as the number and density of the chiral ligands to ultimately measure and tune the chiral correlation length. PMID:26735843

  10. Enhanced protective immune response to PCV2 subunit vaccine by co-administration of recombinant porcine IFN-γ in mice.

    PubMed

    Wang, Yi-Ping; Liu, Dan; Guo, Long-Jun; Tang, Qing-Hai; Wei, Yan-Wu; Wu, Hong-Li; Liu, Jian-Bo; Li, Sheng-Bin; Huang, Li-Ping; Liu, Chang-Ming

    2013-01-21

    The capsid (Cap) protein of PCV2 is the major immunogenic protein that is crucial to induce PCV2-specific neutralizing antibodies and protective immunity; thus, it is a suitable target antigen for the research and development of genetically engineered vaccines against PCV2 infection. IFN-γ has exhibited potential efficacy as an immune adjuvant that enhances the immunogenicity of certain vaccines in experimental animal models. In this study, three recombinant proteins: PCV2-Cap protein, porcine IFN-γ (PoIFN-γ), and the fusion protein (Cap-PoIFN-γ) of PCV2-Cap protein and PoIFN-γ were respectively expressed in the baculovirus system, and analyzed by Western blot and indirect ELISA. Additionally, we evaluated the enhancement of the protective immune response to the Cap protein-based PCV2 subunit vaccine elicited by co-administration of PoIFN-γ in mice. Vaccination of mice with the PCV2-Cap+PoIFN-γ vaccine elicited significantly higher levels of PCV2-specific IPMA antibodies, neutralizing antibodies, and lymphocyte proliferative responses compared to the Cap-PoIFN-γ vaccine, the PCV2-Cap vaccine, and LG-strain. Following virulent PCV2 challenge, no viraemia was detected in all immunized groups, and the viral loads in lungs of the PCV2-Cap+PoIFN-γ group were significantly lower compared to the Cap-PoIFN-γ group, the LG-strain group, and the mock group, but slightly lower compared to the PCV2-Cap group. These findings suggested that PoIFN-γ substantially enhanced the protective immune response to the Cap protein-based PCV2 subunit vaccine, and that the PCV2-Cap+PoIFN-γ subunit vaccine potentially serves as an attractive candidate vaccine for the prevention and control of PCV2-associated diseases. PMID:23219694

  11. A significant increase of RNAi efficiency in human cells by the CMV enhancer with a tRNAlys promoter.

    PubMed

    Weiwei, Ma; Zhenhua, Xie; Feng, Liu; Hang, Ning; Yuyang, Jiang

    2009-01-01

    RNA interference (RNAi) is the process of mRNA degradation induced by double-stranded RNA in a sequence-specific manner. Different types of promoters, such as U6, H1, tRNA, and CMV, have been used to control the inhibitory effect of RNAi expression vectors. In the present study, we constructed two shRNA expression vectors, respectively, controlled by tRNA(lys) and CMV enhancer-tRNA(lys) promoters. Compared to the vectors with tRNA(lys) or U6 promoter, the vector with a CMV enhancer-tRNA(lys) promoter silenced pokemon more efficiently on both the mRNA and the protein levels. Meanwhile, the silencing of pokemon inhibited the proliferation of MCF7 cells, but the induction of apoptosis of MCF7 cells was not observed. We conclude that the CMV enhancer-tRNA(lys) promoter may be a powerful tool in driving intracellular expression of shRNA which can efficiently silence targeted gene. PMID:19859553

  12. A Significant Increase of RNAi Efficiency in Human Cells by the CMV Enhancer with a tRNAlys Promoter

    PubMed Central

    Weiwei, Ma; Zhenhua, Xie; Feng, Liu; Hang, Ning; Yuyang, Jiang

    2009-01-01

    RNA interference (RNAi) is the process of mRNA degradation induced by double-stranded RNA in a sequence-specific manner. Different types of promoters, such as U6, H1, tRNA, and CMV, have been used to control the inhibitory effect of RNAi expression vectors. In the present study, we constructed two shRNA expression vectors, respectively, controlled by tRNAlys and CMV enhancer-tRNAlys promoters. Compared to the vectors with tRNAlys or U6 promoter, the vector with a CMV enhancer-tRNAlys promoter silenced pokemon more efficiently on both the mRNA and the protein levels. Meanwhile, the silencing of pokemon inhibited the proliferation of MCF7 cells, but the induction of apoptosis of MCF7 cells was not observed. We conclude that the CMV enhancer-tRNAlys promoter may be a powerful tool in driving intracellular expression of shRNA which can efficiently silence targeted gene. PMID:19859553

  13. Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms

    PubMed Central

    Amchova, Petra; Kucerova, Jana; Giugliano, Valentina; Babinska, Zuzana; Zanda, Mary T.; Scherma, Maria; Dusek, Ladislav; Fadda, Paola; Micale, Vincenzo; Sulcova, Alexandra; Fratta, Walter; Fattore, Liana

    2013-01-01

    Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed altered voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 μg/kg/infusion). To this aim, olfactory-bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)] schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behavior after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5–10 mg/kg), did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive-like state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats. PMID:24688470

  14. Docosahexaenoic Acid Conjugation Enhances Distribution and Safety of siRNA upon Local Administration in Mouse Brain.

    PubMed

    Nikan, Mehran; Osborn, Maire F; Coles, Andrew H; Godinho, Bruno Mdc; Hall, Lauren M; Haraszti, Reka A; Hassler, Matthew R; Echeverria, Dimas; Aronin, Neil; Khvorova, Anastasia

    2016-01-01

    The use of siRNA-based therapies for the treatment of neurodegenerative disease requires efficient, nontoxic distribution to the affected brain parenchyma, notably the striatum and cortex. Here, we describe the synthesis and activity of a fully chemically modified siRNA that is directly conjugated to docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the mammalian brain. DHA conjugation enables enhanced siRNA retention throughout both the ipsilateral striatum and cortex following a single, intrastriatal injection (ranging from 6-60 μg). Within these tissues, DHA conjugation promotes internalization by both neurons and astrocytes. We demonstrate efficient and specific silencing of Huntingtin mRNA expression in both the ipsilateral striatum (up to 73%) and cortex (up to 51%) after 1 week. Moreover, following a bilateral intrastriatal injection (60 μg), we achieve up to 80% silencing of a secondary target, Cyclophilin B, at both the mRNA and protein level. Importantly, DHA-hsiRNAs do not induce neural cell death or measurable innate immune activation following administration of concentrations over 20 times above the efficacious dose. Thus, DHA conjugation is a novel strategy for improving siRNA activity in mouse brain, with potential to act as a new therapeutic platform for the treatment of neurodegenerative disorders. PMID:27504598

  15. In vivo administration of recombinant growth hormone or gamma interferon activities macrophages: enhanced resistance to experimental Salmonella typhimurium infection is correlated with generation of reactive oxygen intermediates.

    PubMed Central

    Edwards, C K; Ghiasuddin, S M; Yunger, L M; Lorence, R M; Arkins, S; Dantzer, R; Kelley, K W

    1992-01-01

    Purified and recombinant forms of growth hormone (GH) as well as of recombinant rat gamma interferon (IFN-gamma) enhance the survival of rats deprived of endogenous pituitary GH secretion by hypophysectomy (HX rats) and infected with virulent Salmonella typhimurium. Macrophages obtained from rats with intact pituitaries (pituitary-intact rats) or HX rats that were treated in vivo with either GH or the closely related hormone prolactin released elevated (P less than 0.05) levels of superoxide anion (O2-) after in vitro opsonized-zymosan stimulation compared with those from placebo-treated animals. These levels of O2- release were similar in magnitude to those of macrophages from rats treated in vivo with IFN-gamma. In time course in vivo macrophage activation studies, both IFN-gamma and GH significantly increased O2- secretion within 24 h, with maximal secretion occurring at day 3. Macrophages obtained from pituitary-intact and HX rats injected in vivo with GH also released elevated (P less than 0.05) levels of hydrogen peroxide (H2O2) and displayed enhanced (P less than 0.01) phagocytic activity toward opsonized Listeria monocytogenes in vitro. The mechanism of action of GH in vivo is likely to be a direct one because resident peritoneal macrophages from rats could be primed in vitro for enhanced secretion of O2- following triggering of these cells with opsonized zymosan. These data show that in vivo administration of two closely related pituitary hormones, GH and prolactin, can effectively prime macrophages, which is consistent with the hypothesis that GH mediates resistance to S. typhimurium by a direct stimulatory action on macrophages. PMID:1316877

  16. Hydrogenation of Ferrimagnetic Graphene on a Co Surface: Significant Enhancement of Spin Moments by C-H Functionality.

    PubMed

    Kaul, Indu; Joshi, Niharika; Ballav, Nirmalya; Ghosh, Prasenjit

    2012-09-20

    Using ab initio density functional theory, we present a novel way of simultaneously enhancing the induced magnetic moment and opening up the band gap of a graphene sheet supported on ferromagnetic transition metal surface. Specifically, we have demonstrated that by simply hydrogenating graphene supported on ferromagnetic Co surface at saturation coverage, (i) there is a six-fold increase in the magnitude of the induced magnetic moment compared with the pristine graphene on the Co surface and (ii) for both the spin-up and the spin-down channels there is a band gap opening at the K-point of the Brillouin zone. PMID:26295878

  17. Cranial magnetic resonance imaging findings of leptomeningeal contrast enhancement after pediatric posterior fossa tumor resection and its significance.

    PubMed

    Loree, Jonathan; Mehta, Vivek; Bhargava, Ravi

    2010-07-01

    In this report, the authors illustrate the potential shortfalls of early postoperative MR imaging following resection of a posterior fossa tumor. The authors present the cases of a 10-month-old boy and a 14-year-old boy with posterior fossa tumors that were surgically resected and monitored immediately postoperatively with MR imaging. The MR imaging study obtained immediately postresection while the children were still anesthetized revealed enhancing elements in both patients, which were suggestive of leptomeningeal metastases. When this signal was followed on subsequent MR images, it was no longer visible. The patients are both recurrence free at the time of this publication. These cases demonstrate that early postoperative MR imaging findings for leptomeningeal metastases may be unreliable after excision of posterior fossa tumors and may have potential implications for intraoperative MR imaging techniques currently under development. PMID:20593993

  18. Explosives sensing by using electron-rich supramolecular polymers: role of intermolecular hydrogen bonding in significant enhancement of sensitivity.

    PubMed

    Gole, Bappaditya; Song, Wentao; Lackinger, Markus; Mukherjee, Partha Sarathi

    2014-10-13

    We demonstrate here that supramolecular interactions enhance the sensitivity towards detection of electron-deficient nitro-aromatic compounds (NACs) over discrete analogues. NACs are the most commonly used explosive ingredients and are common constituents of many unexploded landmines used during World War II. In this study, we have synthesised a series of pyrene-based polycarboxylic acids along with their corresponding discrete esters. Due to the electron richness and the fluorescent behaviour of the pyrene moiety, all the compounds act as sensors for electron-deficient NACs through a fluorescence quenching mechanism. A Stern-Volmer quenching constant determination revealed that the carboxylic acids are more sensitive than the corresponding esters towards NACs in solution. The high sensitivity of the acids was attributed to supramolecular polymer formation through hydrogen bonding in the case of the acids, and the enhancement mechanism is based on an exciton energy migration upon excitation along the hydrogen-bond backbone. The presence of intermolecular hydrogen bonding in the acids in solution was established by solvent-dependent fluorescence studies and dynamic light scattering (DLS) experiments. In addition, the importance of intermolecular hydrogen bonds in solid-state sensing was further explored by scanning tunnelling microscopy (STM) experiments at the liquid-solid interface, in which structures of self-assembled monolayer of the acids and the corresponding esters were compared. The sensitivity tests revealed that these supramolecular sensors can even detect picric acid and trinitrotoluene in solution at levels as low as parts per trillion (ppt), which is much below the recommended permissible level of these constituents in drinking water. PMID:25187022

  19. Carbonization of self-assembled nanoporous hemin with a significantly enhanced activity for the oxygen reduction reaction.

    PubMed

    Xie, Yan; Tang, Chizhou; Hao, Zhiqiang; Lv, Yang; Yang, Ruixia; Wei, Xuming; Deng, Weiqiao; Wang, Anjie; Yi, Baolian; Song, Yujiang

    2014-01-01

    The scarcity and high cost of Pt-based electrocatalysts for the oxygen reduction reaction (ORR) hinder the practical application of proton exchange membrane fuel cells (PEMFCs). It is critical to replace platinum with non-noble metal electrocatalysts (NNMEs). Carbonized metalloporphyrins represent an important class of NNMEs, but most metalloporphyrins are costly and the corresponding NNMEs do not possess a high ORR activity. Herein, we report that the self-assembly of inexpensive hemin leads to porous nanomaterials in water under ambient conditions and subsequent heat-treatment of the unprecedented nanoporous hemin results in a magnetic NNME with a much enhanced ORR activity compared with directly carbonized hemin without self-assembly. The improvement of the ORR activity likely originates from the exposure of more ORR active sites, caused by the surface area increase of the nanoporous hemin after carbonization over that of micro-scale pristine hemin crystals. Moreover, the ORR activity of heat-treated nanoporous hemin is actually comparable to that of commercial Pt/C in alkaline solution. Additionally, the carbonized nanoporous hemin is much better than commercial Pt/C in terms of durability and tolerance to methanol. This study opens up a new avenue to the production of inexpensive metalloporphyrin-based NNMEs with a high ORR performance by using a self-assembly method in combination with traditional pyrolysis. PMID:25406677

  20. A novel iron (Ⅱ) polyphthalocyanine catalyst assembled on graphene with significantly enhanced performance for oxygen reduction reaction in alkaline medium

    NASA Astrophysics Data System (ADS)

    Lin, Lin; Li, Meng; Jiang, Liqing; Li, Yongfeng; Liu, Dajun; He, Xingquan; Cui, Lili

    2014-12-01

    To realize the large-scale commercial application of direct methanol fuel cells (DMFCs), the catalysts for oxygen reduction reaction (ORR) are the crucial obstacle. Here, an efficient non-noble-metal catalyst for ORR, denoted FePPc/PSS-Gr, has been obtained by anchoring p-phenyl-bis(3,4-dicyanophenyl) ether iron(Ⅱ) polyphthalocyanine (FePPc) on poly(sodium-p-styrenesulfonate) (PSS) modified graphene (PSS-Gr) through a solvothermally assisted π-π assembling approach. The Ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) results reveal the π-π interaction between FePPc and PSS-Gr. The rotating disk electrode (RDE) and rotating ring disk electrode (RRDE) measurements show that the proposed catalyst possesses an excellent catalytic performance towards ORR comparable with the commercial Pt/C catalyst in alkaline medium, such as high onset potential (-0.08 V vs. SCE), half-wave potential (-0.19 V vs. SCE), better tolerance to methanol crossover, excellent stability (81.1%, retention after 10,000 s) and an efficient four-electron pathway. The enhanced electrocatalytic performance could be chiefly attributed to its large electrochemically accessible surface area, fast electron transfer rate of PSS-Gr, in particular, the synergistic effect between the FePPc moieties and the PSS-Gr sheets.

  1. Administration of an immunomodulatory azaspirane, SK F 105685, or human recombinant interleukin 1 stimulates myelopoiesis and enhances survival from lethal irradiation in C57Bl/6 mice

    SciTech Connect

    King, A.G.; Badger, A.M. )

    1991-08-01

    The immunomodulatory azaspirane SK F 105685 has immunosuppressive activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis. The mechanism of SK F 105685 appears to be the induction of nonspecific suppressor cell (SC) activity. SC appear to be null cells, that is, cells that lack specific cell surface markers of mature B cells, T cells, natural killer (NK) cells, or macrophages. Because the authors hypothesized that the induction of SC was associated with enhanced hematopoiesis, they sought to determine the hematopoietic potential of SK F 105685. Recombinant interleukin 1 alpha (rIL-1) was included as a positive control for hematopoietic stimulation in their studies. They demonstrate here that administration of SK F 105685 increases the number of granulocyte-macrophage colony-forming units (CFU-GM) within the bone marrow 24 h after injection in a dose-dependent manner. In addition, the percentage of CFU-GM in S-phase of the cell cycle was significantly increased, as was colony-stimulating activity (CSA) present in the serum of treated animals. In their experiments IL-1 did not increase marrow CFU-GM; however, splenic CFU-GM, the proportion of CFU-GM in S-phase of the cell cycle, and serum CSA were all increased 24 h after a single treatment. Administration of SK F 105685 24 h prior to lethal irradiation resulted in a dose-related increase in the number of surviving mice. These results demonstrate that SK F 105685 and rIL-1 stimulate myelopoiesis in vivo and suggest a mechanism by which prophylactic treatment with these agents protects mice from otherwise lethal irradiation.

  2. Soil mulching significantly enhances yields and water and nitrogen use efficiencies of maize and wheat: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Qin, Wei; Hu, Chunsheng; Oenema, Oene

    2015-11-01

    Global crop yields are limited by water and nutrient availability. Soil mulching (with plastic or straw) reduces evaporation, modifies soil temperature and thereby affects crop yields. Reported effects of mulching are sometimes contradictory, likely due to differences in climatic conditions, soil characteristics, crop species, and also water and nitrogen (N) input levels. Here we report on a meta-analysis of the effects of mulching on wheat and maize, using 1310 yield observations from 74 studies conducted in 19 countries. Our results indicate that mulching significantly increased yields, WUE (yield per unit water) and NUE (yield per unit N) by up to 60%, compared with no-mulching. Effects were larger for maize than wheat, and larger for plastic mulching than straw mulching. Interestingly, plastic mulching performed better at relatively low temperature while straw mulching showed the opposite trend. Effects of mulching also tended to decrease with increasing water input. Mulching effects were not related to soil organic matter content. In conclusion, soil mulching can significantly increase maize and wheat yields, WUE and NUE, and thereby may contribute to closing the yield gap between attainable and actual yields, especially in dryland and low nutrient input agriculture. The management of soil mulching requires site-specific knowledge.

  3. Soil mulching significantly enhances yields and water and nitrogen use efficiencies of maize and wheat: a meta-analysis

    PubMed Central

    Qin, Wei; Hu, Chunsheng; Oenema, Oene

    2015-01-01

    Global crop yields are limited by water and nutrient availability. Soil mulching (with plastic or straw) reduces evaporation, modifies soil temperature and thereby affects crop yields. Reported effects of mulching are sometimes contradictory, likely due to differences in climatic conditions, soil characteristics, crop species, and also water and nitrogen (N) input levels. Here we report on a meta-analysis of the effects of mulching on wheat and maize, using 1310 yield observations from 74 studies conducted in 19 countries. Our results indicate that mulching significantly increased yields, WUE (yield per unit water) and NUE (yield per unit N) by up to 60%, compared with no-mulching. Effects were larger for maize than wheat, and larger for plastic mulching than straw mulching. Interestingly, plastic mulching performed better at relatively low temperature while straw mulching showed the opposite trend. Effects of mulching also tended to decrease with increasing water input. Mulching effects were not related to soil organic matter content. In conclusion, soil mulching can significantly increase maize and wheat yields, WUE and NUE, and thereby may contribute to closing the yield gap between attainable and actual yields, especially in dryland and low nutrient input agriculture. The management of soil mulching requires site-specific knowledge. PMID:26586114

  4. Estimation of significant solvent concentration ranges and its application to the enhancement of the accuracy of gradient predictions.

    PubMed

    Vivó-Truyols, G; Torres-Lapasió, J R; García-Alvarez-Coque, M C

    2004-11-19

    The solvent concentration range actually useful for gradient predictions is significantly narrower than the total range scanned in a gradient run. This range, called "solvent informative range" (SIR), if known with the highest accuracy, allows to predict gradient retention times (t(g) with minimal error. The small size of the SIR supports the application of the linear solvent strength theory (LSST). Furthermore, LSST allows a closed-form solution to the integral required to predict gradient retention times, which eliminates numerical integration, needed with other retention models. A methodology that calculates the SIR by applying error analysis, and uses it to improve the accuracy in the prediction of t(g) from isocratic experiments, is proposed. The importance of those mobile-phase compositions that do not contribute significantly to the prediction of t(g) is selectively attenuated within the prediction algorithm, relying the predictions more heavily on the SIR. As a result, t(g) was found to be predicted with similar accuracy using isocratic training data with regard to predictions based on gradient training data. The approach is useful for all situations where the chromatographer is able to provide predictions of retention at constant solvent concentration, and wish to predict the retention in gradient mode. PMID:15584220

  5. Soil mulching significantly enhances yields and water and nitrogen use efficiencies of maize and wheat: a meta-analysis.

    PubMed

    Qin, Wei; Hu, Chunsheng; Oenema, Oene

    2015-01-01

    Global crop yields are limited by water and nutrient availability. Soil mulching (with plastic or straw) reduces evaporation, modifies soil temperature and thereby affects crop yields. Reported effects of mulching are sometimes contradictory, likely due to differences in climatic conditions, soil characteristics, crop species, and also water and nitrogen (N) input levels. Here we report on a meta-analysis of the effects of mulching on wheat and maize, using 1310 yield observations from 74 studies conducted in 19 countries. Our results indicate that mulching significantly increased yields, WUE (yield per unit water) and NUE (yield per unit N) by up to 60%, compared with no-mulching. Effects were larger for maize than wheat, and larger for plastic mulching than straw mulching. Interestingly, plastic mulching performed better at relatively low temperature while straw mulching showed the opposite trend. Effects of mulching also tended to decrease with increasing water input. Mulching effects were not related to soil organic matter content. In conclusion, soil mulching can significantly increase maize and wheat yields, WUE and NUE, and thereby may contribute to closing the yield gap between attainable and actual yields, especially in dryland and low nutrient input agriculture. The management of soil mulching requires site-specific knowledge. PMID:26586114

  6. Bax expression has prognostic significance that is enhanced when combined with AgNOR counts in glottic carcinomas.

    PubMed Central

    Xie, X.; Clausen, O. P.; De Angelis, P.; Boysen, M.

    1998-01-01

    Using nucleolar organizer regions (NORs) as a proliferative marker and Bax expression as a marker for apoptosis, we have studied the individual and combined prognostic significance of these markers. Successive sections of diagnostic, formalin-fixed and paraffin-embedded specimens from 69 patients with T1-4 tumours were stained with a rabbit anti-human Bax polyclonal antibody and silver nitrate for visualization of NORs (AgNORs). After classification for staining intensity and the percentage of Bax expression, a final score resulting in four classes of increasing Bax expression was obtained. AgNOR counts were expressed as mean counts (mAgNOR) and the percentage of tumour nuclei with more than one AgNOR (pAgNOR>1). Both AgNOR parameters were grouped in three classes with increasing values. Low Bax scores correlated significantly with poor prognosis (P = 0.0106). For mAgNOR and pAgNOR>1, high values correlated with poor prognosis (P = 0.0185 and P = 0.0003 respectively). A combined parameter, for which the Bax score was subtracted from the AgNOR scores, appeared to be statistically stronger than the individual parameters (P < 0.0001). Both Bax expression and AgNOR scores, and in particular the combination of these parameters, appear to be strong prognostic markers in glottic squamous cell carcinomas. PMID:9662258

  7. Positive Modulation of GABAB Receptors Decreased Nicotine Self-administration and Counteracted Nicotine-induced Enhancement of Brain Reward Function in Rats

    PubMed Central

    Paterson, Neil E.; Vlachou, Styliani; Guery, Sebastien; Kaupmann, Klemens; Froestl, Wolfgang; Markou, Athina

    2008-01-01

    Acute administration of γ-aminobutyric acid (GABA)-B receptor agonists decreases nicotine, cocaine, ethanol, and heroin self-administration, and also decreases food-maintained responding and suppresses locomotor activity at high doses. GABAB receptor positive modulators may represent potentially improved therapeutic compounds because of their fewer side-effects than receptor agonists. The present study investigated the effects of administration of the GABAB receptor positive modulators 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177), and co-administration of the GABAB receptor positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) with the GABAB receptor agonist (3-amino-2[S]-hydroxypropyl)-methylphosphinic acid (CGP44532) on nicotine- and food-maintained responding under fixed-ratio 5 (FR5) and progressive-ratio schedules of reinforcement. Furthermore, the effects of BHF177 and CGP44532 on nicotine-induced enhancement of brain reward function were evaluated. The results indicated that administration of CGP7930 decreased nicotine self-administration under an FR5 schedule. Administration of either GS39783 or CGP44532 selectively decreased nicotine self-administration, while co-administration of these compounds had additive effects. BHF177 administration selectively decreased nicotine-, but not food-, maintained responding under FR5 and progressive-ratio schedules. The nicotine-induced enhancement of brain reward function was blocked by BHF177 or CGP44532, although the highest doses of both compounds, particularly CGP44532, decreased brain reward function when administered alone, suggesting an additive, rather than interactive, effect. Overall, the present results indicate that GABAB receptor positive modulators, similarly to GABAB receptor agonists, attenuated the reinforcing and reward-enhancing

  8. Adult acclimation to combined temperature and pH stressors significantly enhances reproductive outcomes compared to short-term exposures.

    PubMed

    Suckling, Coleen C; Clark, Melody S; Richard, Joelle; Morley, Simon A; Thorne, Michael A S; Harper, Elizabeth M; Peck, Lloyd S

    2015-05-01

    This study examined the effects of long-term culture under altered conditions on the Antarctic sea urchin, Sterechinus neumayeri. Sterechinus neumayeri was cultured under the combined environmental stressors of lowered pH (-0.3 and -0.5 pH units) and increased temperature (+2 °C) for 2 years. This time-scale covered two full reproductive cycles in this species and analyses included studies on both adult metabolism and larval development. Adults took at least 6-8 months to acclimate to the altered conditions, but beyond this, there was no detectable effect of temperature or pH. Animals were spawned after 6 and 17 months exposure to altered conditions, with markedly different outcomes. At 6 months, the percentage hatching and larval survival rates were greatest in the animals kept at 0 °C under current pH conditions, whilst those under lowered pH and +2 °C performed significantly less well. After 17 months, performance was not significantly different across treatments, including controls. However, under the altered conditions urchins produced larger eggs compared with control animals. These data show that under long-term culture adult S. neumayeri appear to acclimate their metabolic and reproductive physiology to the combined stressors of altered pH and increased temperature, with relatively little measureable effect. They also emphasize the importance of long-term studies in evaluating effects of altered pH, particularly in slow developing marine species with long gonad maturation times, as the effects of altered conditions cannot be accurately evaluated unless gonads have fully matured under the new conditions. PMID:25491898

  9. Dietary Administration of Lactobacillus plantarum Enhanced Growth Performance and Innate Immune Response of Siberian Sturgeon, Acipenser baerii.

    PubMed

    Pourgholam, Moheb Ali; Khara, Hossein; Safari, Reza; Sadati, Mohammad Ali Yazdani; Aramli, Mohammad Sadegh

    2016-03-01

    We investigated the effects of Lactobacillus plantarum used as a dietary supplement on the growth performance and innate immune response in juvenile Siberian sturgeon Acipenser baerii. Juvenile fish (14.6 ± 2.3 g) were fed three experimental diets prepared by supplementing a basal diet with L. plantarum at different concentrations [1 × 10(7), 1 × 10(8) and 1 × 10(9) colony-forming units (cfu) g(-1)] and a control (non-supplemented basal) diet for 8 weeks. Growth performance indices were increased in fish fed the 1 × 10(8) cfu g(-1) L. plantarum diet compared to the other groups. There was an increased innate immune response in fish fed the experimental diets. The highest levels of lysozyme activity, total immunoglobulin (IgM) and complement component 3 (C3) were observed in fish fed the diet containing L. plantarum at a concentration of 1 × 10(8) cfu g(-1), but there was no significant difference in the level of complement component 4 (C4) in fish fed the experimental diets or the control diet. The present study underlying some positive effects (growth performance and immune indices) of dietary administration of L. plantarum at a concentration of 1 × 10(8) cfu g(-1) in the Siberian sturgeon. PMID:26686864

  10. Significant School Law Cases Pending Before the U.S. Supreme Court. What Do They Portend for the Governance and Administration of the Public Schools?

    ERIC Educational Resources Information Center

    Shannon, Thomas A.

    Civil rights is the central theme of the cases affecting public school governance that the U.S. Supreme Court has agreed to hear this term. This paper discusses those cases in detail. It also notes that the cases the court refuses to hear have as significant an impact on school district governance as those cases it actually hears. School law cases…

  11. Enhancement of antidepressant-like activity by joint administration of imipramine and magnesium in the forced swim test: Behavioral and pharmacokinetic studies in mice.

    PubMed

    Poleszak, Ewa; Wlaź, Piotr; Szewczyk, Bernadeta; Kedzierska, Ewa; Wyska, Elzbieta; Librowski, Tadeusz; Szymura-Oleksiak, Joanna; Fidecka, Sylwia; Pilc, Andrzej; Nowak, Gabriel

    2005-07-01

    The effect of joint administration of imipramine (IMI) and magnesium (Mg) on antidepressant-like activity was studied in mice using forced swim test (FST). Mg doses ineffective per se (5 and 10 mg/kg) given jointly with IMI also at ineffective doses (10 and 15 mg/kg) resulted in a potent reduction in the immobility time. Since these combined treatments did not influence locomotor activity, the antidepressant-like activity was not due to non-specific behavioral activation. Moreover, we estimated the effect of joint administration of magnesium and IMI in FST on serum and brain magnesium, IMI and its active metabolite desipramine (DMI) concentrations in mice. Swim stress (mice subjected to FST) increased the magnesium concentration in serum and decreased it in the brain compared to naive animals. Moreover administration of IMI increased (normalized) magnesium brain concentration, without influence on the serum level. Joint administration of IMI and magnesium did not influence magnesium (compared with FST) or IMI and DMI (compared with IMI treatment alone) concentrations in both examined tissues. The present data demonstrated an enhancement of the antidepressant-like effect by joint administration of IMI and magnesium in the FST, and further indicate the particular role of magnesium in the antidepressant action. Since there was no increase in IMI, DMI or magnesium concentration after joint administration of magnesium and IMI, the data suggest that pharmacodynamic rather than pharmacokinetic interaction between magnesium and IMI is accountable for behavioral effect in the FST. PMID:15936065

  12. [Enhancement of the phagocytic activity of cells of the mononuclear phagocytosing system by the peroral administration of lactobacilli].

    PubMed

    Zaĭtseva, L G; Gorskaia, E M; Lentsner, A A; Shustrova, N M

    1986-09-01

    The phagocytic function of the peritoneal exudate cells after oral and intraperitoneal administration of Lactobacillus casei subsp. casei, L. plantarum and L. fermentum was studied on mice C57Bl and inbred rats CDF/F344/Crl. The phagocytic function was estimated by the capacity for absorbing and excreting 14C-labeled typhoid vaccine. Intraperitoneal administration of a mixture of various Lactobacillus strains resulted in two-fold increase of the bacteria absorption and digestion when the Lactobacillus strains were administered 4 days before administration of the test antigen. On their simultaneous administration the phagocytic function of the peritoneal exudate cells lowered. Oral administration of the Lactobacillus strains for 6 and 18 days resulted, respectively, in 1.5- and 3-fold increase of absorption and digestion of the labeled typhoid vaccine. This route of Lactobacillus administration provided more rapid increase of the level of the antibodies to the typhoid antigen. Possible immunomodulating action of Lactobacillus administered orally is discussed. PMID:3777898

  13. Noisy galvanic vestibular stimulation enhances spatial memory in cognitive impairment-induced by intracerebroventricular-streptozotocin administration.

    PubMed

    Adel Ghahraman, Mansoureh; Zahmatkesh, Maryam; Pourbakht, Akram; Seifi, Behjat; Jalaie, Shohreh; Adeli, Soheila; Niknami, Zohreh

    2016-04-01

    There are several anatomical connections between vestibular system and brain areas construct spatial memory. Since subliminal noisy galvanic vestibular stimulation (GVS) has been demonstrated to enhance some types of memory, we speculated that application of noisy GVS may improve spatial memory in a rat model of intracerebroventricular streptozotocin (ICV-STZ)-induced cognitive impairment. Moreover, we attempted to determine the effect of repeated exposure to GVS on spatial memory performance. The spatial memory was assessed using Morris water maze test. The groups received 1 (ICV-STZ/GVS-I) or 5 (ICV-STZ/GVS-II) sessions, each lasting 30 min, of low amplitude noisy GVS, or no GVS at all (Control, ICV-saline, ICV-STZ/noGVS). Hippocampal morphological changes investigated with cresyl violet staining and the immediate early gene product c-Fos, as a neuronal activity marker, was measured. Hippocampal c-Fos positive cells increased in both GVS stimulated groups. We observed significantly improved spatial performance only in ICV-STZ/GVS-II group. Histological evaluation showed normal density in ICV-STZ/GVS-II group whereas degeneration observed in ICV-STZ/GVS-I group similar to ICV-STZ/noGVS. The results showed the improvement of memory impairment after repeated exposure to GVS. This effect may be due in part to frequent activation of the vestibular neurons and the hippocampal regions connected to them. Our current study suggests the potential role of GVS as a practical method to combat cognitive decline induced by sporadic Alzheimer disease. PMID:26892259

  14. Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

    PubMed

    Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

    2011-12-15

    Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

  15. Administrative Effectiveness in Higher Education.

    ERIC Educational Resources Information Center

    Whetten, David A.; Cameron, Kim S.

    1985-01-01

    Determinants of organizational and administrative effectiveness in higher education are discussed, and eight administrator characteristics associated with maintaining and enhancing institutional effectiveness are identified. (MSE)

  16. Augmented behavioral response and enhanced synaptosomal calcium transport induced by repeated cocaine administration are decreased by calcium channel blockers

    PubMed Central

    Mills, K.; Ansah, T.A.; Ali, S.F.; Mukherjee, S.; Shockley, D.C.

    2009-01-01

    Recent studies suggest that calcium influx via L-type calcium channels is necessary for psychostimulant-induced behavioral sensitization. In addition, chronic amphetamine upregulates subtype Cav1.2-containing L-type calcium channels. In the present studies, we assessed the effect of calcium channel blockers (CCBs) on cocaine-induced behavioral sentitization and determined whether the functional activity of L-type calcium channels is altered after repeated cocaine administration. Rats were administered daily intraperitoneal injections of either flunarizine (40 mg/kg), diltiazem (40 mg/kg) or cocaine (20 mg/kg) and the combination of the CCB’s and cocaine for 30 days. Motor activities were monitored on Day 1, and every 6th day during the 30-day treatment period. Daily cocaine administration produced increased locomotor activity. Maximal augmentation of behavioral response to repeated cocaine administration was observed on Day 18. Flunarizine pretreatment abolished the augmented behavioral response to repeated cocaine administration while diltiazem was less effective. Measurement of tissue monoamine levels on Day 18 revealed cocaine-induced increases in DA and 5-HT in the nucleus accumbens. By contrast to behavioral response, diltiazem was more effective in attenuating increases in monoamine levels than flunarizine. Cocaine administration for 18 days produced increases in calcium-uptake in synaptosomes prepared from the nucleus accumbens and frontal cortex. Increases in calcium-uptake were abolished by flunarizine- and diltiazem-pretreatment. Taken together, the augmented cocaine-induced behavioral response on Day 18 may be due to increased calcium uptake in the nucleus accumbens leading to increased dopamine (DA) and serotonin (5-HT) release. Flunarizine and diltiazem attenuated the behavioral response by decreasing calcium uptake and decreasing neurochemical release. PMID:17689567

  17. Gr-1+CD11b+ myeloid cells efficiently home to site of injury after intravenous administration and enhance diabetic wound healing by neoangiogenesis

    PubMed Central

    Tong, Xiaozhe; Lv, Gang; Huang, Jianhua; Min, Yongfen; Yang, Li; Lin, Pengnian Charles

    2014-01-01

    Vascularization is an important factor that affects diabetic wound healing. There is increasing evidence that myeloid cell lineages play a role in neovascularization. In this study, the efficiency of Gr-1+CD11b+ myeloid cells to home to the site of injury and enhance diabetic wound healing by neoangiogenesis after intravenous administration was investigated. Gr-1+CD11b+ myeloid cells were injected into tail vein after establishment of dorsal window chamber, hindlimb ischaemia and ear-punch injury in diabetic or non-diabetic mice. The Gr-1+CD11b+ myeloid cells efficiently homed to the site of injury after intravenous administration and increased neoangiogenesis. The chemokine receptor type 4 (CXCR4) is robustly expressed by Gr-1+CD11b+ myeloid cells. Inhibition of CXCR4 decreases the homing ability of Gr-1+CD11b+ myeloid cells to the site of injury, which indicates that the CXCR4/SDF-1 axis plays an important role in the homing of Gr-1+CD11b+ myeloid cells to the site of injury. In addition, Gr-1+CD11b+ myeloid cells were found to improve blood flow recovery of ischaemic limb and enhance wound healing in diabetic mice by neoangiogenesis after intravenous administration. Taken together, the results of this study suggest that Gr-1+CD11b+ myeloid cells may serve as a potential cell therapy for diabetic wound healing. PMID:24645717

  18. Significant enhancement in thermoelectric properties of polycrystalline Pr-doped SrTiO{sub 3−δ} ceramics originating from nonuniform distribution of Pr dopants

    SciTech Connect

    Dehkordi, Arash Mehdizadeh; Bhattacharya, Sriparna; He, Jian; Alshareef, Husam N.; Tritt, Terry M.

    2014-05-12

    Recently, we have reported a significant enhancement (>70% at 500 °C) in the thermoelectric power factor (PF) of bulk polycrystalline Pr-doped SrTiO{sub 3} ceramics employing a novel synthesis strategy which led to the highest ever reported values of PF among doped polycrystalline SrTiO{sub 3}. It was found that the formation of Pr-rich grain boundary regions gives rise to an enhancement in carrier mobility. In this Letter, we investigate the electronic and thermal transport in Sr{sub 1−x}Pr{sub x}TiO{sub 3} ceramics in order to determine the optimum doping concentration and to evaluate the overall thermoelectric performance. Simultaneous enhancement in the thermoelectric power factor and reduction in thermal conductivity in these samples resulted in more than 30% improvement in the dimensionless thermoelectric figure of merit (ZT) for the whole temperature range over all previously reported maximum values. Maximum ZT value of 0.35 was obtained at 500 °C.

  19. Significantly enhanced ferroelectricity and magnetic properties in (Sr0.5Ca0.5)TiO3-modified BiFeO3 ceramics

    NASA Astrophysics Data System (ADS)

    Liu, Juan; Liu, Xiao Qiang; Chen, Xiang Ming

    2015-05-01

    BiFeO3 multiferroic ceramics were modified by introducing (Sr0.5Ca0.5)TiO3 to form solid solutions. The single phase structure was easy to be obtained in Bi1-x(Sr0.5Ca0.5)xFe1-xTixO3 (x = 0.2, 0.25, 0.3, and 0.4) solid solutions. Rietveld refinement of X-ray diffraction data revealed a transition from rhombohedral R3c (x = 0.2, 0.25, and 0.3) to orthorhombic Pnma (x = 0.4). Current density-field (J-E) characteristics indicated that the leakage current density was reduced by three orders of magnitude in Bi1-x(Sr0.5Ca0.5)xFe1-xTixO3 ceramics. Both the ferroelectricity and magnetic properties were significantly enhanced in the present solid solutions. P-E hysteresis loop measurements with dynamic leakage current compensation methods showed the significantly enhanced ferroelectric properties for x = 0.25 and 0.3 and the paraelectric behavior for x = 0.4. The best ferromagnetic characteristics were achieved in the composition of x = 0.25, where the saturated M-H loop was determined with Mr = 34.8 emu/mol. The improvement of ferroelectricity was mainly due to the suppressed leakage current, and the enhanced magnetism originated from the partial substitution of Fe3+ by Ti4+, which destroyed its previous spiral structure to allow the appearance of a macroscopic magnetization.

  20. Significant enhancement in the photocatalytic activity of N, W co-doped TiO2 nanomaterials for promising environmental applications.

    PubMed

    Thind, Sapanbir S; Wu, Guosheng; Tian, Min; Chen, Aicheng

    2012-11-30

    In this work, a mesoporous N, W co-doped TiO(2) photocatalyst was synthesized via a one-step solution combustion method, which utilized urea as the nitrogen source and sodium tungstate as the tungsten source. The photocatalytic activity of the N, W co-doped TiO(2) photocatalyst was significantly enhanced by a facile UV pretreatment approach and was evaluated by measuring the rate of photodegradation of Rhodamine B under both UV and visible (λ > 420) light. Following the UV pretreatment, the UV photocatalytic activity of the N, W co-doped TiO(2) was doubled. In terms of visible light activity, the UV pretreatment resulted in an extraordinary >12 fold improvement. In order to gain insight into this substantial enhancement, the N, W co-doped TiO(2) photocatalysts were studied using x-ray diffraction, transmission electron microscopy, N(2) physisorption, UV-vis absorbance spectroscopy and x-ray photoelectron spectroscopy prior to and following the UV pretreatment. Our experimental results have revealed that this significant augmentation of photocatalytic activity may be attributed to several synergetic factors, including increase of the specific surface area, reduction of the band gap energy and the removal of carbon impurities. PMID:23110785

  1. Significant enhancements of nitrogen oxides, black carbon, and ozone in the North Atlantic lower free troposphere resulting from North American boreal wildfires

    NASA Astrophysics Data System (ADS)

    Val MartíN, M.; Honrath, R. E.; Owen, R. C.; Pfister, G.; Fialho, P.; Barata, F.

    2006-12-01

    Extensive wildfires burned in northern North America during summer 2004, releasing large amounts of trace gases and aerosols into the atmosphere. Emissions from these wildfires frequently impacted the PICO-NARE station, a mountaintop site situated 6-15 days downwind from the fires in the Azores Islands. To assess the impacts of the boreal wildfire emissions on the levels of aerosol black carbon (BC), nitrogen oxides and O3 downwind from North America, we analyzed measurements of CO, BC, total reactive nitrogen oxides (NOy), NOx (NO + NO2) and O3 made from June to September 2004 in combination with MOZART chemical transport model simulations. Long-range transport of boreal wildfire emissions resulted in large enhancements of CO, BC, NOy and NOx, with levels up to 250 ppbv, 665 ng m-3, 1100 pptv and 135 pptv, respectively. Enhancement ratios relative to CO were variable in the plumes sampled, most likely because of variations in wildfire emissions and removal processes during transport. Analyses of ΔBC/ΔCO, ΔNOy/ΔCO and ΔNOx/ΔCO ratios indicate that NOy and BC were on average efficiently exported in these plumes and suggest that decomposition of PAN to NOx was a significant source of NOx. High levels of NOx suggest continuing formation of O3 in these well-aged plumes. O3 levels were also significantly enhanced in the plumes, reaching up to 75 ppbv. Analysis of ΔO3/ΔCO ratios showed distinct behaviors of O3 in the plumes, which varied from significant to lower O3 production. We identify several potential reasons for the complex effects of boreal wildfire emissions on O3 and conclude that this behavior needs to be explored further in the future. These observations demonstrate that boreal wildfire emissions significantly contributed to the NOx and O3 budgets in the central North Atlantic lower free troposphere during summer 2004 and imply large-scale impacts on direct radiative forcing of the atmosphere and on tropospheric NOx and O3.

  2. Powerful Complex Immunoadjuvant Based on Synergistic Effect of Combined TLR4 and NOD2 Activation Significantly Enhances Magnitude of Humoral and Cellular Adaptive Immune Responses

    PubMed Central

    Dzharullaeva, Alina S.; Tukhvatulina, Natalia M.; Shcheblyakov, Dmitry V.; Shmarov, Maxim M.; Dolzhikova, Inna V.; Stanhope-Baker, Patricia; Naroditsky, Boris S.; Gudkov, Andrei V.; Logunov, Denis Y.; Gintsburg, Alexander L.

    2016-01-01

    Binding of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) activates innate immune responses and contributes to development of adaptive immunity. Simultaneous stimulation of different types of PRRs can have synergistic immunostimulatory effects resulting in enhanced production of molecules that mediate innate immunity such as inflammatory cytokines, antimicrobial peptides, etc. Here, we evaluated the impact of combined stimulation of PRRs from different families on adaptive immunity by generating alum-based vaccine formulations with ovalbumin as a model antigen and the Toll-like receptor 4 (TLR4) agonist MPLA and the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist MDP adsorbed individually or together on the alum-ovalbumin particles. Multiple in vitro and in vivo readouts of immune system activation all showed that while individual PRR agonists increased the immunogenicity of vaccines compared to alum alone, the combination of both PRR agonists was significantly more effective. Combined stimulation of TLR4 and NOD2 results in a stronger and broader transcriptional response in THP-1 cells compared to individual PRR stimulation. Immunostimulatory composition containing both PRR agonists (MPLA and MDP) in the context of the alum-based ovalbumin vaccine also enhanced uptake of vaccine particles by bone marrow derived dendritic cells (BMDCs) and promoted maturation (up-regulation of expression of CD80, CD86, MHCII) and activation (production of cytokines) of BMDCs. Finally, immunization of mice with vaccine particles containing both PRR agonists resulted in enhanced cellular immunity as indicated by increased proliferation and activation (IFN-γ production) of splenic CD4+ and CD8+ T cells following in vitro restimulation with ovalbumin and enhanced humoral immunity as indicated by higher titers of ovalbumin-specific IgG antibodies. These results indicate that combined stimulation of TLR4 and NOD2

  3. Achieving significantly enhanced visible-light photocatalytic efficiency using a polyelectrolyte: the composites of exfoliated titania nanosheets, graphene, and poly(diallyl-dimethyl-ammonium chloride)

    NASA Astrophysics Data System (ADS)

    Zhang, Qian; An, Qi; Luan, Xinglong; Huang, Hongwei; Li, Xiaowei; Meng, Zilin; Tong, Wangshu; Chen, Xiaodong; Chu, Paul K.; Zhang, Yihe

    2015-08-01

    A high-performance visible-light-active photocatalyst is prepared using the polyelectrolyte/exfoliated titania nanosheet/graphene oxide (GO) precursor by flocculation followed by calcination. The polyelectrolyte poly(diallyl-dimethyl-ammonium chloride) serves not only as an effective binder to precipitate GO and titania nanosheets, but also boosts the overall performance of the catalyst significantly. Unlike most titania nanosheet-based catalysts reported in the literature, the composite absorbs light in the UV-Vis-NIR range. Its decomposition rate of methylene blue is 98% under visible light. This novel strategy of using a polymer to enhance the catalytic performance of titania nanosheet-based catalysts affords immense potential in designing and fabricating next-generation photocatalysts with high efficiency.A high-performance visible-light-active photocatalyst is prepared using the polyelectrolyte/exfoliated titania nanosheet/graphene oxide (GO) precursor by flocculation followed by calcination. The polyelectrolyte poly(diallyl-dimethyl-ammonium chloride) serves not only as an effective binder to precipitate GO and titania nanosheets, but also boosts the overall performance of the catalyst significantly. Unlike most titania nanosheet-based catalysts reported in the literature, the composite absorbs light in the UV-Vis-NIR range. Its decomposition rate of methylene blue is 98% under visible light. This novel strategy of using a polymer to enhance the catalytic performance of titania nanosheet-based catalysts affords immense potential in designing and fabricating next-generation photocatalysts with high efficiency. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03256c

  4. Enhancement of 4-biphenylacetic acid bioavailability in rats by its beta-cyclodextrin complex after oral administration.

    PubMed

    Puglisi, G; Santagati, N A; Ventura, C A; Pignatello, R; Panico, A M; Spampinato, S

    1991-06-01

    4-Biphenylacetic acid, a potent non-steroidal anti-inflammatory agent forms a solid inclusion complex with beta-cyclodextrin in a 1:1 molar ratio, which exhibits better solubility and dissolution characteristics than the uncomplexed drug. Following oral administration of the complex to rats, quicker and higher drug plasma concentrations can be achieved than with the drug alone. Parallel studies, using the carrageenan paw oedema test, demonstrate a greater anti-inflammatory activity of the complex (ED50 of 2.9 mg kg-1 for the complex and of 6.2 mg kg-1 for the free drug). The complex displayed a better gastric tolerability in the rat than drug alone. PMID:1681057

  5. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

    PubMed

    Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

    2009-01-01

    Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug. PMID:18418357

  6. Antiproliferative effects of anastrozole on MCF-7 human breast cancer cells in vitro are significantly enhanced by combined treatment with testosterone undecanoate.

    PubMed

    Chen, Rong; Cui, Junwei; Wang, Qinqin; Li, Peng; Liu, Xiaoling; Hu, Hui; Wei, Wei

    2015-07-01

    The present study aimed to assess the effects of aromatase inhibitor anastrozole and testosterone undecanoate, separately and in combination, on proliferation and apoptosis in MCF-7 human breast cancer cells cultured in vitro. The effects of various concentrations of these drugs on the proliferation of MCF-7 cells were evaluated by CCK8 assay, the levels of cell apoptosis were evaluated by flow cytometry with Annexin-V/propidium iodide staining and androgen receptor (AR) protein expression was determined by western blot analysis. The results of the CCK8 assay indicated that greater antiproliferative activity was detected in the MCF-7 cells in the combined treatment groups, compared with those treated with anastrozole or testosterone undecanoate alone. Flow cytometric analysis of apoptosis revealed that treatment with a combination of the two drugs generated a higher percentage of apoptotic cells, particularly when the two drugs were applied for 48 h, compared with single drug treatment. Western blot analysis revealed a significant decrease in AR protein expression in the combined treatment groups compared with MCF7 cells treated with single drugs. The results of the present study provided evidence supporting the potential of a combination of anastrozole and testosterone undecanoate as a novel therapeutic strategy for the treatment of breast cancer. Furthermore, it was demonstrated that the antiproliferative effects of anastrozole were significantly enhanced by combined treatment with testosterone undecanoate via the AR signaling pathway. PMID:25738971

  7. Significant performance enhancement of yttrium-doped barium cerate proton conductor as electrolyte for solid oxide fuel cells through a Pd ingress-egress approach

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Ran, Ran; Li, Sidian; Jiao, Yong; Tade, Moses O.; Shao, Zongping

    2014-07-01

    Proton-conducting perovskite oxides are excellent electrolyte materials for SOFCs that may improve power density at reduced temperatures and increase fuel efficiency, thus encouraging the widespread implementation of this attractive technology. The main challenges in the application of these oxides in SOFCs are difficult sintering and insufficient conductivity in real cells. In this study, we propose a novel method to significantly enhance the performance of a yttrium-doped barium cerate proton conductor as an electrolyte for SOFCs through a Pd ingress-egress approach to the development of BaCe0.8Y0.1Pd0.1O3-δ (BCYP10). The capability of the Pd egress from the BCYP10 perovskite lattice is demonstrated by H2-TPR, XRD, EDX mapping of STEM and XPS. Significant improvement in the sinterability is observed after the introduction of Pd due to the increased ionic conductivity and the sintering aid effect of egressed Pd. The formation of a B-site cation defect structure after Pd egress and the consequent modification of perovskite grain boundaries with Pd nanoparticles leads to a proton conductivity of BCYP10 that is approximately 3 times higher than that of BCY under a reducing atmosphere. A single cell with a thin film BCYP10 electrolyte reaches a peak power density as high as 645 mA cm-2 at 700 °C.

  8. The development of orally administrable gemcitabine prodrugs with D-enantiomer amino acids: Enhanced membrane permeability and enzymatic stability

    PubMed Central

    Tsume, Yasuhiro; Incecayir, Tuba; Song, Xueqin; Hilfinger, John M.; Amidon, Gordon L.

    2014-01-01

    Gemcitabine prodrugs with D- and L-configuration amino acids were synthesized and their chemical stability in buffers, resistance to glycosidic bond metabolism, enzymatic activation, permeability in Caco-2 cells and mouse intestinal membrane, anti-proliferation activity in cancer cell were determined and compared to that of parent drug, gemcitabine. Prodrugs containing D-configuration amino acids were enzymatically more stable than ones with L-configuration amino acids. The activation of all gemcitabine prodrugs was 1.3–17.6-fold faster in cancer cell homogenate than their hydrolysis in buffer, suggesting enzymatic action. The enzymatic activation of amino acid monoester prodrugs containing D-configuration amino acids in cell homogenates was 2.2–10.9-fold slower than one of amino acid monoester prodrugs with L-configuration amino acids. All prodrugs exhibited enhanced resistance to glycosidic bond metabolism by thymidine phosphorylase compared to parent gemcitabine. Gemcitabine prodrugs showed superior the effective permeability in mouse jejunum to gemcitabine. More importantly, the high plasma concentration of D-amino acid gemcitabine prodrugs was observed more than one of L-amino acid gem-citabine prodrugs. In general, the 5′-mono-amino acid monoester gemcitabine prodrugs exhibited higher permeability and uptake than their parent drug, gemcitabine. Cell proliferation assays in AsPC-1 pancreatic ductal cell line indicated that gemcitabine prodrugs were more potent than their parent drug, gemcitabine. The transport and enzymatic profiles of 5′-D-valyl-gemcitabine and 5′-D-phenylalanyl-gem-citabine suggest their potential for increased oral uptake and delayed enzymatic bioconversion as well as enhanced uptake and cytotoxic activity in cancer cells, would facilitate the development of oral dosage form for anti-cancer agents and, hence, improve the quality of life for the cancer patients. PMID:24361461

  9. Medical students' participation in the 2009 Novel H1N1 influenza vaccination administration: policy alternatives for effective student utilization to enhance surge capacity in disasters.

    PubMed

    Kaiser, Heather E; Barnett, Daniel J; Hayanga, Awori J; Brown, Meghan E; Filak, Andrew T

    2011-06-01

    As cases of 2009 novel H1N1 influenza became prevalent in Cincinnati, Ohio, Hamilton County Public Health called upon the University of Cincinnati College of Medicine to enhance its surge capacity in vaccination administration. Although the collaboration was well organized, it became evident that a system should exist for medical students' involvement in disaster response and recovery efforts in advance of a disaster. Therefore, 5 policy alternatives for effective utilization of medical students in disaster-response efforts have been examined: maintaining the status quo, enhancing the Medical Reserve Corps, creating medical school-based disaster-response units, using students within another selected disaster-response organization, or devising an entirely new plan for medical students' utilization. The intent of presenting these policy alternatives is to foster a policy dialogue around creating a more formalized approach for integrating medical students into disaster surge capacity-enhancement strategies. Using medical students to supplement the current and future workforce may help substantially in achieving goals related to workforce requirements. Discussions will be necessary to translate policy into practice. PMID:21482704

  10. Administration of a DPP-IV Inhibitor Enhances the Intestinal Adaptation in a Mouse Model of Short Bowel Syndrome

    PubMed Central

    Okawada, Manabu; Holst, Jens J.; Teitelbaum, Daniel H.

    2011-01-01

    Background Glucagon-like peptide-2(GLP-2) induces small intestine mucosal epithelial cell (EC) proliferation; and may have benefit for patients suffering from short bowel syndrome (SBS). However, GLP-2 is rapidly inactivated in vivo by dipeptidyl peptidase IV (DPPIV). Therefore, we hypothesized that selectively inhibiting DPPIV would prolong the circulating life of GLP-2 and lead to increased intestinal adaptation after development of SBS. Methods 8-week old C57BL/6J mice underwent a 50% proximal small bowel resection and were treated with either sitagliptin, a DPPIV-inhibitor (DPPIV-I), starting 1 day before surgery versus placebo. DPPIV-I efficacy was assessed 3 days after resection, including intestinal morphology, EC apoptosis and EC proliferation. Adaptive mechanisms were assessed with quantitative real-time PCR, and plasma bioactive GLP-2 was measured by radioimmunoassay. RESULT Body weight loss and peripheral blood glucose levels did not change compared to SBS controls. DPPIV-I treatment led to significant increases in villus height and crypt depth. DPPIV-I treatment did not significantly change EC apoptosis rates, but significantly increased crypt EC proliferation versus placebo-SBS controls. DPPIV-I treatment markedly increased mRNA expression of β-catenin and c-myc in ileal mucosa. Plasma GLP-2 levels significantly increased(~40.9%) in DPPIV-I-SBS mice. Conclusions DPPIV- I treatment increased SBS adaptation, and may potentially be useful for SBS patients. PMID:21719060

  11. Wheat Germ Agglutinin Enhanced Cerebral Uptake of Anti-Aß Antibody after Intranasal Administration in 5XFAD Mice

    PubMed Central

    Chauhan, Neelima B.; Davis, Francesca; Chun, Xiao

    2011-01-01

    Alzheimer's disease (AD) is the 6th leading cause of death in United States afflicting >5 million Americans. This number is estimated to triple by the middle of the century if effective treatments are not discovered. Current therapy for AD is mainly symptomatic. Effective disease-modifying treatments are needed that would eliminate the cause rather than the symptoms of the disease. Polymerization of monomeric beta-amyloid peptide (Aß) into dimers, soluble oligomers and insoluble fibrils is considered the prime causative factor in triggering AD pathogenesis. Based on these facts, removal/reduction of Aß has gained importance as a primary therapeutic target in treating the cause of the disease. In that regard, passive immunotherapy with direct delivery of anti-Aß antibodies to the brain has shown great promise, but awaits the challenge of overcoming greater influx of anti-Aß antibody into the brain. This investigation was undertaken to maximize direct delivery of immunotherapeutics to the brain by using Wheat Germ Agglutinin (WGA) as a novel axonal transporter-carrier to be conjugated with anti-Aß antibody (6E10) raised against EFRHDS 3-8 amino acid (aa) epitopes of Aß known to react with 1-16 aa residues of mono-/di-/oligomeric Aß. This is the first report showing the use of WGA as an efficient axonal transporter carrier that not only enhanced the influx of anti-Aß antibody directly into the brain but also resulted in greater reduction of cerebral Aß compared to the unconjugated anti-Aß antibody delivered intranasally in Alzheimer's 5XFAD model. PMID:21840361

  12. The National Aeronautics and Space Administration-U.S. Public Health Service Health Evaluation and Enhancement Program - Summary of results.

    NASA Technical Reports Server (NTRS)

    Durbeck, D. C.; Heinzelmann, F.; Schacter, J.; Haskell, W. L.; Payne, G. H.; Moxley, R. T., III; Nemiroff, M.; Limoncelli, D. D.; Arnoldi, L. B.; Fox, S. M., III

    1972-01-01

    An exercise program was initiated in a federal agency to assess the feasibility of such a program, and to identify the factors that influenced joining, adherence to, and effectiveness of the program. The program was utilized by 237 of the 998 eligible federal employees; mean attendance rate was 1.3 days/week. Those who volunteered perceived a need for increased physical activity, believed they had sufficient time to participate and derived subjective as well as objective benefits. Significant improvements were found in heart rate response to the standard exercise test, body weight, skinfold measurements and triglyceride levels.

  13. Water in the hydration shell of halide ions has significantly reduced Fermi resonance and moderately enhanced Raman cross section in the OH stretch regions.

    PubMed

    Ahmed, Mohammed; Singh, Ajay K; Mondal, Jahur A; Sarkar, Sisir K

    2013-08-22

    Water in the presence of electrolytes plays an important role in biological and industrial processes. The properties of water, such as the intermolecular coupling, Fermi resonance (FR), hydrogen-bonding, and Raman cross section were investigated by measuring the Raman spectra in the OD and OH stretch regions in presence of alkali halides (NaX; X = F, Cl, Br, I). It is observed that the changes in spectral characteristics by the addition of NaX in D2O are similar to those obtained by the addition of H2O in D2O. The spectral width decreases significantly by the addition of NaX in D2O (H2O) than that in the isotopically diluted water. Quantitative estimation, on the basis of integrated Raman intensity, revealed that the relative Raman cross section, σ(H)/σ(b) (σ(H) and σ(b) are the average Raman cross section of water in the first hydration shell of X(-) and in bulk, respectively), in D2O and H2O is higher than those in the respective isotopically diluted water. These results suggest that water in the hydration shell has reduced FR and intermolecular coupling compared to those in bulk. In the isotopically diluted water, the relative Raman cross section increases with increase in size of the halide ions (σ(H)/σ(b) = 0.6, 1.1, 1.5, and 1.9 for F(-), Cl(-), Br(-), and I(-), respectively), which is assignable to the enhancement of Raman cross section by charge transfer from halide ions to the hydrating water. Nevertheless, the experimentally determined σ(H)/σ(b) is lower than the calculated values obtained on the basis of the energy of the charge transfer state of water. The weak enhancement of σ(H)/σ(b) signifies that the charge transfer transition in the hydration shell of halide ions causes little change in the OD (OH) bond lengths of hydrating water. PMID:23895453

  14. Cholestyramine-enhanced fecal elimination of carbon-14 in rats after administration of ammonium (/sup 14/C)perfluorooctanoate or potassium (/sup 14/C)perfluorooctanesulfonate

    SciTech Connect

    Johnson, J.D.; Gibson, S.J.; Ober, R.E.

    1984-12-01

    After a single intravenous dose of ammonium (/sup 14/C)perfluorooctanoate (( /sup 14/C)PFO, 13.3 mg/kg) or of potassium (/sup 14/C)perfluorooctanesulfonate (( /sup 14/C)PFOS, 3.4 mg/kg) to rats, cholestyramine fed daily as a 4% mixture in feed was shown to increase the total carbon-14 eliminated via feces and to decrease liver concentration of carbon-14. Rats were fed cholestyramine in feed for 14 days after administration of (/sup 14/C)PFO and for 21 days after administration of (/sup 14/C)PFOS. Control rats were administered radiolabeled fluorochemical but were not treated with cholestyramine. Cholestyramine treatment increased mean cumulative carbon-14 elimination in feces by 9.8-fold for rats administered (/sup 14/C)PFO and by 9.5-fold for rats administered (/sup 14/C)PFOS. After (/sup 14/C)PFO, a mean of 4% of the dose of carbon-14 was in liver of cholestyramine-treated rats at 14 days versus 7.6% in control rats; after (/sup 14/C)PFOS, 11.3% of the dose was in liver at 21 days versus 40.3% in control rats. After administration of either radiolabeled compound, plasma and red blood cell carbon-14 concentrations, which were relatively lower than liver concentrations, were also significantly reduced by cholestyramine treatment.

  15. Strontium administration in young chickens improves bone volume and architecture but does not enhance bone structural and material strength.

    PubMed

    Shahnazari, M; Lang, D H; Fosmire, G J; Sharkey, N A; Mitchell, A D; Leach, R M

    2007-03-01

    Genetic selection for rapid body growth in broiler chickens has resulted in adverse effects on the skeletal system exemplified by a higher rate of cortical fractures in leg bones. Strontium (Sr) has been reported to have beneficial effects on bone formation and strength. We supplemented the diet of 300-day-old chicks with increasing dosages of Sr (0%, 0.12%, or 0.24%) to study the capacity of the element to improve bone quality and mechanical integrity. Treatment with Sr increased cortical bone volume and reduced bone porosity as measured by micro-computed tomography. The higher level of Sr significantly reduced bone Ca content (34.7%) relative to controls (37.2%), suggesting that Sr replaced some of the Ca in bone. Material properties determined by the three-point bending test showed that bone in the Sr-treated groups withstood greater deformation prior to fracture. Load to failure and ultimate stress were similar across groups. Our results indicate that Sr treatment in rapidly growing chickens induced positive effects on bone volume but did not improve the breaking strength of long bones. PMID:17340224

  16. A New Bioinspired Perchlorate Reduction Catalyst with Significantly Enhanced Stability via Rational Tuning of Rhenium Coordination Chemistry and Heterogeneous Reaction Pathway.

    PubMed

    Liu, Jinyong; Han, Mengwei; Wu, Dimao; Chen, Xi; Choe, Jong Kwon; Werth, Charles J; Strathmann, Timothy J

    2016-06-01

    Rapid reduction of aqueous ClO4(-) to Cl(-) by H2 has been realized by a heterogeneous Re(hoz)2-Pd/C catalyst integrating Re(O)(hoz)2Cl complex (hoz = oxazolinyl-phenolato bidentate ligand) and Pd nanoparticles on carbon support, but ClOx(-) intermediates formed during reactions with concentrated ClO4(-) promote irreversible Re complex decomposition and catalyst deactivation. The original catalyst design mimics the microbial ClO4(-) reductase, which integrates Mo(MGD)2 complex (MGD = molybdopterin guanine dinucleotide) for oxygen atom transfer (OAT). Perchlorate-reducing microorganisms employ a separate enzyme, chlorite dismutase, to prevent accumulation of the destructive ClO2(-) intermediate. The structural intricacy of MGD ligand and the two-enzyme mechanism for microbial ClO4(-) reduction inspired us to improve catalyst stability by rationally tuning Re ligand structure and adding a ClOx(-) scavenger. Two new Re complexes, Re(O)(htz)2Cl and Re(O)(hoz)(htz)Cl (htz = thiazolinyl-phenolato bidentate ligand), significantly mitigate Re complex decomposition by slightly lowering the OAT activity when immobilized in Pd/C. Further stability enhancement is then obtained by switching the nanoparticles from Pd to Rh, which exhibits high reactivity with ClOx(-) intermediates and thus prevents their deactivating reaction with the Re complex. Compared to Re(hoz)2-Pd/C, the new Re(hoz)(htz)-Rh/C catalyst exhibits similar ClO4(-) reduction activity but superior stability, evidenced by a decrease of Re leaching from 37% to 0.25% and stability of surface Re speciation following the treatment of a concentrated "challenge" solution containing 1000 ppm of ClO4(-). This work demonstrates the pivotal roles of coordination chemistry control and tuning of individual catalyst components for achieving both high activity and stability in environmental catalyst applications. PMID:27182602

  17. Significant visible-light photocatalytic enhancement in Rhodamine B degradation of silver orthophosphate via the hybridization of N-doped graphene and poly(3-hexylthiophene).

    PubMed

    Zhang, Yanlin; Xie, Churu; Gu, Feng Long; Wu, Honghai; Guo, Qiang

    2016-09-01

    Organic pollutants as typical water contaminants are potentially harmful to human health. In this study, we suggested that the novel Ag3PO4/N-doped graphene (NG)/Poly(3-hexylthiophene) (P3HT) composites can remove the organic dye Rhodamine B (RhB) from water. This Ag3PO4-based photocatalyst was synthesized via a facile method and subsequently characterized by XRD, SEM, TEM, XPS, Raman spectroscopy, PL spectroscopy, and UV-vis DRS. The photocatalytic activity of Ag3PO4/NG/P3HT composites is significantly higher than that of pristine Ag3PO4, Ag3PO4/NG, and Ag3PO4/P3HT for RhB degradation under visible light irradiation, especially the kinetic constant of Ag3PO4/NG/P3HT is more than 6 times of pristine Ag3PO4. The reactive oxygen species trapping experiments indicate that the degradation of RhB over the Ag3PO4/NG/P3HT composites mainly results from the holes oxidation and superoxide radical reduction. Besides, Ag3PO4/NG/P3HT composites exhibit better recyclability and stability than pristine Ag3PO4. Furthermore, the photocatalytic mechanism of Ag3PO4/NG/P3HT composites for RhB degradation under visible light was proposed as the synergistic effect of irradiated Ag3PO4, P3HT and NG sheets on the effective separation of photogenerated electron-hole pairs, and the enhancement of visible light absorbance. PMID:27152973

  18. Ability of Mn2+ to Permeate the Eye and Availability of Manganese-enhanced Magnetic Resonance Imaging for Visual Pathway Imaging via Topical Administration

    PubMed Central

    Chen, Yao; Shi, Chun-Yan; Li, Ying; Hu, Yun-Tao; Han, Hong-Bin; Sun, Xiao-Dong; Salvi, Satyajeet S; Ma, Zhi-Zhong

    2016-01-01

    Background: Manganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI. Methods: Forty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2 in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices. Results: Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2+ were 5087 ± 666 ng/ml, 22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. Conclusions: The corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous

  19. FLT3 ligand administration after hematopoietic cell transplantation increases circulating dendritic cell precursors that can be activated by CpG oligodeoxynucleotides to enhance T-cell and natural killer cell function.

    PubMed

    Chen, Wei; Chan, Anissa S H; Dawson, Amanda J; Liang, Xueqing; Blazar, Bruce R; Miller, Jeffrey S

    2005-01-01

    Dendritic cells (DCs) are key effectors in innate immunity and play critical roles in triggering adaptive immune responses. FLT3 ligand (FLT3-L) is essential for DC development from hematopoietic progenitors. In a phase I clinical trial, we demonstrated that immunotherapy with subcutaneous injection of FLT3-L is safe and well tolerated in cancer patients recovering from autologous hematopoietic cell transplantation (HCT). FLT3-L administration significantly increased the frequency and absolute number of blood DC precursors without affecting other mature cell lineages during the 6-week course of FLT3-L therapy. After 14 days of FLT3-L administration, the number of blood CD11c + DCs, plasmacytoid DCs (PDCs), and CD14 + monocytes increased by 5.3-, 2.9-, 3.8-fold, respectively, and was maintained at increased levels throughout FLT3-L therapy. FLT3-L-increased blood DCs in HCT patients were immature and had modest enhancing effects on in vitro T-cell proliferation to antigens and natural killer (NK) cell function. The addition of type B CpG oligodeoxynucleotides (ODNs) to peripheral blood mononuclear cells obtained from HCT patients receiving FLT3-L therapy induced rapid maturation of both CD11c + DCs and PDCs and enhanced T-cell proliferative responses. In addition, CpG ODN induced potent activation of NK cells from FLT3-L-treated patients with increased surface CD69 expression and augmented cytotoxicity. CpG ODN-induced activation of NK cells was primarily via an indirect mechanism through PDCs. These findings suggest that FLT3-L mobilization of DC precursors followed by a specific DC stimulus such as CpG ODN may provide a novel strategy to manipulate antitumor immunity in patients after HCT. PMID:15625541

  20. A significant cathodic shift in the onset potential and enhanced photoelectrochemical water splitting using Au nanoparticles decorated WO3 nanorod array.

    PubMed

    Xu, Fang; Yao, Yanwen; Bai, Dandan; Xu, Ruishu; Mei, Jingjing; Wu, Dapeng; Gao, Zhiyong; Jiang, Kai

    2015-11-15

    Au nanoparticles decorated WO3 nanorod array was prepared and applied for solar water oxidation. Scanning electron microscopy and transmission electron microscop images showed that Au distributed on the surface of WO3 nanorod array. The surface plasmon resonance effect of Au nanoparticles contributed to the enhancement of photoelectrochemical performance of Au-WO3 photoanode, such as enhanced photocurrent density of 1.17mA/cm(2) at 1.0V vs Ag/AgCl, a cathodic shift of onset of ∼0.2V and higher stability. UV-vis absorption, electrochemical impedance and Mott-Schottky measurements proved that Au-WO3 photoanode has enhanced light absorption, lower transfer resistance, increased photogenerated carriers density and higher hole injection yield. Therefore, Au-WO3 photoanode exhibited higher photoelectrochemical performance than WO3 photoanode. PMID:26218199

  1. Enhanced Pulmonary Vascular and Alveolar Development via Prenatal Administration of a Slow-Release Synthetic Prostacyclin Agonist in Rat Fetal Lung Hypoplasia

    PubMed Central

    Umeda, Satoshi; Miyagawa, Shigeru; Fukushima, Satsuki; Oda, Noriko; Saito, Atsuhiro; Sakai, Yoshiki; Sawa, Yoshiki; Okuyama, Hiroomi

    2016-01-01

    Lung hypoplasia and pulmonary hypertension are the major causes of mortality in neonates with congenital diaphragmatic hernia (CDH). Although the prostaglandin pathway plays a pivotal role in lung development, the reported efficacy of postnatal prostaglandin agonist treatment is suboptimal. We hypothesized that prenatal treatment with ONO-1301SR, a slow-release form of a novel synthetic prostacyclin agonist with thromboxane inhibitory activity, might enhance the development of lungs exhibiting hypoplasia in the fetal period. On embryonic day (E) 9.5, nitrofen was given to pregnant Sprague-Dawley rats to establish a CDH-related lung hypoplasia model, whereas normal rats received the vehicle only. The same day, either ONO-1301SR or a placebo was also randomly administered. On E21.5, the fetuses of the normal group and those exhibiting CDH were analyzed. Prenatal ONO-1301SR administration had no influence on the incidence of nitrofen-induced CDH. The lung-to-body weight ratio in the CDH+ONO group was greater than that in the CDH group. Histologically, the medial wall in the CDH+ONO group was two-thirds thinner than that in the CDH group. In addition, the number of Ttf-1-positive cells and the capillary density were ≥1.5 times greater in the CDH+ONO group than in the CDH group, and this increase was associated with higher expression of vascular endothelial growth factor and stromal cell-derived factor in the CDH+ONO group, suggesting enhanced development of the alveolar and capillary networks. Thus, prenatal ONO-1301SR was protective against the progression of lung hypoplasia associated with CDH in a nitrofen-induced rat model, indicating the potential of this treatment for pathologies exhibiting lung hypoplasia. PMID:27529478

  2. Enhanced Pulmonary Vascular and Alveolar Development via Prenatal Administration of a Slow-Release Synthetic Prostacyclin Agonist in Rat Fetal Lung Hypoplasia.

    PubMed

    Umeda, Satoshi; Miyagawa, Shigeru; Fukushima, Satsuki; Oda, Noriko; Saito, Atsuhiro; Sakai, Yoshiki; Sawa, Yoshiki; Okuyama, Hiroomi

    2016-01-01

    Lung hypoplasia and pulmonary hypertension are the major causes of mortality in neonates with congenital diaphragmatic hernia (CDH). Although the prostaglandin pathway plays a pivotal role in lung development, the reported efficacy of postnatal prostaglandin agonist treatment is suboptimal. We hypothesized that prenatal treatment with ONO-1301SR, a slow-release form of a novel synthetic prostacyclin agonist with thromboxane inhibitory activity, might enhance the development of lungs exhibiting hypoplasia in the fetal period. On embryonic day (E) 9.5, nitrofen was given to pregnant Sprague-Dawley rats to establish a CDH-related lung hypoplasia model, whereas normal rats received the vehicle only. The same day, either ONO-1301SR or a placebo was also randomly administered. On E21.5, the fetuses of the normal group and those exhibiting CDH were analyzed. Prenatal ONO-1301SR administration had no influence on the incidence of nitrofen-induced CDH. The lung-to-body weight ratio in the CDH+ONO group was greater than that in the CDH group. Histologically, the medial wall in the CDH+ONO group was two-thirds thinner than that in the CDH group. In addition, the number of Ttf-1-positive cells and the capillary density were ≥1.5 times greater in the CDH+ONO group than in the CDH group, and this increase was associated with higher expression of vascular endothelial growth factor and stromal cell-derived factor in the CDH+ONO group, suggesting enhanced development of the alveolar and capillary networks. Thus, prenatal ONO-1301SR was protective against the progression of lung hypoplasia associated with CDH in a nitrofen-induced rat model, indicating the potential of this treatment for pathologies exhibiting lung hypoplasia. PMID:27529478

  3. Overexpression of BDNF in the ventral tegmental area enhances binge cocaine self-administration in rats exposed to repeated social defeat.

    PubMed

    Wang, Junshi; Bastle, Ryan M; Bass, Caroline E; Hammer, Ronald P; Neisewander, Janet L; Nikulina, Ella M

    2016-10-01

    Stress is a major risk factor for substance abuse. Intermittent social defeat stress increases drug self-administration (SA) and elevates brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA) in rats. Intra-VTA BDNF overexpression enhances social defeat stress-induced cross-sensitization to psychostimulants and induces nucleus accumbens (NAc) ΔFosB expression. Therefore, increased VTA BDNF may mimic or augment the development of drug abuse-related behavior following social stress. To test this hypothesis, adeno-associated virus (AAV) was infused into the VTA to overexpress either GFP alone (control) or GFP + BDNF. Rats were then either handled or exposed to intermittent social defeat stress before beginning cocaine SA training. The SA acquisition and maintenance phases were followed by testing on a progressive ratio (PR) schedule of cocaine reinforcement, and then during a 12-h access "binge" cocaine SA session. BDNF and ΔFosB were quantified postmortem in regions of the mesocorticolimbic circuitry using immunohistochemistry. Social defeat stress increased cocaine intake on a PR schedule, regardless of virus treatment. While stress alone increased intake during the 12-h binge session, socially-defeated rats that received VTA BDNF overexpression exhibited even greater cocaine intake compared to the GFP-stressed group. However, VTA BDNF overexpression alone did not alter binge intake. BDNF expression in the VTA was also positively correlated with total cocaine intake during binge session. VTA BDNF overexpression increased ΔFosB expression in the NAc, but not in the dorsal striatum. Here we demonstrate that VTA BDNF overexpression increases long-access cocaine intake, but only under stressful conditions. Therefore, enhanced VTA-BDNF expression may be a facilitator for stress-induced increases in drug abuse-related behavior specifically under conditions that capture compulsive-like drug intake. PMID:27154426

  4. Expression of a maize Myb transcription factor driven by a putative silk-specific promoter significantly enhances resistance to Helicoverpa zea in transgenic maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hi II maize (Zea mays) plants were engineered to express maize p1 cDNA, a Myb transcription factor, controlled by a putative silk specific promoter, for secondary metabolite production and corn earworm resistance. Transgene expression did not enhance silk color, but about half of the transformed p...

  5. Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

    PubMed

    Kikuchi, Yosuke; Kunitoh-Asari, Ayami; Hayakawa, Katsuyuki; Imai, Shinjiro; Kasuya, Kenji; Abe, Kimio; Adachi, Yu; Fukudome, Shin-Ichi; Takahashi, Yoshimasa; Hachimura, Satoshi

    2014-01-01

    The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+) B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection. PMID:24466081

  6. Diphenyl diselenide administration enhances cortical mitochondrial number and activity by increasing hemeoxygenase type 1 content in a methylmercury-induced neurotoxicity mouse model.

    PubMed

    Glaser, Viviane; Martins, Roberta de Paula; Vieira, Ana Julia Hoffmann; Oliveira, Eliana de Medeiros; Straliotto, Marcos Raniel; Mukdsi, Jorge Humberto; Torres, Alicia Inés; de Bem, Andreza Fabro; Farina, Marcelo; da Rocha, João Batista Teixeira; De Paul, Ana Lucia; Latini, Alexandra

    2014-05-01

    Interest in biochemistry of organoselenium compound has increased in the last decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of diphenyl diselenide (PhSe)2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Swiss male mice were divided into four experimental groups: control, (PhSe)2 (5 μmol/kg, subcutaneous administration), MeHg (40 mg/L, in tap water), and MeHg + (PhSe)2. After the treatment (21 days), the animals were killed and the cerebral cortex was analyzed. Electron microscopy indicated an enlarged and fused mitochondria leading to a reduced number of organelles, in the MeHg-exposed mice. Furthermore, cortical creatine kinase activity, a sensitive mitochondrial oxidative stress sensor, was almost abolished by MeHg. Subcutaneous (PhSe)2 co-treatment rescued from MeHg-induced mitochondrial alterations. (PhSe)2 also behaved as an enhancer of mitochondrial biogenesis, by increasing cortical mitochondria content in mouse-receiving (PhSe)2 alone. Mechanistically, (PhSe)2 (1 μM; 24 h) would trigger the cytoprotective Nrf-2 pathway for activating target genes, since astroglial cells exposed to the chalcogen showed increased content of hemeoxygenase type 1, a sensitive marker of the activation of this via. Thus, it is proposed that the (PhSe)2-neuroprotective effect might be linked to its mitoprotective activity. PMID:24623265

  7. Study on the pharmacokinetics profiles of polyphyllin I and its bioavailability enhancement through co-administration with P-glycoprotein inhibitors by LC-MS/MS method.

    PubMed

    Zhu, He; Zhu, Si-Can; Shakya, Shailendra; Mao, Qian; Ding, Chuan-Hua; Long, Min-Hui; Li, Song-Lin

    2015-03-25

    Polyphyllin I (PPI), one of the steroidal saponins in Paris polyphylla, is a promising natural anticancer candidate. Although the anticancer activity of PPI has been well demonstrated, information regarding the pharmacokinetics and bioavailability is limited. In this study, a series of reliable and rapid liquid chromatography-tandem mass spectrometry methods were developed and successfully applied to determinate PPI in rat plasma, cell incubation media and cell homogenate. Then the pharmacokinetics of PPI in rats was studied and the result revealed that PPI was slowly eliminated with low oral bioavailability (about 0.62%) at a dose of 50 mg/kg, and when co-administrated with verapamil (VPL) and cyclosporine A (CYA), the oral bioavailability of PPI could increase from 0.62% to 3.52% and 3.79% respectively. In addition, in vitro studies showed that with the presence of VPL and CYA in Caco-2 cells, the efflux ratio of PPI decreased from 12.5 to 2.96 and 2.22, and the intracellular concentrations increased 5.8- and 5.0-fold respectively. These results demonstrated that PPI, with poor oral bioavailability, is greatly impeded by P-gp efflux, and inhibition of P-gp can enhance its bioavailability. PMID:25590941

  8. Significant Treasures.

    ERIC Educational Resources Information Center

    Andrews, Ian A.

    1999-01-01

    Provides a crossword puzzle with an answer key corresponding to the book entitled "Significant Treasures/Tresors Parlants" that is filled with color and black-and-white prints of paintings and artifacts from 131 museums and art galleries as a sampling of the 2,200 such Canadian institutions. (CMK)

  9. ARRA Investments in Technology, Innovation, and K-12 Reform: The Digital Education Funding Cliff. A Preliminary Report on State Administration of the American Recovery & Reinvestment Act of 2009: Enhancing Education Through Technology Program

    ERIC Educational Resources Information Center

    State Educational Technology Directors Association, 2010

    2010-01-01

    This is the first in a forthcoming series of reports documenting state administration of educational technology funding included in the "American Recovery and Reinvestment Act of 2009" (ARRA). The ARRA included a $650 million allocation in ESEA Title II, Part D, commonly referred to as the "Enhancing Education through Technology program" (EETT).…

  10. Intravenous administration of adipose tissue-derived stem cells enhances nerve healing and promotes BDNF expression via the TrkB signaling in a rat stroke model

    PubMed Central

    Li, Xin; Zheng, Wei; Bai, Hongying; Wang, Jin; Wei, Ruili; Wen, Hongtao; Ning, Hanbing

    2016-01-01

    Previous studies have shown the beneficial effects of adipose-derived stem cells (ADSCs) transplantation in stroke. However, the molecular mechanism by which transplanted ADSCs promote nerve healing is not yet elucidated. In order to make clear the molecular mechanism for the neuroprotective effects of ADSCs and investigate roles of the BDNF–TrkB signaling in neuroprotection of ADSCs, we, therefore, examined the neurological function, brain water content, and the protein expression in middle cerebral artery occlusion (MCAO) rats with or without ADSCs transplantation. ADSCs were transplanted intravenously into rats at 30 minutes after MCAO. K252a, an inhibitor of TrkB, was administered into rats by intraventricular and brain stereotaxic injection. Modified neurological severity score tests were performed to measure behavioral outcomes. The results showed that ADSCs significantly alleviated neurological deficits and reduced brain water content in MCAO rats. The protein expression levels of BDNF and TrkB significantly increased in the cortex of MCAO rats with ADSCs treatment. However, K252a administration reversed the ADSCs-induced elevation of BDNF, TrkB, and Bcl-2 and reduction of Bax protein in MCAO rats. ADSCs promote BDNF expression via the TrkB signaling and improve functional neurological recovery in stroke rats. PMID:27330296

  11. Supramolecular polymer hydrogels from bolaamphiphilic L-histidine and benzene dicarboxylic acids: thixotropy and significant enhancement of Eu(III) fluorescence.

    PubMed

    Liu, Yaqing; Wang, Tianyu; Liu, Minghua

    2012-11-12

    Supramolecular polymers from the bolaamphiphilic L-histidine (BolaHis) and benzene dicarboxylic acids (o-phthalic acid, OPA; isophthalic acid, IPA and terephthalic acid, TPA) were found to form hydrogels although neither of the single components could gel water. It was suggested that the hydrogen bond and ionic interactions among different imidazole and carboxylic acid groups are responsible for the formation of the supramolecular polymer as well as the hydrogel formation. Depending on the structures of the dicarboxylic acids, different behaviors of the gels were observed. The hydrogels from OPA/BolaHis and IPA/BolaHis showed thixotropic properties, that is, the hydrogel was destroyed by hand shaking and then slowly gelated again at room temperature. However, the hydrogels of TPA/BolaHis could not. Interestingly, when Eu(III) was doped into IPA/BolaHis supramolecular polymers, very strong luminescence enhancement was observed. FT-IR spectroscopies and XRD analysis revealed that the strong luminescence enhancement could be attributed to the matched supramolecular nanostructures, which render the correct binding and a good dispersion of Eu(III) ions. The work offers a new approach for fabricating functional hydrogels through the supramolecular polymers. PMID:23097314

  12. Au plasmonics in a WS{sub 2}-Au-CuInS{sub 2} photocatalyst for significantly enhanced hydrogen generation

    SciTech Connect

    Cheng, Zhongzhou; Wang, Zhenxing E-mail: hej@nanoctr.cn; Shifa, Tofik Ahmed; Wang, Fengmei; Zhan, Xueying; Xu, Kai; He, Jun E-mail: hej@nanoctr.cn; Liu, Quanlin

    2015-11-30

    Promoting the activities of photocatalysts is still the critical challenge in H{sub 2} generation area. Here, a Au plasmon enhanced photocatalyst of WS{sub 2}-Au-CuInS{sub 2} is developed by inserting Au nanoparticles between WS{sub 2} nanotubes and CuInS{sub 2} (CIS) nanoparticles. Due to the localized surface plasmonic resonance properties from Au nanoparticles, WS{sub 2}-Au-CIS shows the best performance as compared to Au-CIS, CIS, WS{sub 2}-CIS, CIS-Au, WS{sub 2}-Au, and WS{sub 2}-CIS-Au. The surface plasmonic resonance effects dramatically intensify the absorption of visible light and help to inject hot electrons into the semiconductors. Our findings open up an efficient method to optimize the type-II structures for photocatalytic water splitting.

  13. Phase stabilization of magnetite (Fe3O4) nanoparticles with B2O3 addition: A significant enhancement on the phase transition temperature

    NASA Astrophysics Data System (ADS)

    Topal, Uğur; Aksan, Mehmet Ali

    2016-05-01

    Magnetite nanoparticles (MNPs) are extensively investigated for biomedical applications, particularly as contrast agents for Magnetic Resonance Imaging and as drug delivery agent and heat mediators for cancer therapy. Tuning the magnetic properties of the magnetite nanoparticles with doping of foreign atoms has a crucial importance for determining the application areas of these materials and so attracts much interests. On the other hand the doping with foreign atoms requires high temperature annealing, and it causes a phase transition to the hematite phase above 400 °C. In this work the phase transition temperature from the magnetite to the hematite phase has been increased by 200 °C, which is the highest enhancement reported in literature. It was achieved by addition of the appropriate amounts of B2O3. Our experiments indicates that the 5.0 wt% of B2O3 addition stabilizes and keeps the existence of single phase magnetite up to 600 °C.

  14. Conjugation of an anti transferrin receptor IgG3-avidin fusion protein with biotinylated saporin results in significant enhancement of its cytotoxicity against malignant hematopoietic cells.

    PubMed

    Daniels, Tracy R; Ng, Patrick P; Delgado, Tracie; Lynch, Maureen R; Schiller, Gary; Helguera, Gustavo; Penichet, Manuel L

    2007-11-01

    We have previously developed an antibody fusion protein composed of a mouse/human chimeric IgG3 specific for the human transferrin receptor genetically fused to avidin (anti-hTfR IgG3-Av) as a universal delivery system for cancer therapy. This fusion protein efficiently delivers biotinylated FITC into cancer cells via TfR-mediated endocytosis. In addition, anti-hTfR IgG3-Av alone exhibits intrinsic cytotoxic activity and interferes with hTfR recycling, leading to the rapid degradation of the TfR and lethal iron deprivation in certain malignant B-cell lines. We now report on the cytotoxic effects of a conjugate composed of anti-hTfR IgG3-Av and biotinylated saporin 6 (b-SO6), a toxin derived from the plant Saponaria officinalis that inhibits protein synthesis. Conjugation of anti-hTfR IgG3-Av with b-SO6 enhances the cytotoxic effect of the fusion protein in sensitive cells and also overcomes the resistance of malignant cells that show low sensitivity to the fusion protein alone. Our results show for the first time that loading anti-hTfR IgG3-Av with a biotinylated toxin enhances the cytotoxicity of the fusion protein alone. These results suggest that anti-hTfR IgG3-Av has great potential as a therapeutic agent for a wide range of applications due to its intrinsic cytotoxic activity plus its ability to deliver biotinylated molecules into cancer cells. PMID:18025284

  15. The Significance of National Association for the Education of Young Children Accreditation in Elevating Quality of Early Childhood Education: Administrators', Teachers', and Parents' Beliefs about Accreditation and Its Process

    ERIC Educational Resources Information Center

    Vardanyan, Kristine

    2013-01-01

    The following is a doctoral dissertation that studied administrators', teachers', and parents' perceptions and attitudes related to an early childhood center/preschool accreditation experience. A qualitative case study of one preschool center focused on the influence that the decision to pursue accreditation and implement the National Association…

  16. Postmortem aging can significantly enhance water-holding capacity of broiler pectoralis major muscle measured by the salt-induced swelling/centrifuge method

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Water-holding capacity (WHC) is one of the most important functional properties of fresh meat and can be significantly affected by postmortem muscle changes. Two experiments were carried out to evaluate the effects of postmortem aging on WHC of broiler pectoralis (p.) major muscle indicated with % s...

  17. Increasing the clozapine: norclozapine ratio with co-administration of fluvoxamine to enhance efficacy and minimize side effects of clozapine therapy.

    PubMed

    Légaré, Nancy; Grégoire, Claire-Anne; De Benedictis, Luigi; Dumais, Alexandre

    2013-06-01

    Although clozapine is the only antipsychotic agent to have demonstrated superior efficacy in treatment-refractory schizophrenia, one- to two-thirds of patients do not respond adequately despite acceptable dosages and plasma levels. Moreover, a significant number of patients stop the therapy for various reasons, including its side effects, many of which are thought to be related to its active metabolite, norclozapine. However, combining clozapine with the SSRI antidepressant fluvoxamine decreases norclozapine formation by inhibiting the CYP450 1A2 isoenzyme. Lowering norclozapine levels in this way while maintaining therapeutic clozapine levels increases the clozapine: norclozapine ratio; the potential benefits include both a reduction of such side effects as sedation, weight gain, metabolic disturbances, and neutropenia, and an increase in efficacy. The optimal ratio of clozapine to norclozapine has not yet been defined, but a ratio of two or more implies that saturation of clozapine metabolism has been reached. We hypothesize that co-administration of clozapine and fluvoxamine at dosages that will produce therapeutic plasma levels of clozapine and a clozapine: norclozapine ratio of two or more will increase efficacy and tolerability of clozapine therapy in treatment-resistant schizophrenic patients. PMID:23490199

  18. Enhancement in number and function of antigen-presenting cells in the lymphatic tissue of rats after in vivo administration of diphenylhydantoin (DPH).

    PubMed Central

    Petrasch, S; Wacker, H H; Zou, P; Bechtold, D; Brittinger, G

    1989-01-01

    We present a monoclonal IgG1 antibody, KiMy1R, which is specific for macrophages and their derivatives in the lymphatic tissue of the rat, and evaluate the distribution of subsets of mononuclear cells in popliteal and para-aortal lymph nodes of Wistar rats after injection of 50 mg DPH into the hindpads. Compared with resting lymphatic tissue and lymph nodes of animals treated with phenobarbital, DPH induced a significant increase (P less than 0.01) of the proportion of phagocytic cells. Furthermore, the soluble antigen alkaline phosphatase was traced after inoculation into the footpads of rats: in locoregional lymph nodes the percentage (mean 12.8/10(3] and the total number (mean 476 x 10(3) cells/lymph node) of cells with membrane-bound or intracytoplasmic alkaline phosphatase, as detected by a monoclonal anti-alkaline phosphatase antibody, were significantly higher (P less than 0.001) in animals pretreated with DPH than in rats pretreated with phenobarbital (mean 2.1/10(3); 31.2 x 10(3) cells/lymph node) and in untreated animals (mean 1.9/10(3); 4.1 x 10(3) cells/lymph node). If verified in humans, the effect of DPH in enhancing the number and function of macrophages and other antigen-presenting cells may exert favourable effects in patients with impairment of the mononuclear phagocytic system. Images Fig. 1 PMID:2805417

  19. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: Long-term results of the ARCOSEIN multicenter randomized study

    SciTech Connect

    Toledano, Alain . E-mail: alain.toledano@gmail.com; Garaud, Pascal; Serin, Daniel; Fourquet, Alain; Bosset, Jean-Francois; Breteau, Noel; Body, Gilles; Azria, David; Le Floch, Olivier; Calais, Gilles

    2006-06-01

    Purpose: In 1996, a multicenter randomized study was initiated that compared sequential vs. concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) after breast-conserving surgery (ARCOSEIN study). After a median follow-up of 6.7 years (range, 4.3-9 years), we decided to prospectively evaluate the late effects of these 2 strategies. Methods and Materials: A total of 297 patients from the 5 larger participating institutions were asked to report for a follow-up examination. Seventy-two percent (214 patients) were eligible for evaluation of late toxicity. After breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (Arm A) or CT administered concurrently with RT (Arm B). In all patients, CT regimen consisted of mitoxantrone (12 mg/m{sup 2}), 5-FU (500 mg/m{sup 2}), and cyclophosphamide (500 mg/m{sup 2}), 6 cycles (Day 1 to Day 21). Conventional RT was delivered to the whole breast by administration of a 2 Gy per fraction protocol to a total dose of 50 Gy ({+-} boost to the primary tumor bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist, according to the LENT/SOMA scale. Skin pigmentation was also evaluated according to a personal 5-points scoring system (excellent, good, moderate, poor, very poor). Results: Among the 214 evaluable patients, 107 were treated in each arm. The 2 populations were homogeneous for patient, tumor, and treatment characteristics. Subcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in Arm B. No statistical difference was observed between the 2 arms of the study concerning Grade 2 or higher pain, breast edema, or lymphedema. No deaths were caused by late toxicity. Conclusion: After breast-conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of Grade 2 or greater late side effects.

  20. Significant enhancement of gas uptake capacity and selectivity via the judicious increase of open metal sites and Lewis basic sites within two polyhedron-based metal-organic frameworks.

    PubMed

    Liu, Bing; Yao, Shuo; Shi, Chao; Li, Guanghua; Huo, Qisheng; Liu, Yunling

    2016-02-21

    Two new isomorphous polyhedron-based MOFs ( and ), with dual functionalities of OMSs and LBSs, have been synthesized by using the SBB strategy. By judiciously avoiding the DABCO axial ligand, possesses more OMSs than , and exhibits a significant enhancement of CO2 uptake capacity 210 versus 162 cm(3) g(-1) for at 273 K under 1 bar. PMID:26809833

  1. Significantly enhanced dye removal performance of hollow tin oxide nanoparticles via carbon coating in dark environment and study of its mechanism

    PubMed Central

    2014-01-01

    Understanding the correlation between physicochemical properties and morphology of nanostructures is a prerequisite for widespread applications of nanomaterials in environmental application areas. Herein, we illustrated that the uniform-sized SnO2@C hollow nanoparticles were large-scale synthesized by a facile hydrothermal method. The size of the core-shell hollow nanoparticles was about 56 nm, and the shell was composed of a solid carbon layer with a thickness of 2 ~ 3 nm. The resulting products were characterized in terms of morphology, composition, and surface property by various analytical techniques. Moreover, the SnO2@C hollow nanoparticles are shown to be effective adsorbents for removing four different dyes from aqueous solutions, which is superior to the pure hollow SnO2 nanoparticles and commercial SnO2. The enhanced mechanism has also been discussed, which can be attributed to the high specific surface areas after carbon coating. PMID:25221462

  2. Two-step grafting significantly enhances the survival of foetal dopaminergic transplants and induces graft-derived vascularisation in a 6-OHDA model of Parkinson's disease.

    PubMed

    Büchele, Fabian; Döbrössy, Máté; Hackl, Christina; Jiang, Wei; Papazoglou, Anna; Nikkhah, Guido

    2014-08-01

    Following transplantation of foetal primary dopamine (DA)-rich tissue for neurorestaurative treatment of Parkinson's disease (PD), only 5-10% of the functionally relevant DAergic cells survive both in experimental models and in clinical studies. The current work tested how a two-step grafting protocol could have a positive impact on graft survival. DAergic tissue is divided in two portions and grafted in two separate sessions into the same target area within a defined time interval. We hypothesized that the first graft creates a "DAergic" microenvironment or "nest" similar to the perinatal substantia nigra that stimulates and protects the second graft. 6-OHDA-lesioned rats were sequentially transplanted with wild-type (GFP-, first graft) and transgenic (GFP+, second graft) DAergic cells in time interims of 2, 5 or 9days. Each group was further divided into two sub-groups receiving either 200k (low cell number groups: 2dL, 5dL, 9dL) or 400k cells (high cell number groups: 2dH, 5dH, 9dH) as first graft. During the second transplantation, all groups received the same amount of 200k GFP+ cells. Controls received either low or high cell numbers in one single session (standard protocol). Drug-induced rotations, at 2 and 6weeks after grafting, showed significant improvement compared to the baseline lesion levels without significant differences between the groups. Rats were sacrificed 8weeks after transplantation for post-mortem histological assessment. Both two-step groups with the time interval of 2days (2dL and 2dH) showed a significantly higher survival of DAergic cells compared to their respective standard control group (2dL, +137%; 2dH, +47%). Interposing longer intervals of 5 or 9days resulted in the loss of statistical significance, neutralising the beneficial two-step grafting effect. Furthermore, the transplants in the 2dL and 2dH groups had higher graft volume and DA-fibre-density values compared to all other two-step groups. They also showed intense growth of

  3. Administrative Synergy

    ERIC Educational Resources Information Center

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2012-01-01

    One of the biggest obstacles to overcome in creating and sustaining an administrative professional learning community (PLC) is time. Administrators are constantly deluged by the tyranny of the urgent. It is a Herculean task to carve out time for PLCs, but it is imperative to do so. In this article, the authors describe how an administrative PLC…

  4. Significantly enhanced tumor cellular and lysosomal hydroxychloroquine delivery by smart liposomes for optimal autophagy inhibition and improved antitumor efficiency with liposomal doxorubicin.

    PubMed

    Wang, Yang; Shi, Kairong; Zhang, Li; Hu, Guanlian; Wan, Jingyu; Tang, Jiajing; Yin, Sheng; Duan, Jiandong; Qin, Ming; Wang, Neng; Xie, Dandan; Gao, Xinle; Gao, Huile; Zhang, Zhirong; He, Qin

    2016-06-01

    Hydroxychloroquine (HCQ) inhibits autophagy and therefore can sensitize some cancer cells to chemotherapy, but the high doses required limit its clinical use. Here we show that loading HCQ into liposomes (HCQ/Lip) decorated with a pH-sensitive TH-RGD targeting peptide (HCQ/Lip-TR) can concentrate HCQ in B16F10 tumor cells and lysosomes. HCQ/Lip-TR was efficiently internalized as a result of its ability to bind ITGAV-ITGB3/integrin αvβ3 receptors highly expressed on the tumor cell surface and to undergo charge reversal from anionic at pH 7.4 to cationic at pH 6.5. Studies in vitro at pH 6.5 showed that the intracellular HCQ concentration was 35.68-fold higher, and lysosomal HCQ concentration 32.22-fold higher, after treating cultures with HCQ/Lip-TR than after treating them with free HCQ. The corresponding enhancements observed in mice bearing B16F10 tumors were 15.16-fold within tumor cells and 14.10-fold within lysosomes. HCQ/Lip-TR was associated with milder anemia and milder myosuppressive reductions in white blood cell and platelet counts than free HCQ, as well as less accumulation in the small intestine, which may reduce risk of intestinal side effects. In addition, co-delivering HCQ/Lip-TR with either free doxorubicin (DOX) or liposomal DOX improved the ability of DOX to inhibit tumor growth. Biochemical, electron microscopy and immunofluorescence experiments confirmed that HCQ/Lip-TR blocked autophagic flux in tumor cells. Our results suggest that loading HCQ into Lip-TR liposomes may increase the effective concentration of the inhibitor in tumor cells, allowing less toxic doses to be used. PMID:27123811

  5. Inclusion of a universal tetanus toxoid CD4+ T cell epitope P2 significantly enhanced the immunogenicity of recombinant rotavirus ΔVP8* subunit parenteral vaccines

    PubMed Central

    Wen, Xiaobo; Wen, Ke; Cao, Dianjun; Li, Guohua; Jones, Ronald W.; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka; Yuan, Lijuan

    2014-01-01

    Currently available live oral rotavirus vaccines, Rotarix® and RotaTeq®, are highly efficacious in developed countries. However, the immunogenicity and efficacy of such vaccines in some developing countries are low. We reported previously that bacterially-expressed rotavirus ΔVP8* subunit vaccine candidates with P[8], P[4] or P[6] specificity elicited high-titer virus neutralizing antibodies in animals immunized intramuscularly. Of note was the finding that antibodies induced with the P[8]ΔVP8* vaccine neutralized both homotypic P[8] and heterotypic P[4] rotavirus strains to high titer. To further improve its vaccine potential, a tetanus toxoid universal CD4+ T cell epitope P2 was introduced into P[8] or P[6]ΔVP8* construct. The resulting recombinant fusion proteins expressed in Escherichia coli were of high solubility and were produced with high yield. Two doses (10 or 20μg/dose) of the P2-P[8]ΔVP8* vaccine or P2-P[6]ΔVP8* vaccine with aluminum phosphate adjuvant elicited significantly higher geometric mean homologous neutralizing antibody titers than the vaccines without P2 in intramuscularly immunized guinea pigs. Interestingly, high levels of neutralizing antibody responses induced in guinea pigs with 3 doses of the P2-P[8]ΔVP8* vaccine persisted for at least 6 months. Furthermore, in the gnotobiotic piglet challenge study, three intramuscular doses (50μg/dose) of the P2-P[8]ΔVP8* vaccine with aluminum phosphate adjuvant significantly delayed the onset of diarrhea and significantly reduced the duration of diarrhea and the cumulative diarrhea score after oral challenge with virulent human rotavirus Wa (G1P[8]) strain. The P2-P[8]ΔVP8* vaccine induced serum virus neutralizing antibody and VP4-specific IgG antibody production prechallenge, and primed the pigs for higher antibody and intestinal and systemic virus-specific IFN-γ producing CD4+ T cell responses postchallenge. These two subunit vaccines could be used at a minimum singly or preferably in

  6. Intra-accumbens shell injections of SR48692 enhanced cocaine self-administration intake in rats exposed to an environmentally-elicited reinstatement paradigm.

    PubMed

    Ramos-Ortolaza, Dinah L; Negrón, Alejandro; Cruz, Daryana; Falcón, Edgardo; Iturbe, Mari Carmen; Cajigas, Mariela Hernández; Maldonado-Vlaar, Carmen S

    2009-07-14

    Neurotensin (NT) is a neuropeptide involved in cocaine reward, and in learning and memory processes related to drug use within the mesolimbic dopamine (DA) system. Studies have demonstrated that NT receptor antagonists have potential as pharmacotherapeutical tools for cocaine abuse. Therefore, it is important to understand the molecular profile of NT within mesolimbic neurons and the behavioral effects of NT receptor inhibitors on environmentally-elicited cocaine seeking behavior. To address this issue, male Sprague Dawley rats were trained to self-administer cocaine and to discriminate between environmental cues signaling cocaine vs. saline availability. Then, following extinction, these cues were used to induce reinstatement of cocaine seeking behavior. A differential expression profile was observed throughout the experiment. Particularly, a significant increase of NT levels was observed within the nucleus accumbens (NAc) shell subregion during the acquisition phase of training. To further examine the implications of this increase, separate groups of animals received intra NAc shell injections of one of three doses (25, 50, 100 nM) of the NT1 receptor antagonist SR48692 after reaching stable self-administration. Animals were injected prior to placement in the operant conditioning chambers for four consecutive sessions. An increase in lever pressing was observed following antagonist treatment, whereas no major changes in locomotor activity were observed. We propose that the observed increase in lever pressing may be a compensatory response to a decrease in reinforcement, possibly due to decreased DA release, as previous studies show that chronic SR48692 decreases basal DA release in the NAc shell. PMID:19442653

  7. Glu-Trp-ONa or its acylated analogue (R-Glu-Trp-ONa) administration enhances the wound healing in the model of chronic skin wounds in rabbits

    PubMed Central

    Shevtsov, Maxim A; Smagina, Larisa V; Kudriavtceva, Tatiana A; Petlenko, Sergey V; Voronkina, Irina V

    2015-01-01

    The management of chronic skin wounds represents a major therapeutic challenge. The synthesized dipeptide (Glu-Trp-ONa) and its acylated analogue (R-Glu-Trp-ONa) were assessed in the model of nonhealing dermal wounds in rabbits in relation to their healing properties in wound closure. Following wound modeling, the rabbits received a course of intraperitoneal injections of Glu-Trp-ONa or R-Glu-Trp-ONa. Phosphate-buffered saline and Solcoseryl® were applied as negative and positive control agents, respectively. An injection of Glu-Trp-ONa and R-Glu-Trp-ONa decreased the period of wound healing in animals in comparison to the control and Solcoseryl-treated groups. Acylation of Glu-Trp-ONa proved to be beneficial as related to the healing properties of the dipeptide. Subsequent zymography analyses showed that the applied peptides decreased the proteolytic activity of matrix metalloproteinases MMP-9, MMP-8, and MMP-2 in the early inflammatory phase and reversely increased the activity of MMP-9, MMP-8, and MMP-1 in the remodeling phase. Histological analyses of the wound sections (hematoxylin–eosin, Mallory’s staining) confirmed the enhanced formation of granulation tissue and re-epithelialization in the experimental groups. By administering the peptides, wound closures increased significantly through the modulation of the MMPs’ activity, indicating their role in wound healing. PMID:25848208

  8. Significantly enhanced heme retention ability of myoglobin engineered to mimic the third covalent linkage by nonaxial histidine to heme (vinyl) in synechocystis hemoglobin.

    PubMed

    Uppal, Sheetal; Salhotra, Shikha; Mukhi, Nitika; Zaidi, Fatima Kamal; Seal, Manas; Dey, Somdatta Ghosh; Bhat, Rajiv; Kundu, Suman

    2015-01-23

    Heme proteins, which reversibly bind oxygen and display a particular fold originally identified in myoglobin (Mb), characterize the "hemoglobin (Hb) superfamily." The long known and widely investigated Hb superfamily, however, has been enriched by the discovery and investigation of new classes and members. Truncated Hbs typify such novel classes and exhibit a distinct two-on-two α-helical fold. The truncated Hb from the freshwater cyanobacterium Synechocystis exhibits hexacoordinate heme chemistry and bears an unusual covalent bond between the nonaxial His(117) and a heme porphyrin 2-vinyl atom, which remains tightly associated with the globin unlike any other. It seems to be the most stable Hb known to date, and His(117) is the dominant force holding the heme. Mutations of amino acid residues in the vicinity did not influence this covalent linkage. Introduction of a nonaxial His into sperm whale Mb at the topologically equivalent position and in close proximity to vinyl group significantly increased the heme stability of this prototype globin. Reversed phase chromatography, electrospray ionization-MS, and MALDI-TOF analyses confirmed the presence of covalent linkage in Mb I107H. The Mb mutant with the engineered covalent linkage was stable to denaturants and exhibited ligand binding and auto-oxidation rates similar to the wild type protein. This indeed is a novel finding and provides a new perspective to the evolution of Hbs. The successful attempt at engineering heme stability holds promise for the production of stable Hb-based blood substitute. PMID:25451928

  9. Significantly enhanced critical current density in nano-MgB2 grains rapidly formed at low temperature with homogeneous carbon doping

    NASA Astrophysics Data System (ADS)

    Liu, Yongchang; Lan, Feng; Ma, Zongqing; Chen, Ning; Li, Huijun; Barua, Shaon; Patel, Dipak; Shahriar, M.; Hossain, Al; Acar, S.; Kim, Jung Ho; Xue Dou, Shi

    2015-05-01

    High performance MgB2 bulks using carbon-coated amorphous boron as a boron precursor were fabricated by Cu-activated sintering at low temperature (600 °C, below the Mg melting point). Dense nano-MgB2 grains with a high level of homogeneous carbon doping were formed in these MgB2 samples. This type of microstructure can provide a stronger flux pinning force, together with depressed volatility and oxidation of Mg owing to the low-temperature Cu-activated sintering, leading to a significant improvement of critical current density (Jc) in the as-prepared samples. In particular, the value of Jc for the carbon-coated (Mg1.1B2)Cu0.05 sample prepared here is even above 1 × 105 A cm-2 at 20 K, 2 T. The results herein suggest that the combination of low-temperature Cu-activated sintering and employment of carbon-coated amorphous boron as a precursor could be a promising technique for the industrial production of practical MgB2 bulks or wires with excellent Jc, as the carbon-coated amorphous boron powder can be produced commercially at low cost, while the addition of Cu is very convenient and inexpensive.

  10. Significant enhancement of optical absorption through nano-structuring of copper based oxide semiconductors: possible future materials for solar energy applications.

    PubMed

    Bhaumik, Anagh; Shearin, Austin M; Patel, Rishi; Ghosh, Kartik

    2014-06-14

    The optical absorption coefficient is a crucial parameter in determining solar cell efficiency under operational conditions. It is well known that inorganic nanocrystals are a benchmark model for solar cell nanotechnology, given that the tunability of optical properties and stabilization of specific phases are uniquely possible at the nanoscale. A hydrothermal method was employed to fabricate nanostructured copper oxides where the shape, size and phase were tailored by altering the growth parameters, namely the base media used, the reaction temperature, and the reaction time. The nano crystalline structures, phases, morphology, molecular vibrational modes, and optical properties were investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, photoluminescence (PL), and UV-vis spectroscopy. A significantly large optical absorption coefficient, of the order of twice that of Si in the visible range, was observed in a particular phase mixture of nanostructured copper oxides. An optical absorption coefficient of 7.05 10(+5) cm(-1) at 525 nm was observed in a particular nanostructured phase mixture of copper oxides which is appreciably larger than commercially pure CuO (1.19 10(+5) cm(-1)) and Si (1.72 10(+5) cm(-1)). A possible mechanism of formation of phase mixtures and morphology of copper oxides has also been discussed, which opens up a roadmap in synthesis of similar morphology nanostructures for efficient solar cells. PMID:24777390

  11. Development of second-generation small-molecule RhoA inhibitors with enhanced water solubility, tissue potency, and significant in vivo efficacy.

    PubMed

    Ma, Sheng; Deng, Jing; Li, Baoli; Li, Xiujiang; Yan, Zhaowei; Zhu, Jin; Chen, Gang; Wang, Zhong; Jiang, Hualiang; Miao, Liyan; Li, Jian

    2015-01-01

    RhoA, a member of the Rho GTPases, is involved in a variety of cellular functions and could be a suitable therapeutic target for the treatment of cardiovascular diseases. However, few small-molecule RhoA inhibitors have been reported. Based on our previously reported lead compounds, 32 new 2-substituted quinoline (or quinoxaline) derivatives were synthesized and tested in biological assays. Six compounds showed high RhoA inhibitory activities, with IC50 values of 1.17-1.84 μM. Among these, (E)-3-(3-(ethyl(quinolin-2-yl)amino)phenyl)acrylic acid (26 b) and (E)-3-(3-(butyl(quinolin-2-yl)amino)phenyl)acrylic acid (26 d) demonstrated noticeable vasorelaxation effects against phenylephrine-induced contraction in thoracic aorta artery rings, and compound 26 b had good water solubility and showed significant in vivo efficacy, which was similar to that of 5-(1,4-diazepane-1-sulfonyl)isoquinoline (fasudil) in a subarachnoid hemorrhage-cardiovascular model. To the best of our knowledge, compound 26 b is the first example of a small- molecule RhoA inhibitor with potent in vivo efficacy, which could serve as a good lead for designing cardiovascular agents. PMID:25377276

  12. Significant enhancement of methionol production by co-expression of the aminotransferase gene ARO8 and the decarboxylase gene ARO10 in Saccharomyces cerevisiae.

    PubMed

    Yin, Sheng; Lang, Tiandan; Xiao, Xiao; Liu, Li; Sun, Baoguo; Wang, Chengtao

    2015-03-01

    Methionol is an important volatile sulfur flavor compound, which can be produced via the Ehrlich pathway in Saccharomyces cerevisiae. Aminotransferase and decarboxylase are essential enzymes catalyzing methionol biosynthesis. In this work, two aminotransferase genes ARO8 and ARO9 and one decarboxylase gene ARO10 were introduced into S. cerevisiae S288c, respectively, via an expression vector. Over-expression of ARO8 resulted in higher aminotransferase activity than that of ARO9. And the cellular decarboxylase activity was remarkably increased by over-expression of ARO10. A co-expression vector carrying both ARO8 and ARO10 was further constructed to generate the recombinant strain S810. Shaking flask experiments showed that the methionol yield from S810 reached 1.27 g L(-1), which was increased by 51.8 and 68.8% compared to that from the wild-type strain and the control strain harboring the empty vector. The fed-batch fermentation by strain S810 produced 3.24 g L(-1) of methionol after 72 h of cultivation in a bioreactor. These results demonstrated that co-expression of ARO8 and ARO10 significantly boosted the methionol production. It is the first time that more than 3.0 g L(-1) of methionol produced by genetically engineered yeast strain was reported by co-expression of the aminotransferase and decarboxylase via the Ehrlich pathway. PMID:25743068

  13. Significant degradability enhancement in multilayer coating of polycaprolactone-bioactive glass/gelatin-bioactive glass on magnesium scaffold for tissue engineering applications

    NASA Astrophysics Data System (ADS)

    Yazdimamaghani, Mostafa; Razavi, Mehdi; Vashaee, Daryoosh; Pothineni, Venkata Raveendra; Rajadas, Jayakumar; Tayebi, Lobat

    2015-05-01

    Magnesium (Mg) is a promising candidate to be used in medical products especially as bone tissue engineering scaffolds. The main challenge for using Mg in biomedical applications is its high degradation rate in the body. For this reason, in this study, a multilayer polymeric layer composed of polycaprolactone (PCL) and gelatin (Gel) reinforced with bioactive glass (BaG) particles has been applied on the surface of Mg scaffolds. The materials characteristics of uncoated Mg scaffold, Mg scaffold coated only with PCL-BaG and Mg scaffold coated with PCL-BaG and Gel-BaG have been analyzed and compared in detail. Scanning electron microscope (SEM) equipped with energy dispersive spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR) were utilized for microstructural studies. In vitro bioactivity and biodegradation evaluations were carried out by submerging the scaffolds in simulated body fluid (SBF) at pre-determined time points. The results demonstrated that Mg scaffold coated with PCL-BaG and Gel-BaG exhibited significant improvement in biodegradability.

  14. Double mutation of Saccharomyces cerevisiae for enhanced β-d-fructofuranosidase fructohydrolase productivity and application of growth kinetics for parametric significance analysis

    PubMed Central

    Ali, Sikander; Aslam, Aafia; Hayyat, Muhammad Umar

    2016-01-01

    The kinetics of an extracellular β-d-fructofuranosidase fructohydrolase production by Saccharomyces cerevisiae in a chemically defined medium, i.e., sucrose peptone agar yeast extract at pH 6, was investigated. The wild-type was treated with a chemical mutagen, methyl methane sulfonate. Among the six mutants isolated, methyl methane sulfonate-V was found to be a better enzyme producing strain (52 ± 2.4a U/mL). The maximum production (74 ± 3.1a U/mL) was accomplished after at 48 h (68 ± 2.7a mg/mL protein). The mutants were stabilized at low levels of 5-fluoro-cytocine and the viable ones were further processed for optimization of cultural conditions and nutritional requirements. The sucrose concentration, incubation period and pH were optimized to be 30 g/L, 28 °C, and 6.5, respectively. The methyl methane sulfonate-V exhibited an improvement of over 10 folds in enzyme production when 5 g/L ammonium sulfate was used as a nitrogen source. Thin layer chromatography and high-performance liquid chromatography analysis illustrated the optimal enzyme activity supported by the higher rate of hydrolysis of sucrose into monosaccharides, particularly α-d-glucose and β-d-fructose. The values for Qp (2 ± 0.12c U/mL/h) and Yp/s (4 ± 1.24b U/g) of the mutant were considerably increased in comparison with other yeast strains (both isolates and viable mutants). The mutant could be exploited for enzyme production over a wider temperature range (26–34 °C), with significantly high enzyme activity (LSD 0.048, HS) at the optimal temperature. PMID:26887236

  15. Double mutation of Saccharomyces cerevisiae for enhanced β-d-fructofuranosidase fructohydrolase productivity and application of growth kinetics for parametric significance analysis.

    PubMed

    Ali, Sikander; Aslam, Aafia; Hayyat, Muhammad Umar

    2016-01-01

    The kinetics of an extracellular β-d-fructofuranosidase fructohydrolase production by Saccharomyces cerevisiae in a chemically defined medium, i.e., sucrose peptone agar yeast extract at pH 6, was investigated. The wild-type was treated with a chemical mutagen, methyl methane sulfonate. Among the six mutants isolated, methyl methane sulfonate-V was found to be a better enzyme producing strain (52±2.4(a)U/mL). The maximum production (74±3.1(a)U/mL) was accomplished after at 48h (68±2.7(a)mg/mL protein). The mutants were stabilized at low levels of 5-fluoro-cytocine and the viable ones were further processed for optimization of cultural conditions and nutritional requirements. The sucrose concentration, incubation period and pH were optimized to be 30g/L, 28°C, and 6.5, respectively. The methyl methane sulfonate-V exhibited an improvement of over 10 folds in enzyme production when 5g/L ammonium sulfate was used as a nitrogen source. Thin layer chromatography and high-performance liquid chromatography analysis illustrated the optimal enzyme activity supported by the higher rate of hydrolysis of sucrose into monosaccharides, particularly α-d-glucose and β-d-fructose. The values for Qp (2±0.12(c)U/mL/h) and Yp/s (4±1.24(b)U/g) of the mutant were considerably increased in comparison with other yeast strains (both isolates and viable mutants). The mutant could be exploited for enzyme production over a wider temperature range (26-34°C), with significantly high enzyme activity (LSD 0.048, HS) at the optimal temperature. PMID:26887236

  16. Reducing Human-Tsetse Contact Significantly Enhances the Efficacy of Sleeping Sickness Active Screening Campaigns: A Promising Result in the Context of Elimination

    PubMed Central

    Courtin, Fabrice; Camara, Mamadou; Rayaisse, Jean-Baptiste; Kagbadouno, Moise; Dama, Emilie; Camara, Oumou; Traoré, Ibrahima S.; Rouamba, Jérémi; Peylhard, Moana; Somda, Martin B.; Leno, Mamadou; Lehane, Mike J.; Torr, Steve J.; Solano, Philippe; Jamonneau, Vincent; Bucheton, Bruno

    2015-01-01

    Background Control of gambiense sleeping sickness, a neglected tropical disease targeted for elimination by 2020, relies mainly on mass screening of populations at risk and treatment of cases. This strategy is however challenged by the existence of undetected reservoirs of parasites that contribute to the maintenance of transmission. In this study, performed in the Boffa disease focus of Guinea, we evaluated the value of adding vector control to medical surveys and measured its impact on disease burden. Methods The focus was divided into two parts (screen and treat in the western part; screen and treat plus vector control in the eastern part) separated by the Rio Pongo river. Population census and baseline entomological data were collected from the entire focus at the beginning of the study and insecticide impregnated targets were deployed on the eastern bank only. Medical surveys were performed in both areas in 2012 and 2013. Findings In the vector control area, there was an 80% decrease in tsetse density, resulting in a significant decrease of human tsetse contacts, and a decrease of disease prevalence (from 0.3% to 0.1%; p=0.01), and an almost nil incidence of new infections (<0.1%). In contrast, incidence was 10 times higher in the area without vector control (>1%, p<0.0001) with a disease prevalence increasing slightly (from 0.5 to 0.7%, p=0.34). Interpretation Combining medical and vector control was decisive in reducing T. b. gambiense transmission and in speeding up progress towards elimination. Similar strategies could be applied in other foci. PMID:26267667

  17. Synergy of TLR3 and 7 ligands significantly enhances function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway.

    PubMed

    Hu, Yue; Cong, Xiaoyan; Chen, Lei; Qi, Jing; Wu, Xiangju; Zhou, Mingming; Yoo, Dongwan; Li, Feng; Sun, Wenbo; Wu, Jiaqiang; Zhao, Xiaomin; Chen, Zhi; Yu, Jiang; Du, Yijun; Wang, Jinbao

    2016-01-01

    PRRS is one of the most important diseases in swine industry. Current PRRS inactivated vaccine provides only a limited protection and cannot induce sufficient cell-mediated immune responses. In this study, we first found that the mRNA and protein levels of Th1-type cytokines (IFN-γ, IL-12) and Th2-type cytokines (IL-6, IL-10) were significantly increased through TRIF/MyD88-NF-κB signaling pathway when porcine peripheral blood monocyte-derived dendritic cells (MoDCs) were treated with poly (I: C) of TLR3 ligand and imiquimod of TLR7 ligand, along with inactivated PRRSV antigen. Meanwhile, the ability of catching PRRSV antigen was also significantly enhanced. In mice experiment, it was found that the PRRSV-specific T lymphocyte proliferation, the percentages of CD4(+), CD8(+) T lymphocytes and PRRSV-specific CD3(+) T cells producing IFN-γ and IL-4, the levels of Th1- and Th2-type cytokines and the titers of neutralization antibody were significantly enhanced in poly (I: C), imiquimod along with inactivated PRRSV group. Taken together, results of our experiments described for the first time that synergy of TLR3 and 7 ligands could significantly enhance the function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway and be used as adjuvant candidate for the development of novel PRRS inactivated vaccine. PMID:27046485

  18. Synergy of TLR3 and 7 ligands significantly enhances function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway

    PubMed Central

    Hu, Yue; Cong, Xiaoyan; Chen, Lei; Qi, Jing; Wu, Xiangju; Zhou, Mingming; Yoo, Dongwan; Li, Feng; Sun, Wenbo; Wu, Jiaqiang; Zhao, Xiaomin; Chen, Zhi; Yu, Jiang; Du, Yijun; Wang, Jinbao

    2016-01-01

    PRRS is one of the most important diseases in swine industry. Current PRRS inactivated vaccine provides only a limited protection and cannot induce sufficient cell-mediated immune responses. In this study, we first found that the mRNA and protein levels of Th1-type cytokines (IFN-γ, IL-12) and Th2-type cytokines (IL-6, IL-10) were significantly increased through TRIF/MyD88-NF-κB signaling pathway when porcine peripheral blood monocyte-derived dendritic cells (MoDCs) were treated with poly (I: C) of TLR3 ligand and imiquimod of TLR7 ligand, along with inactivated PRRSV antigen. Meanwhile, the ability of catching PRRSV antigen was also significantly enhanced. In mice experiment, it was found that the PRRSV-specific T lymphocyte proliferation, the percentages of CD4+, CD8+ T lymphocytes and PRRSV-specific CD3+ T cells producing IFN-γ and IL-4, the levels of Th1- and Th2-type cytokines and the titers of neutralization antibody were significantly enhanced in poly (I: C), imiquimod along with inactivated PRRSV group. Taken together, results of our experiments described for the first time that synergy of TLR3 and 7 ligands could significantly enhance the function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway and be used as adjuvant candidate for the development of novel PRRS inactivated vaccine. PMID:27046485

  19. Modernizing Administration.

    ERIC Educational Resources Information Center

    Lombardi, Vincent L.; Hildebrand, Verna

    1981-01-01

    Suggests assignment of research duties and rotation of teaching and management roles for college administrators, to increase their effectiveness and diminish the negative effects of declining enrollments. (JD)

  20. Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration.

    PubMed

    Han, Xiaofeng; Wang, Zhe; Wang, Manyuan; Li, Jing; Xu, Yongsong; He, Rui; Guan, Hongyu; Yue, Zhujun; Gong, Muxin

    2016-06-01

    In order to enhance oral bioavailability and liver targeting delivery of silybin, two amphiphilic hyaluronic acid derivatives, hyaluronic acid-deoxycholic acid (HA-adh-DOCA) and hyaluronic acid-glycyrrhetinic acid (HA-adh-GA) conjugates, were designed and synthesized. Silybin was successfully loaded in HA-adh-DOCA and HA-adh-GA micelles with high drug-loading capacities (20.3% ± 0.5% and 20.6% ± 0.6%, respectively). The silybin-loaded micelles were spherical in shape with the average size around 130 nm. In vitro release study showed that two silybin-loaded micelles displayed similar steady continued-release pattern in simulated gastrointestinal fluids and PBS. Single-pass intestinal perfusion studies indicated that silybin-loaded micelles were absorbed in the whole intestine and transported via a passive diffusion mechanism. Compared with suspension formulation, silybin-loaded HA-adh-DOCA and HA-adh-GA micelles achieved significantly higher AUC and Cmax level. Moreover, liver targeting drug delivery of micelles was confirmed by in vivo imaging analysis. In comparison between the two micellar formulations, HA-adh-GA micelles possessed higher targeting capacity than HA-adh-DOCA micelles, owing to the active hepatic targeting properties of glycyrrhetinic acid. In the treatment of acute liver injury induced by CCl4, silybin-loaded HA-adh-GA micelles displayed better effects over suspension control and silybin-loaded HA-adh-DOCA micelles. Overall, pharmaceutical and pharmacological indicators suggested that the HA-adh-GA conjugates can be successfully utilized for liver targeting of orally administered therapeutics. PMID:26556526

  1. Adenoviral gene transfer into the normal and injured spinal cord: enhanced transgene stability by combined administration of temperature-sensitive virus and transient immune blockade.

    PubMed

    Romero, M I; Smith, G M

    1998-12-01

    This study characterized gene transfer into both normal and injured adult rat dorsal spinal cord using first (E1-/E3-) or second (E1-/E2A125/E3-, temperature-sensitive; ts) generation of replication-defective adenoviral (Ad) vectors. A novel immunosuppressive regimen aimed at blocking CD4/CD45 lymphocytic receptors was tested for improving transgene persistence. In addition, the effect of gene transfer on nociception was also evaluated. Seven days after treatment, numerous LacZ-positive cells were observed after transfection with either viral vector. By 21 days after transfection, beta-galactosidase staining was reduced and suggestive of ongoing cytopathology in both Ad-treated groups, despite the fact that the immunogenicity of LacZ/Adts appeared less when compared with that elicited by the LacZ/Ad vector. In contrast, immunosuppressed animals showed a significant (P < or = 0.05) increase in the number of LacZ-positive cells not displaying cytopathology. In these animals, a concomitant reduction in numbers of macrophages/microglia and CD4 and CD8 lymphocytes was observed. Only animals that received LacZ/Adts and immunosuppression showed transgene expression after 60 days. Similar results were observed in animals in which the L4-L5 dorsal roots were lesioned before transfection. Gene transfer into the dorsal spinal cord did not affect nociception, independent of the adenovirus vector. These results indicate that immune blockade of the CD4/CD45 lymphocytic receptors enhanced transgene stability in adult animals with normal or injured spinal cords and that persistent transgene expression in the spinal cord does not interfere with normal neural function. PMID:10023440

  2. Administrative Support.

    ERIC Educational Resources Information Center

    Doran, Dorothy; And Others

    This guide is intended to assist business education teachers in administrative support courses. The materials presented are based on the Arizona validated occupational competencies and tasks for the occupations of receptionist, secretary, and administrative assistant. Word processing skills have been infused into each of the three sections. The…

  3. Administrative Ecology

    ERIC Educational Resources Information Center

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  4. Co-administration of plasmid expressing IL-12 with 14-kDa Schistosoma mansoni fatty acid-binding protein cDNA alters immune response profiles and fails to enhance protection induced by Sm14 DNA vaccine alone.

    PubMed

    Fonseca, Cristina T; Pacífico, Lucila G G; Barsante, Michele M; Rassi, Tatiana; Cassali, Geovanni D; Oliveira, Sérgio C

    2006-08-01

    Schistosomiasis is an endemic disease that affects 200 million people worldwide. DNA-based vaccine is a promising strategy to induce protective immunity against schistosomiasis, since both humoral and cellular immune responses are involved in parasite elimination. In this study, we evaluated the ability of Sm14 cDNA alone or in association with a plasmid expressing murine interleukin (IL)-12 to induce protection against challenge infection. Mice were immunized with four doses of the DNA vaccine and the levels of protection were determined by worm burden recovery after challenge infection. Specific antibody production to rSm14 was determined by ELISA, and cytokine production was measured in splenocyte culture supernatants stimulated with rSm14 and in bronchoalveolar lavage of vaccinated mice after challenge infection. DNA immunization with pCI/Sm14 alone induced 40.5% of worm reduction. However, the use of pCI/IL-12 as adjuvant to pCI/Sm14 immunization failed to enhance protection against challenge infection. Protection induced by pCI/Sm14 immunization correlates with specific IgG antibody production against Sm14, Th1 type of immune response with high levels of interferon (IFN)-gamma and low levels of IL-4 in splenocyte culture supernatants and in bronchoalveolar lavage after challenge infection. IL-12 co-administration with pCI/Sm14 induced a significant production of nitric oxide in splenocyte culture supernatants and also lymphocyte suppression, with reduced percentage of T cells producing IFN-gamma and tumor necrosis factor-alpha. PMID:16914349

  5. Symbiotic structures to significantly enhance space missions

    NASA Astrophysics Data System (ADS)

    Williams, Andrew D.; Diaz-Aguado, Millan; Arritt, Brandon J.

    2007-04-01

    The Department of Defense is actively pursuing a Responsive Space capability that will dramatically reduce the cost and time associated with getting a payload into space. In order to enable that capability, our space systems must be modular and flexible to cover a wide range of missions, configurations, duty cycles, and orbits. This places requirements on the entire satellite infrastructure: payloads, avionics, electrical harnessing, structure, thermal management system, etc. The Integrated Structural Systems Team at the Air Force Research Laboratory, Space Vehicles Directorate, has been tasked with developing structural and thermal solutions that will enable a Responsive Space capability. This paper details a "symbiotic" solution where thermal management functionality is embedded within the structure of the satellite. This approach is based on the flight proven and structurally efficient isogrid architecture. In our rendition, the ribs serve as fluidic passages for thermal management, and passively activated valves are used to control flow to the individual components. As the paper will explain, our analysis has shown this design to be structurally efficient and thermally responsive to a wide range of potential satellite missions, payloads, configurations, and orbits.

  6. Dietary administration of Gynura bicolor (Roxb. Willd.) DC water extract enhances immune response and survival rate against Vibrio alginolyticus and white spot syndrome virus in white shrimp Litopeneaus vannamei.

    PubMed

    Wu, Chih-Chung; Chang, Yueh-Ping; Wang, Jyh-Jye; Liu, Chun-Hung; Wong, Saou-Lien; Jiang, Chii-Ming; Hsieh, Shu-Ling

    2015-01-01

    Gynura bicolor (Roxb. & Willd.) DC., a perennial plant belonging to the Asteraceae family, is originated from the tropical area of Asia. The total hemocyte count (THC), phenoloxidase (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) activity, and lysozyme activity were examined after white shrimp Litopenaeus vannamei had been fed diets containing the water extract of G. bicolor at 0 (control), 0.5, 1.0, and 2.0 g (kg diet)(-1) for 7-28 days. The results indicated that these parameters increased accordingly with the amount of extract and time. THCs of the shrimp fed the G. bicolor diets at 1.0 and 2.0 g (kg diet)(-1) were significantly higher than that fed the control diet for 14-28 days. For the shrimp fed the G. bicolor diets at 0.5, 1.0, and 2.0 g (kg diet)(-1), the PO, RBs, and lysozyme activities reached the highest levels after 7 days, whereas SOD activity reached the highest levels after 14 days. In a separate experiment, white shrimp L. vannamei fed the diets containing the G. bicolor extract for 28 days were challenged with Vibrio alginolyticus at 3 × 10(6) cfu shrimp(-1) and white spot syndrome virus (WSSV) at 1 × 10(3) copies shrimp(-1). The survival rate of the shrimp fed the G. bicolor diets was significantly higher than that of the shrimp fed the control diet at 48-144 h post challenge V. alginolyticus and WSSV. For the shrimp fed the G. bicolor diets at 0.5, 1 and 2 g (kg diet)(-1) under challenges of V. alginolyticus and WSSV, their LPS- and β-1,3-glucan-binding protein (LGBP) and peroxinectin (PE) mRNA expressions were significantly higher than those of the challenged control shrimp at 12-96 and 24-144 h post-challenge, respectively. We concluded that dietary administration of a G. bicolor extract could enhance the innate immunity within 28 days as evidenced by the increases in immune parameters (PO, RBs, and lysozyme) and antioxidant enzyme (SOD) activities of shrimp to against V. alginolyticus and WSSV

  7. Chronic L-DOPA administration increases the firing rate but does not reverse enhanced slow frequency oscillatory activity and synchronization in substantia nigra pars reticulata neurons from 6-hydroxydopamine-lesioned rats.

    PubMed

    Aristieta, A; Ruiz-Ortega, J A; Miguelez, C; Morera-Herreras, T; Ugedo, L

    2016-05-01

    The pathophysiology of Parkinson's disease (PD) and of L-DOPA-induced dyskinesia (LID) is associated with dysfunctional neuronal activity in several nuclei of the basal ganglia. Moreover, high levels of oscillatory activity and synchronization have also been described in both intra- and inter-basal ganglia nuclei and the cerebral cortex. However, the relevance of these alterations in the motor symptomatology related to Parkinsonism and LID is not fully understood. Recently, we have shown that subthalamic neuronal activity correlates with axial abnormal movements and that a subthalamic nucleus (STN) lesion partially reduces LID severity as well as the expression of some striatal molecular modifications. The aim of the present study was to assess, through single-unit extracellular recording techniques under urethane anaesthesia, neuronal activity of the substantia nigra pars reticulata (SNr) and its relationship with LID and STN hyperactivity together with oscillatory and synchronization between these nuclei and the cerebral cortex in 6-OHDA-lesioned and dyskinetic rats. Twenty-four hours after the last injection of L-DOPA the firing rate and the inhibitory response to an acute challenge of L-DOPA of SNr neurons from dyskinetic animals were increased with respect to those found in intact and 6-OHDA-lesioned rats. Moreover, there was a significant correlation between the mean firing rate of SNr neurons and the severity of the abnormal movements (limb and orolingual subtypes). There was also a significant correlation between the firing activity of SNr and STN neurons recorded from dyskinetic rats. In addition, low frequency band oscillatory activity and synchronization both within the SNr or STN and with the cerebral cortex were enhanced in 6-OHDA-lesioned animals and not or slightly affected by chronic treatment with L-DOPA. Altogether, these results indicate that neuronal SNr firing activity is relevant in dyskinesia and may be driven by STN hyperactivity. Conversely

  8. Differences in Anxiety-Like Behavior within a Batch of Wistar Rats Are Associated with Differences in Serotonergic Transmission, Enhanced by Acute SRI Administration, and Abolished By Serotonin Depletion

    PubMed Central

    Näslund, Jakob; Studer, Erik; Pettersson, Robert; Hagsäter, Melker; Nilsson, Staffan; Nissbrandt, Hans

    2015-01-01

    Background: The anxiety-reducing effect of long-term administration of serotonin reuptake inhibitors is usually seen only in subjects with anxiety disorders, and such patients are also abnormally inclined to experience a paradoxical anxiety-enhancing effect of acute serotonin reuptake inhibition. These unique responses to serotonin reuptake inhibitors in anxiety-prone subjects suggest, as do genetic association studies, that inter-individual differences in anxiety may be associated with differences in serotonergic transmission. Methods: The one-third of the animals within a batch of Wistar rats most inclined to spend time on open arms in the elevated plus maze were compared with the one-third most inclined to avoid them with respect to indices of brain serotonergic transmission and how their behavior was influenced by serotonin-modulating drugs. Results: “Anxious” rats displayed higher expression of the tryptophan hydroxylase-2 gene and higher levels of the tryptophan hydroxylase-2 protein in raphe and also higher levels of serotonin in amygdala. Supporting these differences to be important for the behavioral differences, serotonin depletion obtained by the tryptophan hydroxylase-2 inhibitor p-chlorophenylalanine eliminated them by reducing anxiety in “anxious” but not “non-anxious” rats. Acute administration of a serotonin reuptake inhibitor, paroxetine, exerted an anxiety-enhancing effect in “anxious” but not “non-anxious” rats, which was eliminated by long-term pretreatment with another serotonin reuptake inhibitor, escitalopram. Conclusions: Differences in an anxiogenic impact of serotonin, which is enhanced by acute serotonin reuptake inhibitor administration, may contribute to differences in anxiety-like behavior amongst Wistar rats. PMID:25716782

  9. The tumor protection effect of high-frequency administration of whole tumor cell vaccine and enhanced efficacy by the protein component from Agrocybe aegerita

    PubMed Central

    Liang, Yi; Sun, Hui

    2015-01-01

    Whole tumor cell vaccines have been widely studied and elicits limited immune responses because of the poor immunogenicity. In the present study, we discovered that high-frequency administration of irradiated whole tumor cell vaccine triggered rejection of tumor cells (90% or 100% of the mice that were vaccinated with irradiated H22 cells or S180 respectively were protected), and provided cross-protection and long-term anti-tumor immunity in BALB/c mouse models. The antitumor activity required CD4+, CD8+ T cells and macrophage that was proved in the nude mice and cell depletion mouse models. The adoptive transfer experiment suggested that repeated whole tumor cell vaccination successfully stimulated the anti-tumor response by activation of the immune cells. A high immunization frequency within a short period of time and the presence of glycosylated molecules and nucleic acids on the surface of intact tumor cells were crucial for the successful prevention of tumor growth by whole tumor cell vaccines. Moreover, Yt, the protein component from fungus Agrocybe aegerita, increased whole tumor cell vaccine-mediated tumor rejection and cross-protection effect. These data indicated that the frequency of administration of whole tumor cell vaccines was of critical importance for the efficacy, which needed to be integrated into vaccine strategies for producing potential vaccines. PMID:26221228

  10. Significantly enhanced ferroelectricity and magnetic properties in (Sr{sub 0.5}Ca{sub 0.5})TiO{sub 3}-modified BiFeO{sub 3} ceramics

    SciTech Connect

    Liu, Juan; Liu, Xiao Qiang E-mail: xmchen59@zju.edu.cn; Chen, Xiang Ming E-mail: xmchen59@zju.edu.cn

    2015-05-07

    BiFeO{sub 3} multiferroic ceramics were modified by introducing (Sr{sub 0.5}Ca{sub 0.5})TiO{sub 3} to form solid solutions. The single phase structure was easy to be obtained in Bi{sub 1−x}(Sr{sub 0.5}Ca{sub 0.5}){sub x}Fe{sub 1−x}Ti{sub x}O{sub 3} (x = 0.2, 0.25, 0.3, and 0.4) solid solutions. Rietveld refinement of X-ray diffraction data revealed a transition from rhombohedral R3c (x = 0.2, 0.25, and 0.3) to orthorhombic Pnma (x = 0.4). Current density-field (J-E) characteristics indicated that the leakage current density was reduced by three orders of magnitude in Bi{sub 1−x}(Sr{sub 0.5}Ca{sub 0.5}){sub x}Fe{sub 1−x}Ti{sub x}O{sub 3} ceramics. Both the ferroelectricity and magnetic properties were significantly enhanced in the present solid solutions. P-E hysteresis loop measurements with dynamic leakage current compensation methods showed the significantly enhanced ferroelectric properties for x = 0.25 and 0.3 and the paraelectric behavior for x = 0.4. The best ferromagnetic characteristics were achieved in the composition of x = 0.25, where the saturated M-H loop was determined with M{sub r} = 34.8 emu/mol. The improvement of ferroelectricity was mainly due to the suppressed leakage current, and the enhanced magnetism originated from the partial substitution of Fe{sup 3+} by Ti{sup 4+}, which destroyed its previous spiral structure to allow the appearance of a macroscopic magnetization.

  11. Administrative IT

    ERIC Educational Resources Information Center

    Grayson, Katherine, Ed.

    2006-01-01

    When it comes to Administrative IT solutions and processes, best practices range across the spectrum. Enterprise resource planning (ERP), student information systems (SIS), and tech support are prominent and continuing areas of focus. But widespread change can also be accomplished via the implementation of campuswide document imaging and sharing,…

  12. Engineering Administration.

    ERIC Educational Resources Information Center

    Naval Personnel Program Support Activity, Washington, DC.

    This book is intended to acquaint naval engineering officers with their duties in the engineering department. Standard shipboard organizations are analyzed in connection with personnel assignments, division operations, and watch systems. Detailed descriptions are included for the administration of directives, ship's bills, damage control, training…

  13. ADMINISTRATIVE CLIMATE.

    ERIC Educational Resources Information Center

    BRUCE, ROBERT L.; CARTER, G.L., JR.

    IN THE COOPERATIVE EXTENSION SERVICE, STYLES OF LEADERSHIP PROFOUNDLY AFFECT THE QUALITY OF THE SERVICE RENDERED. ACCORDINGLY, MAJOR INFLUENCES ON ADMINISTRATIVE CLIMATE AND EMPLOYEE PRODUCTIVITY ARE EXAMINED IN ESSAYS ON (1) SOURCES OF JOB SATISFACTION AND DISSATISFACTION, (2) MOTIVATIONAL THEORIES BASED ON JOB-RELATED SATISFACTIONS AND NEEDS,…

  14. Database Administrator

    ERIC Educational Resources Information Center

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  15. Co-administration of CpG oligonucleotides enhances the late affinity maturation process of human anti-hepatitis B vaccine response.

    PubMed

    Siegrist, Claire-Anne; Pihlgren, Maria; Tougne, Chantal; Efler, Sue M; Morris, Mary Lou; AlAdhami, Mohammed J; Cameron, D William; Cooper, Curtis L; Heathcote, Jenny; Davis, Heather L; Lambert, Paul-Henri

    2004-12-16

    We assessed the avidity maturation process elicited by human immunization with alum-adsorbed HBsAg alone or with a novel adjuvant containing CpG motifs (CpG 7909). Mean avidity indexes and distribution of low- and high-avidity anti-HBs indicated that avidity maturation essentially takes place late after priming. CpG 7909 markedly enhanced this affinity maturation process, increasing the pool of high-avidity antibodies. The influence of CpG 7909 was antigen-specific, isotype-specific and distinct from the influence on anti-HBs production, as avidity did not correlate with anti-HBs IgG titers. This is the first demonstration that a novel human adjuvant may induce antibodies with higher antigen-binding affinity. PMID:15542181

  16. Co-Administration of Poly I:C and ISCOMs Modifies Antigen Processing in Dendritic Cell Subsets and Enhances HIV Gag-Specific T Cell Immunity

    PubMed Central

    Quinn, Kylie M.; Yamamoto, Ayako; Costa, Andreia; Darrah, Patricia A.; Lindsay, Ross W.B.; Hegde, Sonia T.; Johnson, Teresa R.; Flynn, Barbara J.; Lore, Karin; Seder, Robert A.

    2013-01-01

    Currently approved adjuvants induce protective antibody responses but are more limited for generating cellular immunity. Here we assessed the effect of combining two adjuvants with distinct mechanisms of action on their ability to prime T cells; the TLR3 ligand, polyinosinic:polycytidylic acid (Poly I:C), and immunostimulatory complexes (ISCOMs). Each adjuvant was administered alone or together with HIV Gag protein (Gag) and the magnitude, quality and phenotype of Gag-specific T cell responses were assessed. For CD8 T cells, all adjuvants induced a comparable response magnitude, but combining Poly I:C with ISCOMs induced a high frequency of CD127+, IL-2 producing cells with decreased expression of Tbet compared to either adjuvant alone. For CD4 T cells, combining Poly I:C and ISCOMs increased the frequency of multifunctional cells, producing IFNγ, IL-2 and TNF, and the total magnitude of the response compared to either adjuvant alone. CD8 or CD4 T cell responses induced by both adjuvants mediated protection against Gag-expressing Listeria monocytogenes or vaccinia viral infections. Poly I:C and ISCOMs can alter antigen uptake and/or processing and we therefore used fluorescently labeled HIV Gag and DQ-OVA to assess these mechanisms respectively in multiple DC subsets. Poly I:C promoted uptake and retention of antigen, while ISCOMs enhanced antigen degradation. Combining Poly I:C and ISCOMs caused substantial death of DCs but persistence of degraded antigen. These data illustrate how combining adjuvants, such as Poly I:C and ISCOMs that modulate antigen processing and have potent innate activity, can enhance the magnitude, quality and phenotype of T cell immunity. PMID:24089189

  17. A Change of Administration: A Significant Organizational Life Event.

    ERIC Educational Resources Information Center

    Stine, Deborah E.

    The case study presented in this paper illustrates how the succession process for principals is similar to that described by Gabarro in his study of corporate succession. Leader succession involves five major stages: (1) taking hold; (2) immersion; (3) reshaping; (4) consolidation; and (5) refinement. Success most frequently occurs in conjunction…

  18. Pre-irradiation with low-dose 12C6+ beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

    NASA Astrophysics Data System (ADS)

    Liu, Bing; Zhang, Hong; Li, Wenjian; Li, Qiang; Zhou, Guangming; Xie, Yi; Hao, Jifang; Min, Fengling; Zhou, Qingming; Duan, Xin

    2007-04-01

    The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were significantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30% 60%, 20% 130% and 30% 70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

  19. Enhanced central serotonin release from slices of rat hypothalamus following repeated nialamide administration: evidence supporting the overactive serotonin receptor theory of depression

    SciTech Connect

    Offord, S.J.

    1986-01-01

    Researchers are suggesting unipolar affective disorders may be related to an abnormality in biogenic amine receptor-sensitivity. This abnormality may be a result of a dysfunction in central serotonin (5-HT) release mechanisms. 5-HT neurotransmission is modulated by presynaptic autoreceptors, which are members of the 5-HT/sub 1/ receptor subtype. The autoreceptor is thought to play an important role in the homeostasis of the central 5-HT synapse and could be a site at which some antidepressants mediate their therapeutic effect. The number of 5-HT/sub 1/ type receptor binding sites are reduced and behavior mediated by this receptor is abolished following repeated injections of monoamine oxidase inhibitor type antidepressants. These changes did not occur following a single injection. It was hypothesized that repeated treatment with a monoamine oxidase inhibitor would reduce the sensitivity of 5-HT autoreceptors and enhance 5-HT release. Rats were pretreated with single or repeated (twice daily for 7 days) intraperitoneal injections of nialamide (40 mg/kg) or chlorimipramine (10 mg/kg) and the ability of the autoreceptor agonist to inhibit potassium-induced /sup 3/H-5-HT release was evaluated using an in vitro superfusion system. These changes in 5-HT autoreceptor activity are consistent with other reports evaluating monoamine oxidase inhibitors on 5-HT/sub 1/ type receptors. It is hypothesized that the changes in 5-HT neurotransmission are related to the antidepressant mechanism of monoamine oxidase inhibitors.

  20. Oral administration recombinant porcine epidermal growth factor enhances the jejunal digestive enzyme genes expression and activity of early-weaned piglets.

    PubMed

    Lee, D N; Chuang, Y S; Chiou, H Y; Wu, F Y; Yen, H T; Weng, C F

    2008-08-01

    This study attempted to determine ingested porcine epidermal growth factor (pEGF) on the gastrointestinal tract development of early-weaned piglets. Thirty-two piglets (14-day weaned) were randomly allotted to supplemented with 0 (control), 0.5, 1.0, or 1.5 mg pEGF/kg diet. Each treatment consisted of four replicates with two pigs per pen for a 14 days experimental period. Piglets were sacrificed and gastrointestinal tract samples were collected to measure mucosa morphology, mRNA expression and activities of digestive enzymes in the gastrointestinal tract of piglets at the end of the experiment. Diets supplemented with pEGF failed to influence growth performance but tended to increase jejunal mucosa weight (p < 0.09) and protein content (p < 0.07). Piglets supplemental pEGF induced incrementally the gastric pepsin activity (p < 0.05) and stimulated jejunal alkaline phosphatase (ALP) and lactase activities accompanied with the increase of jejunal ALP and maltase mRNA expression. No effect of pEGF on the activities of all enzymes in ileum except the stimulation of ileal aminopeptide N mRNA expression. These results reveal that dietary pEGF supplementation might enhance gene expression and activities of digestive enzymes in the stomach and jejunum of piglets. PMID:18662356

  1. A Prime-Boost Strategy Combining Intravaginal and Intramuscular Administration of Homologous Adenovirus to Enhance Immune Response Against HIV-1 in Mice.

    PubMed

    Ji, Zhonghua; Xie, Zhaolu; Wang, Qin; Zhang, Zhirong; Gong, Tao; Sun, Xun

    2016-03-01

    Immune responses to HIV in the vaginal tract effectively trigger both systemic and mucosal protection, providing a double layer of defense. However, recombinant adenoviral (rAd) vectors delivered intravaginally do not effectively penetrate the mucus layer and vaginal epithelium, and instead are rapidly cleared. To overcome these barriers, we previously synthesized a novel cationic polyethylene glycol derivative that can self-assemble into nanocomplexes with rAd. These nanocomplexes can help rAd bypass the mucus layer and enhance mucosal immune response to the encoded antigen. However, the resulting cellular and humoral responses were still lower than those elicited by single intramuscular injection of rAd. Therefore, in the present study we investigated a new vaccination strategy involving intravaginal priming with our nanocomplexes, followed by an intramuscular boost with rAd-gag. Mice immunized in this way showed more potent humoral and cellular responses, as well as higher IgA levels, than animals primed and boosted intravaginally with nanocomplexes. These results show the promise of a prime-boost strategy for developing vaccine candidates against HIV. PMID:26715124

  2. CpG DNA facilitate the inactivated transmissible gastroenteritis virus in enhancing the local and systemic immune response of pigs via oral administration.

    PubMed

    Lin, Jian; Tu, Chongzhi; Mou, Chunxiao; Chen, Xiaojuan; Yang, Qian

    2016-04-01

    Transmissible gastroenteritis virus (TGEV) replicates in the small intestine and induces enteritis and watery diarrhea. Establishment of local immunity in the intestine would thus prevent TGEV transmission. CpG DNA has been reported as a promising mucosal adjuvant in some animals. The effects of oral immunization of CpG DNA together with inactivated TGEV (ITGEV) were investigated in this study. Pigs (6 weeks old) were orally immunized with ITGEV plus CpG DNA. The TGEV-specific IgA level in the intestinal tract and the TGEV-specific IgG level in serum significantly increased following immunization with ITGEV plus CpG DNA (P ≤ 0.05). Moreover, populations of IgA-secreting cells, CD3+ T lymphocytes and intraepithelial lymphocytes (IELs), in the intestine increased significantly after immunization with ITGEV plus CpG DNA (P ≤ 0.05). Furthermore, the expression of IL-6, IL-12 and interferon-γ (IFN-γ) in ligated intestine segments increased significantly after injection with ITGEV plus CpG DNA (P ≤ 0.05). Taken together, these data suggest that oral immunization of ITGEV plus CpG DNA elicits a local immune response. Further studies are required to determine whether this immunity provides protection against TGEV in pigs. PMID:27032496

  3. Administration of insulin to newly hatched chicks improves growth performance via impairment of MyoD gene expression and enhancement of cell proliferation in chicken myoblasts.

    PubMed

    Sato, Kan; Aoki, Michiru; Kondo, Ryota; Matsushita, Kohichi; Akiba, Yukio; Kamada, Tosihiko

    2012-02-01

    The insulin/PI3K/Akt signaling pathway is strongly involved in the differentiation of C2C12 cells, as has been demonstrated by the addition of IGFs and insulin to culture media. In this study, we have characterized the role of insulin in chick myoblast proliferation and differentiation in vitro and in vivo, and have revealed novel details of how this exogenous hormone influences myogenic genes during differentiation. Chick myoblast cells cultured in differentiation medium (DMEM containing 2% FBS) supplemented with insulin exhibited a significant decrease in MyoD and myogenin mRNA expression after 12h of culture compared to cells cultured in differentiation media alone. MyoD and myogenin immunoreactive proteins in cells cultured in differentiation medium supplemented with insulin were quite low compared to those in control culture. Supplementation of the differentiation media containing insulin with LY294002 (a PI3K inhibitor) induced myoblast differentiation. A significant increase in MyoD and myogenin mRNA expression was observed in these cells after incubation for 12h, and the level of expression was similar to that of control cells incubated with differentiation media alone. The DNA content and the phosphor-Erk1/2 protein level were increased by the addition of insulin to the differentiation medium. These results suggest that insulin and its signaling pathway play an inhibitory role in chick myoblast differentiation. A high level of Pax7 mRNA was observed in the skeletal muscle of 3-day-old chicks administered insulin or tolbutamide at 1-day-of-age. In addition, body weight at 21 and 50 days-of-age was significantly greater for chickens administered insulin or tolbutamide at 1-day-of-age than for control chickens. These results detail not only species-specific differences in insulin action for myoblasts but also provide novel information that may be used for the improvement of chicken meat production. PMID:22172340

  4. Administration of recombinant Reishi immunomodulatory protein (rLZ-8) diet enhances innate immune responses and elicits protection against nervous necrosis virus in grouper Epinephelus coioides.

    PubMed

    Kuan, Yen-Chou; Sheu, Fuu; Lee, Guo-Chi; Tsai, Ming-Wei; Hung, Chih-Liang; Nan, Fan-Hua

    2012-06-01

    Nervous necrosis virus (NNV) infection during larvae and juvenile stage in grouper (Epinephelus coioides) has caused severe economic losses in the aquaculture industry in Asia. The aims of this study were to evaluate the influence of recombinant Reishi protein, rLZ-8, on the innate immune responses and the viral resisting ability in fish. Groupers were fed with rLZ-8 supplemented diet (1.25-37.5 mg (rLZ-8)/kg(diet)), and the cytokine gene expression, innate immune responses, and survival rate after NNV challenge were examined. The fish fed with rLZ-8 diet showed 6- to 11-fold upregulated TNF-α and IL-1β gene expression, along with significant increased respiratory burst and phagocytic activity. Moreover, feeding the fish with 37.5 mg/kg rLZ-8 diet elicited significant improvement in post viral challenge survival rate (85.7%). These discoveries indicated that rLZ-8 could be utilized as an ant-pathogen immunostimulant, and provided a new candidate to fight against NNV infection in fish. PMID:22366063

  5. Credit Enhancement Overview Guide

    SciTech Connect

    Financing Solutions Working Group

    2014-01-01

    Provides considerations for state and local policymakers and energy efficiency program administrators designing and implementing successful credit enhancement strategies for residential and commercial buildings.

  6. Co-administration of avian influenza virus H5 plasmid DNA with chicken IL-15 and IL-18 enhanced chickens immune responses

    PubMed Central

    2012-01-01

    Background DNA vaccines offer several advantages over conventional vaccines in the development of effective vaccines against avian influenza virus (AIV). However, one of the limitations of the DNA vaccine in poultry is that it induces poor immune responses. In this study, chicken interleukin (IL) -15 and IL-18 were used as genetic adjuvants to improve the immune responses induced from the H5 DNA vaccination in chickens. The immunogenicity of the recombinant plasmid DNA was analyzed based on the antibody production, T cell responses and cytokine production, following inoculation in 1-day-old (Trial 1) and 14-day-old (Trial 2) specific-pathogen-free chickens. Hence, the purpose of the present study was to explore the role of chicken IL-15 and IL-18 as adjuvants following the vaccination of chickens with the H5 DNA vaccine. Results The overall HI antibody titer in chickens immunized with pDis/H5 + pDis/IL-15 was higher compared to chickens immunized with pDis/H5 (p < 0.05). The findings revealed that the inoculation of the 14-day-old chickens exhibited a shorter time to achieve the highest HI titer in comparison to the inoculation of the 1-day-old chickens. The cellular immunity was assessed by the flow cytometry analysis to enumerate CD4+ and CD8 + T cells in the peripheral blood. The chickens inoculated with pDis/H5 + pDis/IL-15 demonstrated the highest increase in CD4+ T cells population relative to the control chickens. However, this study revealed that pDis/H5 + pDis/IL-15 was not significant (P > 0.05) in inducing CD8+ T cells. Meanwhile, with the exception of Trial 1, the flow cytometry results for Trial 2 demonstrated that the pDis/H5 + pDis/IL-18 inoculated group was able to trigger a higher increase in CD4+ T cells than the pDis/H5 group (P < 0.05). On the other hand, the pDis/H5 + pDis/IL-18 group was not significant (P > 0.05) in modulating CD8+ T cells population in both trials. The pDis/H5 + pDis/IL-15 inoculated

  7. The use of hot and cold high pressure homogenization to enhance the loading capacity and encapsulation efficiency of nanostructured lipid carriers for the hydrophilic antiretroviral drug, didanosine for potential administration to paediatric patients.

    PubMed

    Kasongo, Kasongo Wa; Müller, Rainer H; Walker, Roderick B

    2012-01-01

    A major obstacle to the application of nanostructured lipid carriers (NLCs) as carriers for hydrophilic drugs is the limited loading capacity (LC) and encapsulation efficiency (EE) of NLCs for these molecules. The purpose of this research was to design and implement a strategy to enhance the LC and EE of NLCs for the hydrophilic drug, didanosine (DDI). DDI was dispersed in Transcutol(®) HP and the particle size of DDI in the liquid lipid was reduced gradually using hot high pressure homogenization (HPH). The product obtained thereafter was added to Precirol(®) ATO 5 and the hot mixture was immediately dried using liquid nitrogen. The dried materials were then ground and passed through a 200 μm sieve and the solid lipid particles were dispersed in a surfactant solution and subsequently used to manufacture DDI-loaded NLCs using cold HPH. The LC and EE of NLCs for DDI manufactured using the new strategy were 3.39 ± 0.63% and 51.58 ± 1.31%, respectively, compared to 0.079 ± 0.001% and 32.45 ± 0.08%, respectively, obtained when DDI-loaded NLCs were produced using conventional hot HPH. The enhanced LC and EE for DDI make NLCs a potential technology for the oral administration of DDI to paediatric patients. PMID:21241166

  8. A Microporous Metal-Organic Framework with Lewis Basic Nitrogen Sites for High C2H2 Storage and Significantly Enhanced C2H2/CO2 Separation at Ambient Conditions.

    PubMed

    Wen, Hui-Min; Wang, Huizhen; Li, Bin; Cui, Yuanjing; Wang, Hailong; Qian, Guodong; Chen, Banglin

    2016-08-01

    A novel metal-organic framework (MOF), [Cu2L(H2O)2]·7DMF·4H2O [ZJU-40; H4L = 5,5'-(pyrazine-2,5-diyl)diisophthalic acid], with Lewis basic nitrogen sites has been constructed and structurally characterized. Owing to the combined features of high porosity, moderate pore sizes, and immobilized Lewis basic nitrogen sites, the activated ZJU-40a exhibits the second-highest gravimetric C2H2 uptake of 216 cm(3) g(-1) (at 298 K and 1 bar) among all of the reported MOFs so far. This value is not only much higher than that of the isoreticular NOTT-101a (184 cm(3) g(-1)), but also superior to those of two very promising MOFs, known as HKUST-1 (201 cm(3) g(-1)) and Co-MOF-74 (197 cm(3) g(-1)). Interestingly, the immobilized nitrogen sites in ZJU-40a have nearly no effect on the CO2 uptake, so ZJU-40a adsorbs a similar amount of CO2 (87 cm(3) g(-1)) compared with NOTT-101a (84 cm(3) g(-1)) at 298 K and 1 bar. As a result, ZJU-40a shows significantly enhanced adsorption selectivity for C2H2/CO2 separation (17-11.5) at ambient temperature compared to that of NOTT-101a (8-9), leading to a superior MOF material for highly selective C2H2/CO2 separation. PMID:27176900

  9. Cognitive Enhancement and Education

    ERIC Educational Resources Information Center

    Buchanan, Allen

    2011-01-01

    Cognitive enhancement--augmenting normal cognitive capacities--is not new. Literacy, numeracy, computers, and the practices of science are all cognitive enhancements. Science is now making new cognitive enhancements possible. Biomedical cognitive enhancements (BCEs) include the administration of drugs, implants of genetically engineered or…

  10. Metallic MoO2 cocatalyst significantly enhances visible-light photocatalytic hydrogen production over MoO2/Zn0.5Cd0.5S heterojunction

    NASA Astrophysics Data System (ADS)

    Du, Hong; Xie, Xiao; Zhu, Qing; Lin, Ling; Jiang, Yi-Fan; Yang, Zheng-Kun; Zhou, Xiao; Xu, An-Wu

    2015-03-01

    As semiconductor-based nanoheterostructures play a decisive role in current electronics and optoelectronics, the introduction of active heterojunctions can afford new and improved capabilities that will enhance the conversion of solar energy into chemical energy. In this work, a novel metal/semiconductor MoO2/Zn0.5Cd0.5S heterojunction has been designed and prepared to significantly enhance photocatalytic H2 production efficiency. The photocatalytic activity of the as-prepared MoO2/Zn0.5Cd0.5S for H2 generation from water under visible-light irradiation (λ >= 420 nm) is measured. MoO2/Zn0.5Cd0.5S hybrid nanoparticles have a higher photocatalytic activity than Zn0.5Cd0.5S even without the noble metal cocatalyst. The results show that the rate of H2 evolution over annealed MoO2/Zn0.5Cd0.5S is about 13 times higher than that of Zn0.5Cd0.5S alone, and 10 times higher than that of simply mixed MoO2/Zn0.5Cd0.5S. Implying that the strong coupling at the interface of MoO2 and Zn0.5Cd0.5S facilitates electron transfer from the conduction band of Zn0.5Cd0.5S to metallic MoO2, thus promoting the separation of photogenerated electrons and holes. MoO2 (2 wt%)/Zn0.5Cd0.5S heterostructured photocatalyst calcined at 673 K achieves the optimal overall activity for H2 evolution. The introduction of metallic MoO2 cocatalyst leads to a remarkable improvement in the photo current and photocatalytic H2 production activity of Zn0.5Cd0.5S, and the content of MoO2 in this catalyst has an important influence on the photocatalytic activity. It is shown that 2 wt% metallic MoO2 loaded on Zn0.5Cd0.5S sample produces a maximum photocatalytic H2 production rate of 252.4 μmol h-1. The junctions formed between metallic MoO2 and semiconductor Zn0.5Cd0.5S by calcination play a key role in high photocatalytic water splitting to produce H2. Our study demonstrates that metallic MoO2 is an excellent H2 evolution cocatalyst, and could be used as a cocatalyst for other semiconductors to improve

  11. The Library Administrator's Automation Handbook.

    ERIC Educational Resources Information Center

    Boss, Richard W.

    One of the most significant decisions in a library administrator's career is the decision to automate one or more of a library's operations. This book describes the present state of local library automation; the planning, selection, and implementation process; and the library administrator's role in the process. The bulk of the text provides a…

  12. Enhancing Individual Readiness.

    ERIC Educational Resources Information Center

    1997

    This document contains three papers from a symposium on enhancing individual readiness through human resource development (HRD). "Secondary School Administrator's Perception of Enhancing Self-Worth through Service" (Thomas Li-Ping Tang, Emily James Weatherford) presents results of a study to examine secondary school administrators' endorsement of…

  13. Improving Administrative Efficiency through Technology.

    ERIC Educational Resources Information Center

    Porter, Dennis R.

    1993-01-01

    Key adult education management functions (planning, directing personnel, organizing work, staffing, and evaluating) can be enhanced through appropriate technologies. Of particular interest to administrators are computer-based communications, management information systems, and desktop application software such as spreadsheets, groupware, and…

  14. Oral administration of SR-110, a peroxynitrite decomposing catalyst, enhances glucose homeostasis, insulin signaling, and islet architecture in B6D2F1 mice fed a high fat diet.

    PubMed

    Johns, Michael; Esmaeili Mohsen Abadi, Sakineh; Malik, Nehal; Lee, Joshua; Neumann, William L; Rausaria, Smita; Imani-Nejad, Maryam; McPherson, Timothy; Schober, Joseph; Kwon, Guim

    2016-04-15

    Peroxynitrite has been implicated in type 2 diabetes and diabetic complications. As a follow-up study to our previous work on SR-135 (Arch Biochem Biophys 577-578: 49-59, 2015), we provide evidence that this series of compounds are effective when administered orally, and their mechanisms of actions extend to the peripheral tissues. A more soluble analogue of SR-135, SR-110 (from a new class of Mn(III) bis(hydroxyphenyl)-dipyrromethene complexes) was orally administered for 2 weeks to B6D2F1 mice fed a high fat-diet (HFD). Mice fed a HFD for 4 months gained significantly higher body weights compared to lean diet-fed mice (52 ± 1.5 g vs 34 ± 1.3 g). SR-110 (10 mg/kg daily) treatment significantly reduced fasting blood glucose and insulin levels, and enhanced glucose tolerance as compared to HFD control or vehicle (peanut butter) group. SR-110 treatment enhanced insulin signaling in the peripheral organs, liver, heart, and skeletal muscle, and reduced lipid accumulation in the liver. Furthermore, SR-110 increased insulin content, restored islet architecture, decreased islet size, and reduced tyrosine nitration. These results suggest that a peroxynitrite decomposing catalyst is effective in improving glucose homeostasis and restoring islet morphology and β-cell insulin content under nutrient overload. PMID:26970045

  15. Administrative Technology and the School Executive: Applying the Systems Approach to Educational Administration.

    ERIC Educational Resources Information Center

    Knezevich, Stephen J., Ed.

    In this era of rapid social change, educational administrators have discovered that new approaches to problem solving and decision making are needed. Systems analysis could afford a promising approach to administrative problems by providing a number of systematic techniques designed to sharpen administrative decision making, enhance efficiency,…

  16. Administration of Bacillus subtilis strains in the rearing water enhances the water quality, growth performance, immune response, and resistance against Vibrio harveyi infection in juvenile white shrimp, Litopenaeus vannamei.

    PubMed

    Zokaeifar, Hadi; Babaei, Nahid; Saad, Che Roos; Kamarudin, Mohd Salleh; Sijam, Kamaruzaman; Balcazar, Jose Luis

    2014-01-01

    In this study, vegetative cell suspensions of two Bacillus subtilis strains, L10 and G1 in equal proportions, was administered at two different doses 10(5) (BM5) and 10(8) (BM8) CFU ml(-1) in the rearing water of shrimp (Litopenaeus vannamei) for eight weeks. Both probiotic groups showed a significant reduction of ammonia, nitrite and nitrate ions under in vitro and in vivo conditions. In comparison to untreated control group, final weight, weight gain, specific growth rate (SGR), food conversion ratio (FCR) and digestive enzymatic activity were significantly greater in the BM5 and BM8 groups. Significant differences for survival were recorded in the BM8 group as compared to the control. Eight weeks after the start of experiment, shrimp were challenged with Vibrio harveyi. Statistical analysis revealed significant differences in shrimp survival between probiotic and control groups. Cumulative mortality of the control group was 80%, whereas cumulative mortality of the shrimp that had been given probiotics was 36.7% with MB8 and 50% with MB5. Subsequently, real-time RT-PCR was employed to determine the mRNA levels of prophenoloxidase (proPO), peroxinectin (PE), lipopolysaccharide- and β-1,3-glucan- binding protein (LGBP) and serine protein (SP). The expression of all immune-related genes studied was only significantly up-regulated in the BM5 group compared to the BM8 and control groups. These results suggest that administration of B. subtilis strains in the rearing water confers beneficial effects for shrimp aquaculture, considering water quality, growth performance, digestive enzymatic activity, immune response and disease resistance. PMID:24161773

  17. AAVshRNA-Mediated Suppression of PTEN in Adult Rats in Combination with Salmon Fibrin Administration Enables Regenerative Growth of Corticospinal Axons and Enhances Recovery of Voluntary Motor Function after Cervical Spinal Cord Injury

    PubMed Central

    2014-01-01

    Conditional genetic deletion of phosphatase and tensin homolog (PTEN) in the sensorimotor cortex of neonatal mice enables regeneration of corticospinal tract (CST) axons after spinal cord injury (SCI). The present study addresses three questions: (1) whether PTEN knockdown in adult rats by nongenetic techniques enables CST regeneration, (2) whether interventions to enable CST regeneration enhance recovery of voluntary motor function, and (3) whether delivery of salmon fibrin into the injury site further enhances CST regeneration and motor recovery. Adult rats were trained in a staircase-reaching task and then received either intracortical injections of AAVshPTEN to delete PTEN or a control vector expressing shRNA for luciferase (AAVshLuc). Rats then received cervical dorsal hemisection injuries and salmon fibrin was injected into the injury site in half the rats, yielding four groups (AAVshPTEN, AAVshLuc, AAVshPTEN + fibrin, and AAVshLuc + fibrin). Forepaw function was assessed for 10 weeks after injury and CST axons were traced by injecting biotin-conjugated dextran amine into the sensorimotor cortex. Rats that received AAVshPTEN alone did not exhibit improved motor function, whereas rats that received AAVshPTEN and salmon fibrin had significantly higher forelimb-reaching scores. Tract tracing revealed that CST axons extended farther caudally in the group that received AAVshPTEN and salmon fibrin versus other groups. There were no significant differences in lesion size between the groups. Together, these data suggest that the combination of PTEN deletion and salmon fibrin injection into the lesion can significantly improve voluntary motor function after SCI by enabling regenerative growth of CST axons. PMID:25057197

  18. Senior Administrators Should Have Administrative Contracts.

    ERIC Educational Resources Information Center

    Posner, Gary J.

    1987-01-01

    Recognizing that termination is viewed by the employee as the equivalent to capital punishment of a career, an administrative contract can reduce the emotional and financial entanglements that often result. Administrative contracts are described. (MLW)

  19. Co-administration strategy to enhance brain accumulation of vandetanib by modulating P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp1/Abcg2) mediated efflux with m-TOR inhibitors.

    PubMed

    Minocha, Mukul; Khurana, Varun; Qin, Bin; Pal, Dhananjay; Mitra, Ashim K

    2012-09-15

    The objectives of this study were (i) to characterize the interaction of vandetanib with P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp1) in vitro and in vivo (ii) to study the modulation of P-gp and BCRP mediated efflux of vandetanib with specific transport inhibitors and m-TOR inhibitors, everolimus and temsirolimus. Cellular accumulation and bi-directional transport studies in MDCKII cell monolayers were conducted to delineate the role of efflux transporters on disposition of vandetanib. Brain distribution studies were conducted in male FVB wild-type mice with vandetanib administered intravenously either alone or in the presence of specific inhibitors and m-TOR inhibitors. In vitro studies suggested that vandetanib is a high affinity substrate of Bcrp1 but is not transported by P-gp. Interestingly, in vivo brain distribution studies in FVB wild type mice indicated that vandetanib penetration into the brain is restricted by both Bcrp1 and P-gp mediated active efflux at the blood brain barrier (BBB). Co-administration of elacridar, a dual P-gp/BCRP inhibitor increased the brain to plasma concentration ratio of vandetanib upto 5 fold. Of the two m-TOR pathway inhibitors examined; everolimus showed potent effect on modulating vandetanib brain penetration whereas no significant affect on vandetanib brain uptake was observed following temsirolimus co-administration. This finding could be clinically relevant as everolimus can provide synergistic pharmacological effect in addition to primary role of vandetanib efflux modulation at BBB for the treatment of brain tumors. PMID:22633931

  20. Novice Administrators: Personality and Administrative Style Changes.

    ERIC Educational Resources Information Center

    Schmidt, Linda J.; Kosmoski, Georgia J.; Pollack, Dennis R.

    Since the advent of effective-schools research findings, educational administration experts have advocated a democratic and collegial leadership style for school administrators. This paper provides the findings of a study that examined 43 beginning administrators (25 females, 32 Caucasians, 9 African-Americans, 2 Hispanics) to determine what…

  1. The oxidation capacity of Mn3O4 nanoparticles is significantly enhanced by anchoring them onto reduced graphene oxide to facilitate regeneration of surface-associated Mn(III).

    PubMed

    Duan, Lin; Wang, Zhongyuan; Hou, Yan; Wang, Zepeng; Gao, Guandao; Chen, Wei; Alvarez, Pedro J J

    2016-10-15

    Metal oxides are often anchored to graphene materials to achieve greater contaminant removal efficiency. To date, the enhanced performance has mainly been attributed to the role of graphene materials as a conductor for electron transfer. Herein, we report a new mechanism via which graphene materials enhance oxidation of organic contaminants by metal oxides. Specifically, Mn3O4-rGO nanocomposites (Mn3O4 nanoparticles anchored to reduced graphene oxide (rGO) nanosheets) enhanced oxidation of 1-naphthylamine (used here as a reaction probe) compared to bare Mn3O4. Spectroscopic analyses (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) show that the rGO component of Mn3O4-rGO was further reduced during the oxidation of 1-naphthylamine, although rGO reduction was not the result of direct interaction with 1-naphthylamine. We postulate that rGO improved the oxidation efficiency of anchored Mn3O4 by re-oxidizing Mn(II) formed from the reaction between Mn3O4 and 1-naphthylamine, thereby regenerating the surface-associated oxidant Mn(III). The proposed role of rGO was verified by separate experiments demonstrating its ability to oxidize dissolved Mn(II) to Mn(III), which subsequently can oxidize 1-naphthylamine. The role of dissolved oxygen in re-oxidizing Mn(II) was ruled out by anoxic (N2-purged) control experiments showing similar results as O2-sparged tests. Opposite pH effects on the oxidation efficiency of Mn3O4-rGO versus bare Mn3O4 were also observed, corroborating the proposed mechanism because higher pH facilitates oxidation of surface-associated Mn(II) even though it lowers the oxidation potential of Mn3O4. Overall, these findings may guide the development of novel metal oxide-graphene nanocomposites for contaminant removal. PMID:27448035

  2. A plan for administrative computing at ANL FY1991 through FY1993

    SciTech Connect

    Caruthers, L.E.; O'Brien, D.E.; Bretscher, M.E.; Hischier, R.C.; Moore, N.J.; Slade, R.G.

    1990-10-01

    In July of 1988, Argonne National Laboratory management approved the restructuring of Computing Services into the Computing and Telecommunications Division, part of the Physical Research area of the Laboratory. One major area of the Computing and Telecommunications Division is Management Information Systems (MIS). A significant aspect of Management Information Systems' work is the development of proposals for new and enhanced administrative computing systems based on an analysis of informational needs. This document represent the outcome of the planning process for FY1991 through FY1993. The introduction of the FY1991 through FY1993 Long-Range Plan assesses the state of administrative computing at ANL and the implications of FY1991 funding recommendations. It includes a history of MIS planning for administrative data processing. This document discusses the strategy and goals which are an important part of administrative data processing plans for the Laboratory. It also describes the management guidelines established by the Administrative Data Processing Oversight Committee for the proposal and implementation of administrative computing systems. Summaries of the proposals for new or enhanced administrative computing systems presented by individual divisions or departments with assistance of Management Information Systems, to the Administrative Data Processing Oversight Committee are given. The detailed tables in this paper give information on how much the resources to develop and implement a given systems will cost its users. The tables include development costs, computing/operations costs, software and hardware costs, and efforts costs. They include both systems funded by Laboratory General Expense and systems funded by the users themselves.

  3. Short-term administration of basic fibroblast growth factor enhances coronary collateral development without exacerbating atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic rabbits with acute myocardial infarction.

    PubMed

    Zhang, Chunxiang; Yang, Jian; Feng, Jianzhang; Jennings, Lisa K

    2002-08-01

    We evaluated the effect of basic fibroblast growth factor (bFGF) on the extent of atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic animals with acute myocardial infarction (AMI). Fifty-six rabbits were fed a 1% cholesterol diet. Balloon injury of iliac arteries and experimental acute myocardial infarction were induced in the same animals. Rabbits were then randomized to a bFGF group (20 pg/day, intravenously) or a control group (intravenous saline solution). The beneficial effects of bFGF on cardiac function, infarct size, and collateral vessel development, and the possible effect on vasoproliferation of balloon-injured vessels, were measured after 1 and 2 weeks. The extent of atherosclerosis was measured after 1, 2, and 4 weeks. Our results showed that bFGF significantly reduced infarct size and increased collateral-vessel density (P <.01) in infarct areas. Cardiac function was better in the bFGF group than in corresponding controls (P <.05). Similar beneficial effects of bFGF were noted in animals after 1- and 2-week treatments. However, the extent of atherosclerosis and the vasoproliferation in chronic atherosclerotic vessels induced by balloon injury and cholesterol diet were not significantly different between the two groups. Our results suggest that short-term treatment with bFGF enhances collateral development and produces maximum therapeutic benefits without exacerbating atherosclerosis and cell proliferation in stenotic vessels after AMI in atherosclerotic rabbits. PMID:12228768

  4. Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection.

    PubMed

    Chitradevi, Sekar Tamil Selvi; Kaur, Gurpreet; Uppalapati, Sivaramakrishna; Yadav, Anandprakash; Singh, Dependrapratap; Bansal, Anju

    2015-11-01

    Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-γ) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%-70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%-85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants. PMID:25640657

  5. Organization/Administration.

    ERIC Educational Resources Information Center

    Chaffee, Ellen Earle

    Patterns that emerged from reviewing 26 syllabi for courses on organization and administration in higher education are discussed, and six sample syllabi are presented. The syllabi focused more on organization than administration. Of the 26 syllabi, 19 dealt with organization and administration generally; 5 with administration in a specific…

  6. Role of neutrophils in hepatotoxicity induced by oral acetaminophen administration in rats.

    PubMed

    Smith, G S; Nadig, D E; Kokoska, E R; Solomon, H; Tiniakos, D G; Miller, T A

    1998-12-01

    Acetaminophen (APAP) is a common analgesic and antipyretic compound which, when administered in high doses, has been associated with significant morbidity and mortality, secondary to hepatic toxicity. To date, the mechanism(s) whereby APAP induces liver injury remains to be delineated. This study investigated the potential role of neutrophils as contributors to liver injury in rats administered sublethal doses of APAP. Oral APAP administration (650 mg/kg) was associated with increases in serum alanine transaminase (ALT) levels indicating biochemical evidence of significant liver damage. Furthermore, histological analyses verified significant hepatocellular necrosis as well as enhanced myeloperoxidase staining in these liver specimens. However, if animals were pretreated with antineutrophil sera prior to APAP administration, neutrophil counts remained depressed, ALT levels were significantly decreased, and the degree of liver injury was attenuated on a histological level. Taken together these data suggest that neutrophils mediate, at least in part, the hepatotoxic effects of oral acetaminophen administration in rats. PMID:9878321

  7. Enhanced therapeutic anti-inflammatory effect of betamethasone on topical administration with low-frequency, low-intensity (20 kHz, 100 mW/cm(2)) ultrasound exposure on carrageenan-induced arthritis in a mouse model.

    PubMed

    Cohen, Gadi; Natsheh, Hiba; Sunny, Youhan; Bawiec, Christopher R; Touitou, Elka; Lerman, Melissa A; Lazarovici, Philip; Lewin, Peter A

    2015-09-01

    The purpose of this work was to investigate whether low-frequency, low-intensity (20 kHz, <100 mW/cm(2), spatial-peak, temporal-peak intensity) ultrasound, delivered with a lightweight (<100 g), tether-free, fully wearable, battery-powered applicator, is capable of reducing inflammation in a mouse model of rheumatoid arthritis. The therapeutic, acute, anti-inflammatory effect was estimated from the relative swelling induced in mice hindlimb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near-infrared labeled 2-deoxyglucose. The outcome of the experiments indicated that the combination of ultrasound exposure and topical application of 0.1% (w/w) betamethasone gel resulted in statistically significantly (p < 0.05) enhanced anti-inflammatory activity in comparison with drug or ultrasound treatment alone. The present study underscores the potential benefits of low-frequency, low-intensity ultrasound-assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, tolerable low-frequency, low-intensity ultrasound-promoted non-invasive drug delivery. PMID:26003010

  8. Significant enhancement of 11-Hydroxy-THC detection by formation of picolinic acid esters and application of liquid chromatography/multi stage mass spectrometry (LC-MS(3) ): Application to hair and oral fluid analysis.

    PubMed

    Thieme, Detlef; Sachs, Ulf; Sachs, Hans; Moore, Christine

    2015-07-01

    Formation of picolinic acid esters of hydroxylated drugs or their biotransformation products is a promising tool to improve their mass spectrometric ionization efficiency, alter their fragmentation behaviour and enhance sensitivity and specificity of their detection. The procedure was optimized and tested for the detection of cannabinoids, which proved to be most challenging when dealing with alternative specimens, for example hair and oral fluid. In particular, the detection of the THC metabolites hydroxyl-THC and carboxy-THC requires ultimate sensitivity because of their poor incorporation into hair or saliva. Both biotransformation products are widely accepted as incorporation markers to distinguish drug consumption from passive contamination. The derivatization procedure was carried out by adding a mixture of picolinic acid, 4-(dimethylamino)pyridine and 2-methyl-6-nitrobenzoic anhydride in tetrahydrofuran/triethylamine to the dry extraction residues. Resulting derivatives were found to be very stable and could be reconstituted in aqueous or organic buffers and subsequently analyzed by liquid chromatography-mass spectrometry (LC-MS). Owing to the complex consecutive fragmentation patterns, the application of multistage MS3 proved to be extremely useful for a sensitive identification of doubly picolinated hydroxy-THC in complex matrices. The detection limits - estimated by comparison of corresponding signal-to-noise ratios - increased by a factor of 100 following picolination. All other species examined, like cannabinol, THC, cannabidiol, and carboxy-THC, could also be derivatized exhibiting only moderate sensitivity improvements. The assay was systematically tested using hair samples and exemplarily applied to oral fluid. Concentrations of OH-THC identified in THC-positive hair samples ranged from 0.02 to 0.29pg/mg. PMID:25345394

  9. Significant lexical relationships

    SciTech Connect

    Pedersen, T.; Kayaalp, M.; Bruce, R.

    1996-12-31

    Statistical NLP inevitably deals with a large number of rare events. As a consequence, NLP data often violates the assumptions implicit in traditional statistical procedures such as significance testing. We describe a significance test, an exact conditional test, that is appropriate for NLP data and can be performed using freely available software. We apply this test to the study of lexical relationships and demonstrate that the results obtained using this test are both theoretically more reliable and different from the results obtained using previously applied tests.

  10. Neurotensin enhances estradiol induced DNA synthesis in immature rat uterus

    SciTech Connect

    Mistry, A.; Vijayan, E.

    1985-05-27

    Systemic administration of Neurotensin, a tridecapeptide, in immature rats treated with estradiol benzoate significantly enhances uterine DNA synthesis as reflected by the incorporation of /sup 3/H-thymidine. The peptide may have a direct action on the uterus. Substance P, a related peptide, had no effect on uterine DNA synthesis. 18 references, 4 tables.

  11. Monitoring Items in Real Time to Enhance CAT Security

    ERIC Educational Resources Information Center

    Zhang, Jinming; Li, Jie

    2016-01-01

    An IRT-based sequential procedure is developed to monitor items for enhancing test security. The procedure uses a series of statistical hypothesis tests to examine whether the statistical characteristics of each item under inspection have changed significantly during CAT administration. This procedure is compared with a previously developed…

  12. Statistical Significance Testing.

    ERIC Educational Resources Information Center

    McLean, James E., Ed.; Kaufman, Alan S., Ed.

    1998-01-01

    The controversy about the use or misuse of statistical significance testing has become the major methodological issue in educational research. This special issue contains three articles that explore the controversy, three commentaries on these articles, an overall response, and three rejoinders by the first three authors. They are: (1)…

  13. Lack of Statistical Significance

    ERIC Educational Resources Information Center

    Kehle, Thomas J.; Bray, Melissa A.; Chafouleas, Sandra M.; Kawano, Takuji

    2007-01-01

    Criticism has been leveled against the use of statistical significance testing (SST) in many disciplines. However, the field of school psychology has been largely devoid of critiques of SST. Inspection of the primary journals in school psychology indicated numerous examples of SST with nonrandom samples and/or samples of convenience. In this…

  14. Administrative Team Contracts. The Administrative Team Career Development Series, Book 5.

    ERIC Educational Resources Information Center

    American Association of School Administrators, Arlington, VA.

    Observing that effective employment contracts communicate the school board's expectations to individual administrators and enhance working relationships, this guide informs boards developing contracts for members of management teams of available alternatives. The importance of clarifying the relationship between the administrator and the board,…

  15. Administration for Community Living

    MedlinePlus

    ... by Acting Assistant Secretary for Aging and ACL Administrator Edwin Walker at the HCBS Conference (08/29/ ... Remarks by Assistant Secretary on Aging and ACL Administrator Kathy Greenlee at the n4a Answers on Aging ...

  16. The New Administrative Computing.

    ERIC Educational Resources Information Center

    Green, Kenneth C.

    1988-01-01

    The past decade has seen dramatic changes in administrative computing, including more systems, more applications, a new group of computer users, and new opportunities for computer use in campus administration. (Author/MSE)

  17. Transportation Security Administration

    MedlinePlus

    ... content Official website of the Department of Homeland Security Transportation Security Administration When I fly can I bring my... ... to know if you could bring through the security checkpoint. Main menu Administrator Travel Security Screening Special ...

  18. One-year outcomes of out-of-hospital administration of intravenous glucose, insulin, and potassium (GIK) in patients with suspected acute coronary syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial).

    PubMed

    Selker, Harry P; Udelson, James E; Massaro, Joseph M; Ruthazer, Robin; D'Agostino, Ralph B; Griffith, John L; Sheehan, Patricia R; Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin; Vickery, Ellen M; Atkins, James M; Aufderheide, Tom P; Sayah, Assaad J; Pirrallo, Ronald G; Levy, Michael K; Richards, Michael E; Braude, Darren A; Doyle, Delanor D; Frascone, Ralph J; Kosiak, Donald J; Leaming, James M; Van Gelder, Carin M; Walter, Gert-Paul; Wayne, Marvin A; Woolard, Robert H; Beshansky, Joni R

    2014-05-15

    The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (HR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced. PMID:24792735

  19. NASA, NOAA administrators nominated

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    President Ronald Reagan recently said he intended to nominate James Montgomery Beggs as NASA Administrator and John V. Byrne as NOAA Administrator. These two positions are key scientific posts that have been vacant since the start of the Reagan administration on January 20. The President also said he intends to nominate Hans Mark as NASA Deputy Administrator. At press time, Reagan had not designated his nominee for the director of the Office of Science and Technology Policy.

  20. Significant Tsunami Events

    NASA Astrophysics Data System (ADS)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  1. A Philosophy of Administration.

    ERIC Educational Resources Information Center

    Bruening, William H.

    Justification is given for paying relatively large salaries to college administrators, specifically the president or chancellor and the chief academic officer. Three administrative task areas are discussed as criteria: management, administration per se, and leadership. It is contended that only leadership can be used as a criterion for…

  2. School Business Administration.

    ERIC Educational Resources Information Center

    Jordan, K. Forbis; And Others

    This textbook reviews the principal concerns within each of 13 major responsibility areas in school business administration. The first chapter assesses the political, social, and economic context in which schools function and school administrators work. The role and function of the school business administrator within this context is addressed in…

  3. Oral administration of inosine produces antidepressant-like effects in mice

    PubMed Central

    Muto, Junko; Lee, Hosung; Lee, Hyunjin; Uwaya, Akemi; Park, Jonghyuk; Nakajima, Sanae; Nagata, Kazufumi; Ohno, Makoto; Ohsawa, Ikuroh; Mikami, Toshio

    2014-01-01

    Inosine, a breakdown product of adenosine, has recently been shown to exert immunomodulatory and neuroprotective effects. We show here that the oral administration of inosine has antidepressant-like effects in two animal models. Inosine significantly enhanced neurite outgrowth and viability of primary cultured neocortical neurons, which was suppressed by adenosine A1 and A2A receptor agonists. Oral administration of inosine to mice transiently increased its concentration in the brain and enhanced neuronal proliferation in the dentate gyrus, accompanied by phosphorylation of mitogen-activated protein kinase and increase in transcript level of brain-derived neurotrophic factor. In stress models, oral inosine prevented an increase in immobility time in forced swim test after chronically unexpected stress and mitigated a reduction in sucrose preference after chronic social defeat stress. These results indicate that oral administration of inosine has the potential to prevent depressive disorder via adenosine receptors. PMID:24569499

  4. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

    PubMed

    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes. PMID:25757438

  5. 45 CFR 1351.1 - Significant terms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, FAMILY AND YOUTH SERVICES BUREAU RUNAWAY AND HOMELESS YOUTH PROGRAM Definition of Terms § 1351.1 Significant terms. For the... homeless youth and their families, following the youth's return home or placement in alternative...

  6. 45 CFR 1351.1 - Significant terms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, FAMILY AND YOUTH SERVICES BUREAU RUNAWAY AND HOMELESS YOUTH PROGRAM Definition of Terms § 1351.1 Significant terms. For the... homeless youth and their families, following the youth's return home or placement in alternative...

  7. 45 CFR 1351.1 - Significant terms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, FAMILY AND YOUTH SERVICES BUREAU RUNAWAY AND HOMELESS YOUTH PROGRAM Definition of Terms § 1351.1 Significant terms. For the... homeless youth and their families, following the youth's return home or placement in alternative...

  8. 45 CFR 1351.1 - Significant terms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Significant terms. 1351.1 Section 1351.1 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, FAMILY AND YOUTH SERVICES BUREAU RUNAWAY AND HOMELESS...

  9. Co-Administration of Molecular Adjuvants Expressing NF-Kappa B Subunit p65/RelA or Type-1 Transactivator T-bet Enhance Antigen Specific DNA Vaccine-Induced Immunity

    PubMed Central

    Shedlock, Devon J.; Tingey, Colleen; Mahadevan, Lavanya; Hutnick, Natalie; Reuschel, Emma L.; Kudchodkar, Sagar; Flingai, Seleeke; Yan, Jenny; Kim, Joseph J.; Ugen, Kenneth E.; Weiner, David B.; Muthumani, Kar

    2014-01-01

    DNA vaccine-induced immunity can be enhanced by the co-delivery of synthetic gene-encoding molecular adjuvants. Many of these adjuvants have included cytokines, chemokines or co-stimulatory molecules that have been demonstrated to enhance vaccine-induced immunity by increasing the magnitude or type of immune responses and/or protective efficacy. In this way, through the use of adjuvants, immune responses can be highly customizable and functionally tailored for optimal efficacy against pathogen specific (i.e., infectious agent) or non-pathogen (i.e., cancer) antigens. In the novel study presented here, we examined the use of cellular transcription factors as molecular adjuvants. Specifically the co-delivery of (a) RelA, a subunit of the NF-κB transcription complex or (b) T-bet, a Th1-specific T box transcription factor, along with a prototypical DNA vaccine expressing HIV-1 proteins was evaluated. As well, all of the vaccines and adjuvants were administered to mice using in vivo electroporation (EP), a technology demonstrated to dramatically increase plasmid DNA transfection and subsequent transgene expression with concomitant enhancement of vaccine induced immune responses. As such, this study demonstrated that co-delivery of either adjuvant resulted in enhanced T and B cell responses, specifically characterized by increased T cell numbers, IFN-γ production, as well as enhanced antibody responses. This study demonstrates the use of cellular transcription factors as adjuvants for enhancing DNA vaccine-induced immunity. PMID:26344618

  10. Co-Administration of Molecular Adjuvants Expressing NF-Kappa B Subunit p65/RelA or Type-1 Transactivator T-bet Enhance Antigen Specific DNA Vaccine-Induced Immunity.

    PubMed

    Shedlock, Devon J; Tingey, Colleen; Mahadevan, Lavanya; Hutnick, Natalie; Reuschel, Emma L; Kudchodkar, Sagar; Flingai, Seleeke; Yan, Jenny; Kim, Joseph J; Ugen, Kenneth E; Weiner, David B; Muthumani, Kar

    2014-01-01

    DNA vaccine-induced immunity can be enhanced by the co-delivery of synthetic gene-encoding molecular adjuvants. Many of these adjuvants have included cytokines, chemokines or co-stimulatory molecules that have been demonstrated to enhance vaccine-induced immunity by increasing the magnitude or type of immune responses and/or protective efficacy. In this way, through the use of adjuvants, immune responses can be highly customizable and functionally tailored for optimal efficacy against pathogen specific (i.e., infectious agent) or non-pathogen (i.e., cancer) antigens. In the novel study presented here, we examined the use of cellular transcription factors as molecular adjuvants. Specifically the co-delivery of (a) RelA, a subunit of the NF-κB transcription complex or (b) T-bet, a Th1-specific T box transcription factor, along with a prototypical DNA vaccine expressing HIV-1 proteins was evaluated. As well, all of the vaccines and adjuvants were administered to mice using in vivo electroporation (EP), a technology demonstrated to dramatically increase plasmid DNA transfection and subsequent transgene expression with concomitant enhancement of vaccine induced immune responses. As such, this study demonstrated that co-delivery of either adjuvant resulted in enhanced T and B cell responses, specifically characterized by increased T cell numbers, IFN-γ production, as well as enhanced antibody responses. This study demonstrates the use of cellular transcription factors as adjuvants for enhancing DNA vaccine-induced immunity. PMID:26344618

  11. Statistical or biological significance?

    PubMed

    Saxon, Emma

    2015-01-01

    Oat plants grown at an agricultural research facility produce higher yields in Field 1 than in Field 2, under well fertilised conditions and with similar weather exposure; all oat plants in both fields are healthy and show no sign of disease. In this study, the authors hypothesised that the soil microbial community might be different in each field, and these differences might explain the difference in oat plant growth. They carried out a metagenomic analysis of the 16 s ribosomal 'signature' sequences from bacteria in 50 randomly located soil samples in each field to determine the composition of the bacterial community. The study identified >1000 species, most of which were present in both fields. The authors identified two plant growth-promoting species that were significantly reduced in soil from Field 2 (Student's t-test P < 0.05), and concluded that these species might have contributed to reduced yield. PMID:26541972

  12. Anthropological significance of phenylketonuria.

    PubMed

    Saugstad, L F

    1975-01-01

    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations. PMID:803884

  13. Computerized medication administration records decrease medication occurrences.

    PubMed

    Wilson, A L; Hill, J J; Wilson, R G; Nipper, K; Kwon, I W

    1997-04-01

    Studies have demonstrated that medication errors occur at a number of locations in the continuum between ordering of drug therapy and administration of the medication. Computer management of patient medication profiles offers the opportunity to enhance communication between pharmacists and nurses, and to decrease medication errors and delays in delivery of therapy. A number of authors have postulated that computerization of medication profiles would enhance medication delivery accuracy and timeliness, but no study has demonstrated this improvement. We report the results of a retrospective analysis undertaken to assess the improvements resulting from sharing a computerized medication record. We used a broader definition of medication occurrences that includes the more traditional definition, and averted errors, delays in delivery of medications and information, and disagreements between pharmacy and nursing medication profiles. We compared medication occurrences reported through an existing internal system between two periods; the first when separate pharmacy and nursing medication records were used, and the second period when a shared medication record was used by pharmacy and nursing. Average medication occurrences per admission decreased from 0.1084 to 0.0658 (p < 0.01). Medication occurrences per dose decreased from 0.0005 to 0.0003 (p < 0.01). The use of a shared medication record by pharmacy and nursing led to a statistically significant decrease in medication occurrences. Information shared between the two professions allowed timely resolution of discrepancies in medication orders, leading to better execution of drug therapy, decreased medication occurrences, and increased efficiency. PMID:10166241

  14. Transdermal absorption of memantin--effect of chemical enhancers, iontophoresis, and role of enhancer lipophilicity.

    PubMed

    del Rio-Sancho, S; Serna-Jiménez, C E; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; Merino, V; López-Castellano, A

    2012-09-01

    The transdermal administration of memantine may have advantages with respect to oral therapy when treating advanced stages of Alzheimer's disease. With the ultimate objective of administrating memantine through a transdermal patch, the absorption of the drug across skin was evaluated by means of in vitro permeation studies. The effect of several chemical enhancers was studied in order to enhance percutaneous absorption of the memantine. The iontophoretic transdermal transport of memantine hydrochloride using a current density of 0.5 mA/cm(2) was also investigated. Results demonstrated that pre-treatment of the skin with R-(+)-limonene, laurocapram, decenoic acid, or oleic acid produced a statistically significant increment in the transdermal flux of memantine hydrochloride with respect to the control. Iontophoresis exhibited the greatest ability to enhance the flux of drug with respect to the control; nevertheless, the results obtained with R-(+)-limonene indicate that this compound could be of great use as a percutaneous enhancer in a memantine transdermal delivery system. In this study, the relationship between enhancement activity and lipophilicity was also studied. Satisfactory correlations have been obtained between the optimum lipophilicity of the enhancer and n-octanol/water partition coefficients of drugs. This relationship is a very useful tool that could allow to reduce time and to optimize the selection of appropriate enhancers for transdermal formulations. PMID:22732268

  15. The effects of amphetamine, butorphanol, and their combination on cocaine self-administration.

    PubMed

    Smith, Mark A; Pennock, Michael M; Pitts, Elizabeth G; Walker, Katherine L; Lang, Kimberly C

    2014-11-01

    There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies. Once self-administration was acquired, rats were divided into four different groups and treated chronically for 20 days with (1) saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and butorphanol. During chronic treatment, cocaine self-administration was examined on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. On the FR schedule, butorphanol significantly decreased cocaine self-administration, but this effect was not enhanced by amphetamine. On the PR schedule, amphetamine and butorphanol non-significantly decreased cocaine self-administration when administered alone but significantly decreased cocaine self-administration when administered in combination. These data suggest that under some conditions (e.g., when the response requirement of cocaine is high), a dual stimulant-opioid pharmacotherapy may be more effective than a single-drug monotherapy. PMID:25127681

  16. The Effects of Amphetamine, Butorphanol, and Their Combination on Cocaine Self-Administration

    PubMed Central

    Smith, Mark A.; Pennock, Michael M.; Pitts, Elizabeth G.; Walker, Katherine L.; Lang, Kimberly C.

    2014-01-01

    There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies. Once self-administration was acquired, rats were divided into four different groups and treated chronically for 20 days with (1) saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and butorphanol. During chronic treatment, cocaine self-administration was examined on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. On the FR schedule, butorphanol significantly decreased cocaine self-administration, but this effect was not enhanced by amphetamine. On the PR schedule, amphetamine and butorphanol non-significantly decreased cocaine self-administration when administered alone but significantly decreased cocaine self-administration when administered in combination. These data suggest that under some conditions (e.g., when the response requirement of cocaine is high), a dual stimulant-opioid pharmacotherapy may be more effective than a single-drug monotherapy. PMID:25127681

  17. Significant Radionuclides Determination

    SciTech Connect

    Jo A. Ziegler

    2001-07-31

    The purpose of this calculation is to identify radionuclides that are significant to offsite doses from potential preclosure events for spent nuclear fuel (SNF) and high-level radioactive waste expected to be received at the potential Monitored Geologic Repository (MGR). In this calculation, high-level radioactive waste is included in references to DOE SNF. A previous document, ''DOE SNF DBE Offsite Dose Calculations'' (CRWMS M&O 1999b), calculated the source terms and offsite doses for Department of Energy (DOE) and Naval SNF for use in design basis event analyses. This calculation reproduces only DOE SNF work (i.e., no naval SNF work is included in this calculation) created in ''DOE SNF DBE Offsite Dose Calculations'' and expands the calculation to include DOE SNF expected to produce a high dose consequence (even though the quantity of the SNF is expected to be small) and SNF owned by commercial nuclear power producers. The calculation does not address any specific off-normal/DBE event scenarios for receiving, handling, or packaging of SNF. The results of this calculation are developed for comparative analysis to establish the important radionuclides and do not represent the final source terms to be used for license application. This calculation will be used as input to preclosure safety analyses and is performed in accordance with procedure AP-3.12Q, ''Calculations'', and is subject to the requirements of DOE/RW-0333P, ''Quality Assurance Requirements and Description'' (DOE 2000) as determined by the activity evaluation contained in ''Technical Work Plan for: Preclosure Safety Analysis, TWP-MGR-SE-000010'' (CRWMS M&O 2000b) in accordance with procedure AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities''.

  18. Fungi producing significant mycotoxins.

    PubMed

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

  19. Bear Valley Creek, Idaho Mining Enhancement: Fifteen Years Later

    NASA Astrophysics Data System (ADS)

    Ray, H. L.; Bacon, K. L.; Wadsworth, P. R.

    2005-05-01

    In 1988-89 an enhancement effort was initiated by the Shoshone-Bannock Tribes and Bonneville Power Administration in a mined section of Bear Valley Creek, Idaho. Monitoring and evaluation conducted between 1984 and 2004 above, within, and below the enhancement area included; changes in densities of non-anadromous salmonids, natural production of Chinook salmon Oncorhynchus tshawytscha, recovery of the macroinvertebrates, changes in surface and benthic sediment, and visual vegetation progression. Mean densities of non-anadromous salmonids in pools showed a significant increase from pre to post enhancement within and below the enhancement area. Chinook salmon parr numbers were significantly related to the number of redds the previous year. Preliminary results indicate that the macroinvertebrate community within the enhancement area may be recovering. Percent surface fine sediment decreased significantly from pre to post enhancement within and below the enhancement area. Trends in cumulative percent benthic fine sediment were similar above within and below the enhancement area indicating no new additional incorporation of fine sediment to the benthos. Photo point monitoring in 1989 and 2004 shows progression of vegetation development within the enhancement area with good cover achieved. Long term monitoring of Bear Valley Creek indicates recovery from the mining impact and successful enhancement effort.

  20. Attenuation of methylphenidate-induced sensitization by co-administration of buspirone.

    PubMed

    Alam, Nausheen; Najam, Rahila; Naeem, Sadaf

    2016-03-01

    Methylphenidate, which inhibit dopamine transporter is effective in the treatment of ADHD (attention deficit hyperactivity disorder), but long term use of this drug is often associated with addiction and dependence. Locomotor sensitization development to psychostimulants like methylphenidate is an important contributor to drug abuse induced by psychostimulants. Different studies have shown that long term administration of drugs of abuse increases the effectiveness of 5-hydroxytryptamine (5-HT)-1A somatodendritic receptors. Repeated buspirone administration reduces the effectiveness of 5-HT1A somatodendritic receptors. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced sensitization. The motor activity was compared by using familiar and novel environments after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0 mg/kg/day enhanced motor activity in home cage i.e. activity of familiar environment monitored at alternate day. Locomotor enhancing effects of methylphenidate were augmented on 13th day of drug administration suggesting sensitization induced by the drug. The sensitization effects were significant in home cage monitored on alternate day and also in an open field monitored weekly. Buspirone co-administration at a dose of 10 mg/kg/day prevented methylphenidate-induced sensitization. It is suggested that the sensitization development to methylphenidate may oppose by buspirone co-administration due to the reduction in the sensitivity of 5-HT1A somatodendritic receptors. These findings may help extend future therapeutics in ADHD. PMID:27087081

  1. Significantly enhanced dehydrogenation properties of calcium borohydride combined with urea.

    PubMed

    Chu, Hailiang; Qiu, Shujun; Liu, Lin; Zou, Yongjin; Xiang, Cuili; Zhang, Huanzhi; Xu, Fen; Sun, Lixian; Zhou, Huaiying; Wu, Guotao

    2014-11-01

    The interaction of [BH(x)]- and [NH(x)]-containing species gives rise to molecular hydrogen and the establishment of the B-N bond. Up to now, metal amides and ammonia are the commonly used [NH(x)] sources. Herein, urea, an organic carbonyl diamide, was used to react with Ca(BH4)2. A new type of complex hydride Ca(BH4)2·4CO(NH2)2 was synthesized with release of ca. 5.2 wt% hydrogen below 250 °C. PMID:25186984

  2. Intragastric administration of glutamate increases REM sleep in rats.

    PubMed

    Datta, Karuna; Kumar, Deependra; Mallick, Hruda Nanda

    2013-10-01

    Monosodium glutamate, a umami taste substance is commonly used flavor enhancer. The effect of intragastric administration of 1.5 ml of 0.12M monosodium glutamate on sleep-wake was studied in 10 adult male Wistar rats. Sleep-wake parameters were recorded through chronically implanted electroencephalogram, electrooculogram and electromyogram electrodes using a digital recording system (BIOPAC system Inc. BSL PRO 36, USA). The sleep-wake was recorded for 6h after the intragastric administration of either glutamate or saline. Sleep-wake stages were analyzed as wake, slow wave sleep and REM sleep. Compared to saline, intragastric administration of glutamate significantly increased REM sleep duration and episode frequency. REM sleep duration was increased in all the three 2h bins, 10:00-12:00 h (p=0.037), 12:00-14:00 h (p=0.037) and 14:00-16:00 h (p=0.007). The slow wave sleep and total sleep time were not affected. It is concluded that intragastric glutamate administration increases REM sleep. PMID:24055576

  3. Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

    PubMed Central

    Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

    2016-01-01

    The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain. PMID:27345430

  4. Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor.

    PubMed

    Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E

    2016-01-01

    The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain. PMID:27345430

  5. Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

    NASA Astrophysics Data System (ADS)

    Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

    2016-06-01

    The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

  6. Veterans Administration Databases

    Cancer.gov

    The Veterans Administration Information Resource Center provides database and informatics experts, customer service, expert advice, information products, and web technology to VA researchers and others.

  7. Significance of biofilms in dentistry.

    PubMed

    Wróblewska, Marta; Strużycka, Izabela; Mierzwińska-Nastalska, Elżbieta

    2015-01-01

    In the past decades significant scientific progress has taken place in the knowledge about biofilms. They constitute multilayer conglomerates of bacteria and fungi, surrounded by carbohydrates which they produce, as well as substances derived from saliva and gingival fluid. Modern techniques showed significant diversity of the biofilm environment and a system of microbial communication (quorum sensing), enhancing their survival. At present it is believed that the majority of infections, particularly chronic with exacerbations, are a result of biofilm formation, particularly in the presence of biomaterials. It should be emphasised that penetration of antibiotics and other antimicrobial agents into deeper layers of a biofilm is poor, causing therapeutic problems and necessitating sometimes removal of the implant or prosthesis. Biofilms play an increasing role in dentistry as a result of more and more broad use in dental practice of plastic and implantable materials. Biofilms are produced on the surfaces of teeth as dental plaque, in the para-nasal sinuses, on prostheses, dental implants, as well as in waterlines of a dental unit, constituting a particular risk for severely immunocompromised patients. New methods of therapy and prevention of infections linked to biofilms are under development. PMID:27139354

  8. Preparing College Administrators: Fact and Fancy.

    ERIC Educational Resources Information Center

    Stalcup, Robert J.; Wilson, Jerry L.

    The universality of administrative functions and tasks is sufficiently established to make special preparation programs for any one group of higher education administrators unjustifiable. This thesis is based on research undertaken to determine if significant differences existed in the functions or tasks performed by presidents, vice-presidents of…

  9. Enhanced Absorption Study of Ginsenoside Compound K (20-O-β-(D-Glucopyranosyl)-20(S)-protopanaxadiol) after Oral Administration of Fermented Red Ginseng Extract (HYFRG™) in Healthy Korean Volunteers and Rats

    PubMed Central

    Choi, Il-Dong; Ryu, Ju-Hee; Lee, Dong-Eun; Lee, Myoung-Hee; Shim, Jae-Joong; Ahn, Young-Tae; Sim, Jae-Hun; Huh, Chul-Sung; Shim, Wang-Seob; Yim, Sung-Vin; Chung, Eun-Kyoung

    2016-01-01

    To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open-label, randomized, single-dose, fasting, and one-period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD) of AUC0–t and Cmax of compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2- and 80-fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL), respectively; in case of Sprague Dawley rats the mean (±SD) of AUC0–t and Cmax of compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3- and 6.0-fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL), respectively. Tmax of compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG. PMID:27516803

  10. Decreased synthesis of DNA in regenerating rat liver after the administration of reserpine

    PubMed Central

    Ćihák, A.; Vaptzarova, K.

    1973-01-01

    1. Reserpine given to rats before the enhanced synthesis of DNA begins 14h after partial hepatectomy markedly depresses thymidine uptake into DNA at 24 hours. 2. At this time decreased activity of liver thymidine kinase but unchanged thymidine 5′-nucleotidase were observed. 3. Reserpine has no effect on DNA synthesis when administered simultaneously with the labelled thymidine 2 h before killing. 4. With depressed DNA synthesis after reserpine administration there is no significant decrease of liver RNA synthesis. PMID:4793440

  11. CDS - Database Administrator's Guide

    NASA Astrophysics Data System (ADS)

    Day, J. P.

    This guide aims to instruct the CDS database administrator in: o The CDS file system. o The CDS index files. o The procedure for assimilating a new CDS tape into the database. It is assumed that the administrator has read SUN/79.

  12. Vocational Education Administration Handbook.

    ERIC Educational Resources Information Center

    Ryals, Karen, Ed.; Doherty, Susan Sloan, Ed.

    This handbook for vocational administrators presents an overview of vocational education programs, services, and administrative structures in Alaska. The manual contains three parts. The first, brief section introduces secondary vocational education and lists its enabling legislation. The second part presents a detailed overview of vocational…

  13. Reframing Research Administration

    ERIC Educational Resources Information Center

    Cole, Sharon Stewart

    2010-01-01

    The purpose of this paper is to inform administrators and organizational leaders that a change in the support offered to faculty and the environment of research administration is desirable. This recommendation is supported by the results of a Delphi study that was undertaken to gather expert opinions and recommendations from research faculty…

  14. Justifying Educational Administration.

    ERIC Educational Resources Information Center

    Evers, Colin; Lakomski, Gabriele

    1993-01-01

    The traditional conceptions of science dominating educational administration are mistaken. Unacceptable epistemologies, like those implicit in logical positivism, justify knowledge solely in terms of empirical adequacy. An improved science of educational administration embraces a coherent global theory accounting for all the phenomena of human…

  15. Migrant Education Administrative Guide.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh. Div. of Compensatory Education.

    Relating specifically to the North Carolina migrant education program's administrative responsibilities, this guide is designed to aid administrators in program management, monitoring project activities, project evaluation, self-assessment, determining needs for training and staff development, site-visit preparation, policy development, and…

  16. DIMENSIONS OF ADMINISTRATIVE PERFORMANCE.

    ERIC Educational Resources Information Center

    HEMPHILL, JOHN; AND OTHERS

    THE MAJOR OBJECTIVES WERE TO DEVELOP CRITERIA FOR THE EVALUATION OF SCHOOL ADMINISTRATION, TO DEFINE THE NATURE OF THE JOB, AND TO DEVELOP AN INSTRUMENT FOR THE SELECTION OF ADMINISTRATORS. THE ELEMENTARY SCHOOL PRINCIPAL WAS CHOSEN FOR THE STUDY BECAUSE OF THE HOST OF PROBLEMS RELATED TO THE CONDUCT OF AN EDUCATIONAL PROGRAM, INCLUDING THE…

  17. Test Administration Models

    ERIC Educational Resources Information Center

    Becker, Kirk A.; Bergstrom, Betty A.

    2013-01-01

    The need for increased exam security, improved test formats, more flexible scheduling, better measurement, and more efficient administrative processes has caused testing agencies to consider converting the administration of their exams from paper-and-pencil to computer-based testing (CBT). Many decisions must be made in order to provide an optimal…

  18. Networked Administration Streamlines Operations.

    ERIC Educational Resources Information Center

    School Planning and Management, 1996

    1996-01-01

    An Iowa school district has retooled its computer systems for more standardized administration. In addition to administration, the district is doing inhouse databasing of financial accounting, and doing inhouse scheduling and grade reporting. A partnership with the Chamber of Commerce contributed $500,000 for the network system. (MLF)

  19. The Administrative Power Grab

    ERIC Educational Resources Information Center

    Sorenson, Richard D.

    2007-01-01

    Administrative power for some school teachers can be an aphrodisiac that can be applied negatively, especially when a leader has devastating instinct for the weaknesses of others. A leader's intellect and heart closes shop and ceases to function when drunk on power. In this article, the author describes how the use of administrative power can be…

  20. Champions of Children. Administrators . . .

    ERIC Educational Resources Information Center

    Chaffee, John; Olds, H. Robert

    Today, in an era of taxpayer revolts, lack of clarity in values, and changing family structure, children need advocates in the political arena as well as in the schools. This pamphlet suggests that administrators are in an excellent position to defend the rights of children on all fronts. It focuses on what administrators have done and specific…

  1. Administration for Student Development.

    ERIC Educational Resources Information Center

    Bergen, J. J., Ed.

    This collection of papers focuses on school administration and its relation to students. It is contended that toay's student matures earlier; has higher expectations; is more affluent; is more isolated from adults; is more critical and outspoken; and, therefore, must be heard by teachers and administrators. A related document is EA 001578.…

  2. Administration of Computer Resources.

    ERIC Educational Resources Information Center

    Franklin, Gene F.

    Computing at Stanford University has, until recently, been performed at one of five facilities. The Stanford hospital operates an IBM 370/135 mainly for administrative use. The university business office has an IBM 370/145 for its administrative needs and support of the medical clinic. Under the supervision of the Stanford Computation Center are…

  3. Rural Administrative Leadership Handbook.

    ERIC Educational Resources Information Center

    Tift, Carolyn

    This resource book on rural administrative leadership is the result of 1988 interviews with school administrators involved in successful rural educational programs. The material is divided into eight chapters, each self-contained for separate use. Chapter 1, "Getting to Know the Community," addresses qualities of living and working in rural…

  4. School Business Administration.

    ERIC Educational Resources Information Center

    Jordan, K. Forbis; Webb, L. Dean

    1986-01-01

    Reviews the societal and organizational changes affecting school business administration, describes major activities encompassed in the practice of school business administration, and reviews current literature specifically related to such activities as electronic data processing, fiscal planning and budgeting, purchasing and property management,…

  5. The Administrative Team.

    ERIC Educational Resources Information Center

    Ohio Association of Elementary School Principals, Westerville.

    Although needs of school districts vary with size, degree of teacher negotiation procedures, and type of community involvement, the administrative team model is presented as an effective, appropriate administrative organization. Based on an assumption that each level of authority in a school district possesses and exercises expertise and unique…

  6. Handbook for Alumni Administration.

    ERIC Educational Resources Information Center

    Webb, Charles H., Ed.

    A definitive look at the field of alumni administration is presented, noting that the subject has until now received little attention. The 34 chapters are divided into nine sections: an overview of alumni administration; alumni as an essential resource; people management; budget and records; programming; communications; alumni education programs…

  7. 47 CFR 54.715 - Administrative expenses of the Administrator.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Administrative expenses of the Administrator. 54.715 Section 54.715 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Administration § 54.715 Administrative expenses of the Administrator. (a) The annual administrative expenses...

  8. 47 CFR 54.715 - Administrative expenses of the Administrator.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Administrative expenses of the Administrator. 54.715 Section 54.715 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Administration § 54.715 Administrative expenses of the Administrator. (a) The annual administrative expenses...

  9. Head of Administration

    NASA Astrophysics Data System (ADS)

    2005-03-01

    Purpose and scope of the position: The main task is to provide efficient administrative services and advice to the Director General, Division Leaders and to staff members in the scientific and technical areas in the fields of financial planning and accounting, personnel management, purchasing, legal and contractual matters, information systems and building and site maintenance. As a member of the ESO Management the Head of Administration contributes essentially to the development of the overall policy, strategic planning, relations to the members of the personnel and maintains professional contacts at highest level outside the Organisation. ESO employs in total approximately 650 staff members and the Administration Division comprises the Administration at the Headquarters in Garching near Munich and the Administration in Santiago (Chile). The successful candidate will be supported by some 50 qualified staff members.

  10. Serving the Space Administration

    ERIC Educational Resources Information Center

    Campbell, Jack E.; Thompson, Arthur W.

    1974-01-01

    The purpose of the current program was to establish an upward mobility program that afforded employees an opportunity to improve their credibility in job opportunity selection under the directives of the National Aeronautics and Space Administration. (Author/RK)

  11. Copyright Implications for Administrators.

    ERIC Educational Resources Information Center

    Simpson, Carol Mann

    1994-01-01

    Discusses copyright compliance policies for school administrators and the librarian's role in policy implementation. Topics addressed include fines; court litigation; monitoring compliance; training sessions for teachers and staff; computer software audits; and sources for more information. (LRW)

  12. Goldstone (GDSCC) administrative computing

    NASA Technical Reports Server (NTRS)

    Martin, H.

    1981-01-01

    The GDSCC Data Processing Unit provides various administrative computing services for Goldstone. Those activities, including finance, manpower and station utilization, deep-space station scheduling and engineering change order (ECO) control are discussed.

  13. Confrontation and Administrative Response

    ERIC Educational Resources Information Center

    Auerbach, Arnold J.

    1969-01-01

    Describes some of the sociological and psychological effects of organizational conflict and offers 10 operational principles to guide public administrators of schools and social agencies in meeting the confrontation tactics of activist groups. (JH)

  14. One for the Administrators

    ERIC Educational Resources Information Center

    American School and University, 1978

    1978-01-01

    Earth berms, a heavily insulated roof, and a narrow band of thermal pane windows, save energy at the administrative headquarters of the Anoka Hennepin school district in Coon Rapids, a suburb of Minneapolis, Minnesota. (Author/MLF)

  15. The Purchasing Administrator.

    ERIC Educational Resources Information Center

    Ferguson, Joyce E.

    1985-01-01

    Discusses the professional purchasing administrator's most common areas of responsibility: (1) staffing the department, (2) maintaining professional objectivity in vendor relationships, (3) following bidding policies, (4) receiving user input and feedback, and (5) seeking local equipment service and maintenance. (MLF)

  16. Introducing Public Administration

    ERIC Educational Resources Information Center

    Stein, Jay W.

    1975-01-01

    The use of documents and the analysis of definitions are recommended as a means for adding zest to an introduction to public administration course to obtain student interest and motivation. (Author/ND)

  17. The sources of foreign policy: The Carter administration and NATO nuclear forces, 1977-80

    SciTech Connect

    Auger, V.A.

    1990-01-01

    The Carter administration entered office committed to the goal of reducing the United States; dependence on nuclear weaponry. This was especially clear in the administration's initial policy towards NATO and the defense of Western Europe. In retrospect, however, what is striking is the degree to which nuclear forces and strategy dominated the Carter administration's policymaking efforts regarding NATO. Decisions about enhanced radiation warheads (or neutron bombs) and long-range theater nuclear forces (ground-launched cruise missiles and Pershing 2 ballistic missiles) created divisions within the alliance and complicated the administration's attempts to control domestic debate over its foreign and defense policies. How did this reversal of emphasis occur Most examinations of this policy change have focused on the existence of a new Soviet threat to Europe or the alliance politics of NATO to explain the dramatic turnabout in American policy. This thesis argues that a close examination of US domestic political factors significantly enhances our understanding of why the Carter administration arrived at the policy decisions it made concerning US theater nuclear forces in Europe.

  18. Anti-cancer activity of bromelain nanoparticles by oral administration.

    PubMed

    Bhatnagar, Priyanka; Patnaik, Soma; Srivastava, Amit K; Mudiam, Mohan K R; Shukla, Yogeshwer; Panda, Amulya K; Pant, Aditya B; Kumar, Pradeep; Gupta, Kailash C

    2014-12-01

    Oral administration of anti-cancer drugs is an effective alternative to improve their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an effective anti-cancer phyto-therapeutic agent, however, its activity is reduced upon oral administration. In addressing the issue, BL was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further, the NPs were coated with Eudragit L30D polymer to introduce stability against the gastric acidic conditions. The resultant coated NPs were characterized for BL entrapment, proteolytic activity and mean particle size. The stability and release pattern of NPs were evaluated under simulated gastrointestinal tract (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of diverse origin have shown significant dose advantage (-7-10 folds) with NPs in reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF-7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as compared to free BL. Altered expression of marker proteins associated with apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti-carcinogenic potential of formulated NPs. Oral administration of NPs reduced the tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also increased their life-span (160.0 ± 5.8%) when compared with free BL (24 ± 3.2%). The generation of reactive oxygen species, induction of apoptosis and impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed the suitability of Eudragit coated BL-NPs as a promising candidate for oral chemotherapy. PMID:26000370

  19. Development, Validation, and Potential Enhancements to the Second-Generation Operational Aerosol Product at the National Environmental Satellite, Data, and Information Service of the National Oceanic and Atmospheric Administration

    NASA Technical Reports Server (NTRS)

    Stowe, Larry L.; Ignatov, Alexander M.; Singh, Ramdas R.

    1997-01-01

    A revised (phase 2) single-channel algorithm for aerosol optical thickness, tau(sup A)(sub SAT), retrieval over oceans from radiances in channel 1 (0.63 microns) of the Advanced Very High Resolution Radiometer (AVHRR) has been implemented at the National Oceanic and Atmospheric Administration's National Environmental Satellite Data and Information Service for the NOAA 14 satellite launched December 30, 1994. It is based on careful validation of its operational predecessor (phase 1 algorithm), implemented for NOAA 14 in 1989. Both algorithms scale the upward satellite radiances in cloud-free conditions to aerosol optical thickness using an updated radiative transfer model of the ocean and atmosphere. Application of the phase 2 algorithm to three matchup Sun-photometer and satellite data sets, one with NOAA 9 in 1988 and two with NOAA 11 in 1989 and 1991, respectively, show systematic error is less than 10%, with a random error of sigma(sub tau) approx. equal 0.04. First results of tau(sup A)(sub SAT) retrievals from NOAA 14 using the phase 2 algorithm, and from checking its internal consistency, are presented. The potential two-channel (phase 3) algorithm for the retrieval of an aerosol size parameter, such as the Junge size distribution exponent, by adding either channel 2 (0.83 microns) from the current AVHRR instrument, or a 1.6-microns channel to be available on the Tropical Rainfall Measurement Mission and the NOAA-KLM satellites by 1997 is under investigation. The possibility of using this additional information in the retrieval of a more accurate estimate of aerosol optical thickness is being explored.

  20. 9. SITE MAP HIGHLIGHTING SIGNIFICANT BUILDINGS AND SHOWING LOCATION LOCATION ...

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

    9. SITE MAP HIGHLIGHTING SIGNIFICANT BUILDINGS AND SHOWING LOCATION LOCATION OF OUTPATIENT CLINIC ADDITION - U.S. Veterans Administration Medical Center, 600 South Seventieth Street, Lincoln, Lancaster County, NE

  1. Astronaut Administrator Richard Truly

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Astronaut Richard H. Truly, pilot of the Space Shuttle Columbia on mission STS-2 and Commander of Shuttle Challenger on mission STS-8, became NASA's eighth Administrator on July 1, 1989. One day earlier he concluded a 30 year Naval career retiring as a Vice Admiral. He was the first astronaut to head the nation's civilian space agency. Truly became Deputy Associate Administrator for Space Flight on February 20, 1986. In this position, he led the painstaking rebuilding of the Space Shuttle program less than one month after the Challenger disaster. This was highlighted by the much heralded 'Return to Flight' on September 29, 1988 with the launch of Shuttle Discovery, 32 months after Challenger's final flight. On February 12th, 1992 Richard Truly resigned as NASA Administrator at the request of President George Bush.

  2. Withdrawal from chronic cocaine administration induces deficits in brain reward function in C57BL/6J mice.

    PubMed

    Stoker, Astrid K; Markou, Athina

    2011-09-30

    Anhedonia is a major symptom of cocaine withdrawal, whereas euphoria characterizes the effects of acute administration of this drug in humans. These mood states can be measured quantitatively in animals with brain reward thresholds obtained from the intracranial self-stimulation (ICSS) procedure. Studies have previously reported the reward-enhancing effects of acute cocaine administration using the ICSS procedure in mice, but the effects of chronic cocaine administration and withdrawal on brain reward thresholds have not been widely investigated in this species. Cocaine withdrawal was induced in C57BL/6J mice by removal of intraperitoneal osmotic minipumps that delivered cocaine (90 or 180 mg/kg/day, salt) for 72 h. Mice were tested in the ICSS procedure 3-100 h post-pump removal. Anxiety-like behavior was assessed in the light-dark box 24h post-pump removal. After an 18-day washout period, tolerance and sensitization to the reward-enhancing effects of cocaine were assessed by injecting bolus cocaine intraperitoneally (0, 2.5, 5, and 10 mg/kg). The results indicated that 72 h administration of 90 and 180 mg/kg/day cocaine significantly lowered brain reward thresholds. Withdrawal from 90 and 180 mg/kg/day of cocaine administration elevated ICSS thresholds to similar extents. No anxiety-like behavior was observed in the light-dark box during withdrawal from chronic cocaine administration, although the number of transitions between compartments and locomotion in the dark compartment markedly decreased. Chronic cocaine administration did not induce tolerance or sensitization to the reward-enhancing effects of acute cocaine. In conclusion, alterations in mood states induced by cocaine administration and withdrawal in mice can be measured using the ICSS procedure. PMID:21557971

  3. The Administrative Role in the Integration of Technology.

    ERIC Educational Resources Information Center

    Ritchie, Donn

    1996-01-01

    Despite technologies' great potential for enhancing classroom instruction and school administration, most schools have yet to implement them beyond a basic level. There are several reasons for this reluctance, including lack of administrative support. Principals must reeducate themselves, procure necessary resources, understand technological…

  4. 36 CFR 230.34 - State program administration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false State program administration. 230.34 Section 230.34 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE STATE AND PRIVATE FORESTRY ASSISTANCE Forest Land Enhancement Program § 230.34 State program administration. (a) In States electing to participate...

  5. 36 CFR 230.34 - State program administration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 2 2014-07-01 2014-07-01 false State program administration. 230.34 Section 230.34 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE STATE AND PRIVATE FORESTRY ASSISTANCE Forest Land Enhancement Program § 230.34 State program administration. (a) In States electing to participate...

  6. Strengthening Collaborative Leadership for Thai Primary School Administrators

    ERIC Educational Resources Information Center

    Samriangjit, Prapaporn; Tesaputa, Kowat; Somprach, Kanokorn

    2016-01-01

    The objectives of this research were: 1) to investigate the elements and indicators of collaborative leadership of primary school administrators, 2) to explore the existing situation and required situation of collaborative leadership of primary school administrators, 3) to develop a program to enhance collaborative leadership of primary school…

  7. Computer hardware fault administration

    DOEpatents

    Archer, Charles J.; Megerian, Mark G.; Ratterman, Joseph D.; Smith, Brian E.

    2010-09-14

    Computer hardware fault administration carried out in a parallel computer, where the parallel computer includes a plurality of compute nodes. The compute nodes are coupled for data communications by at least two independent data communications networks, where each data communications network includes data communications links connected to the compute nodes. Typical embodiments carry out hardware fault administration by identifying a location of a defective link in the first data communications network of the parallel computer and routing communications data around the defective link through the second data communications network of the parallel computer.

  8. MCS Systems Administration Toolkit

    2001-09-30

    This package contains a number of systems administration utilities to assist a team of system administrators in managing a computer environment by automating routine tasks and centralizing information. Included are utilities to help install software on a network of computers and programs to make an image of a disk drive, to manage and distribute configuration files for a number of systems, and to run self-testss on systems, as well as an example of using amore » database to manage host information and various utilities.« less

  9. Caffeine potentiates the enhancement by choline of striatal acetylcholine release

    NASA Technical Reports Server (NTRS)

    Johnson, D. A.; Ulus, I. H.; Wurtman, R. J.

    1992-01-01

    We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.

  10. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b(+) myeloid cells to the lungs and facilitates B16-F10 melanoma colonization.

    PubMed

    Souza, Lucas E B; Almeida, Danilo C; Yaochite, Juliana N U; Covas, Dimas T; Fontes, Aparecida M

    2016-07-15

    The discovery that the regenerative properties of bone marrow multipotent mesenchymal stromal cells (BM-MSCs) could collaterally favor neoplastic progression has led to a great interest in the function of these cells in tumors. However, the effect of BM-MSCs on colonization, a rate-limiting step of the metastatic cascade, is unknown. In this study, we investigated the effect of BM-MSCs on metastatic outgrowth of B16-F10 melanoma cells. In in vitro experiments, direct co-culture assays demonstrated that BM-MSCs stimulated the proliferation of B16-F10 cells in a dose-dependent manner. For in vivo experiments, luciferase-expressing B16-F10 cells were injected through tail vein and mice were subsequently treated with four systemic injections of BM-MSCs. In vivo bioluminescent imaging during 16 days demonstrated that BM-MSCs enhanced the colonization of lungs by B16-F10 cells, which correlated with a 2-fold increase in the number of metastatic foci. Flow cytometry analysis of lungs demonstrated that although mice harboring B16-F10 metastases displayed more endothelial cells, CD4 T and CD8 T lymphocytes in the lungs in comparison to metastases-free mice, BM-MSCs did not alter the number of these cells. Interestingly, BM-MSCs inoculation resulted in a 2-fold increase in the number of CD11b(+) myeloid cells in the lungs of melanoma-bearing animals, a cell population previously described to organize "premetastatic niches" in experimental models. These findings indicate that BM-MSCs provide support to B16-F10 cells to overcome the constraints that limit metastatic outgrowth and that these effects might involve the interplay between BM-MSCs, CD11b(+) myeloid cells and tumor cells. PMID:26027946

  11. Disinfection practices in intravenous drug administration.

    PubMed

    Helder, Onno K; Kornelisse, René F; Reiss, Irwin K M; Ista, Erwin

    2016-06-01

    The aim of the study was to determine the effectiveness of a feedback intervention on adherence to disinfection procedures during intravenous medication preparation and administration. We found that full adherence to the protocols significantly improved from 7.3% to 21.5% (P < .001) regarding medication preparation and from 7.9% to 15.5% (P = .012) regarding medication administration. However, disinfection practices still need improvement. PMID:26899528

  12. Telecommunications administration standard

    SciTech Connect

    Gustwiller, K.D.

    1996-05-01

    The administration of telecommunications is critical to proper maintenance and operation. The intent is to be able to properly support telecommunications for the distribution of all information within a building/campus. This standard will provide a uniform administration scheme that is independent of applications, and will establish guidelines for owners, installers, designers and contractors. This standard will accommodate existing building wiring, new building wiring and outside plant wiring. Existing buildings may not readily adapt to all applications of this standard, but the requirement for telecommunications administration is applicable to all buildings. Administration of the telecommunications infrastructure includes documentation (labels, records, drawings, reports, and work orders) of cables, termination hardware, patching and cross-connect facilities, telecommunications rooms, and other telecommunications spaces (conduits, grounding, and cable pathways are documented by Facilities Engineering). The investment in properly documenting telecommunications is a worthwhile effort. It is necessary to adhere to these standards to ensure quality and efficiency for the operation and maintenance of the telecommunications infrastructure for Sandia National Laboratories.

  13. Study Shows Administrative Shortage.

    ERIC Educational Resources Information Center

    Sullivan, John R., Jr.

    1989-01-01

    Summarizes "Administrative Shortage in New England: The Evidence, the Causes, the Recommendations." High pressure, long hours, low salaries, and high housing costs are among the reasons cited for the shortage. Recommendations are centered on role identity, staff support, training, and recruitment. (SI)

  14. Central Administration. Interim Report.

    ERIC Educational Resources Information Center

    Duke Univ., Durham, NC.

    Because the configuration of the central administration of Duke University has recently been modified, this report was prepared: (1) to describe the changes and rearrangements thus far introduced; (2) to propose desirable clarifications not yet provided; (3) to recommend certain additional changes where these may already appear to be needed; and…

  15. Guidebook for School Administrators.

    ERIC Educational Resources Information Center

    Hess, Fritz, Ed.

    To provide guidance and advice regarding day-to-day responsibilities of new and experienced school administrators and superintendents in New York State, this compendium of knowledge and advice submitted by practitioners is presented with emphasis on all major aspects of superintendency. The section on general aspects of superintendency includes…

  16. Redis database administration tool

    2013-02-13

    MyRedis is a product of the Lorenz subproject under the ASC Scirntific Data Management effort. MyRedis is a web based utility designed to allow easy administration of instances of Redis databases. It can be usedd to view and manipulate data as well as run commands directly against a variety of different Redis hosts.

  17. Female Administrator Acceptance.

    ERIC Educational Resources Information Center

    Pawlitschek, Elizabeth Ann

    The number of women in educational administration is declining, despite official efforts to end sex discrimination. Women are hampered on the way to obtaining an adequate education, finding roadblocks from sex bias in elementary readers to discrimination in graduate programs; are considered responsible for home and children even when working full…

  18. Hospital Library Administration.

    ERIC Educational Resources Information Center

    Cramer, Anne

    The objectives of a hospital are to improve patient care, while the objectives of a hospital library are to improve services to the staff which will support their efforts. This handbook dealing with hospital administration is designed to aid the librarian in either implementing a hospital library, or improving services in an existing medical…

  19. Discretionary Grants Administration Manual.

    ERIC Educational Resources Information Center

    Office of Human Development Services (DHHS), Washington, DC.

    This manual sets forth applicable administrative policies and procedures to recipients of discretionary project grants or cooperative agreements awarded by program offices in the Office of Human Development Services (HDS). It is intended to serve as a basic reference for project directors and business officers of recipient organizations who are…

  20. [Rural School Administrator's Resources.

    ERIC Educational Resources Information Center

    AEL, Inc., Charleston, WV.

    This packet contains resources on five topics relevant to rural school administrators. "Assessing Parent Involvement: A Checklist for Rural Schools": discusses educator beliefs that support successful parent engagement programs, challenges and advantages of rural schools attempting to involve parents and community, and aspects of successful…

  1. Information for School Administrators.

    ERIC Educational Resources Information Center

    Kowitz, Gerald T.; And Others

    Modern management theory, based on the reduction of uncertainties, demands the collection and manipulation of large amounts of information. School Administrators choke in the process of trying to digest a proliferation of data, only some of which are useful. The aims of the study were to explore the extent to which large amounts of data could be…

  2. Research Administration: Lessons Learned.

    ERIC Educational Resources Information Center

    Dummer, George H.

    1995-01-01

    The ways in which accountability issues have affected federal-university relationships, particularly in the area of academic research, are examined. Lessons university administrators have learned since issuance of Office of Management and Budget Circular A-21 in 1958, Congressional hearings on the operations of the National Institutes of Health…

  3. Administrators Confront Student "Sexting"

    ERIC Educational Resources Information Center

    Manzo, Kathleen Kennedy

    2009-01-01

    Cellphone-savvy students have created instructional and disciplinary challenges for educators for years. But the recent emergence of "sexting" by adolescents over their mobile phones caught many school administrators off guard, and the practice is prompting efforts around the country to craft policy responses. Students' sharing of nude or…

  4. Championing the Latino Administrator

    ERIC Educational Resources Information Center

    Garcia, Carlos A.

    2011-01-01

    When the author worked as a vice principal at a K-8 school in Watsonville, California, a school predominantly filled with migrant workers' children, he felt a lack of support as a Latino as he began moving up into school administration. He also continued to see what he had seen as a teacher--which was how underserved minority students were. These…

  5. Hispanic Administrators in Kentucky

    ERIC Educational Resources Information Center

    Ballestero, Victor; Wright, Sam

    2008-01-01

    The study was designed to provide information on Hispanic administrators in the Commonwealth of Kentucky. The data was obtained from Kentucky school Superintendents or their designees in 175 public school districts. The Hispanic survey contained six questions. The survey was mailed to Kentucky Superintendents on April 21, 2008. A follow-up survey…

  6. Educational Administration's Weber.

    ERIC Educational Resources Information Center

    Gronn, Peter

    1994-01-01

    Discusses Max Weber's importance in Greenfield's work, particularly in Greenfield and Ribbins'"Greenfield on Educational Administration" (1993). In concentrating on human actors' subjective understanding, Greenfield was a faithful Weberian. However, he deviated from Weber by disavowing structural explanations of social and organizational…

  7. "Complicating" Educational Administrators.

    ERIC Educational Resources Information Center

    Bell, Colleen S.

    Administrators desiring to lead organizations that will adapt and survive in a complex environment like today's public schools need to develop what Karl Weick calls "complicated" understanding of "requisite variety." The law of requisite variety states that a diverse and complicated environment demands similar diversity from its inhabitants if…

  8. A Treatise on Administration.

    ERIC Educational Resources Information Center

    Moore, Thomas R.

    1988-01-01

    Expands Henri Fayol's definition of the administrative process to include a humanistic approach involving planning, organizing, implementing, controlling, evaluating, and satisfying functions. This empirical definition differs from some theoretical approaches by looking beyond resource consumption to consider ecological effects on the environment…

  9. Administrative Uses of Microcomputers.

    ERIC Educational Resources Information Center

    Crawford, Chase

    1987-01-01

    This paper examines the administrative uses of the microcomputer, stating that high performance educational managers are likely to have microcomputers in their organizations. Four situations that would justify the use of a computer are: (1) when massive amounts of data are processed through well-defined operations; (2) when data processing is…

  10. Administrative Utility Analysis: Appendices.

    ERIC Educational Resources Information Center

    Peat, Marwick, Mitchell and Co., San Juan, Puerto Rico.

    Appendixes to a study on administrative utility analysis and vocational education programs for the Area of Vocational and Technical Education (AVTE) in the Puerto Rico Department of Education contain the planning and budgeting system elements, position descriptions, and information on the growth of vocational education in Puerto Rico. The elements…

  11. Educator Effectiveness Administrative Manual

    ERIC Educational Resources Information Center

    Pennsylvania Department of Education, 2014

    2014-01-01

    The goal of this manual is to provide guidance in the evaluation of educators, highlight critical components of effectiveness training, and offer opportunities for professional growth. The term "educator" includes teachers, all professional and temporary professional employees, education specialists, and school administrators/principals.…

  12. Standards and Administration.

    ERIC Educational Resources Information Center

    Gross, S. P.

    1978-01-01

    Presents a literature review of water quality standards and administration, covering publications of 1976-77. Consideration is given to municipal facilities, National Pollutant Discharge Elimination Systems, regional and international water quality management, and effluent standards. A list of 99 references is also presented. (HM)

  13. Migrant Education Administrative Handbook.

    ERIC Educational Resources Information Center

    Louisiana State Dept. of Education, Baton Rouge. Bureau of Migrant Education.

    Intended to provide information pertaining to the administration of migrant education projects in Louisiana, the handbook is divided into two sections: basic guidelines for program operations and support services--nursing. Section I covers the Federal and State migrant program, local migrant projects, project personnel and staff development, and…

  14. Using Administrative Data. Introduction.

    ERIC Educational Resources Information Center

    DiLeonardi, Joan W.; Yuan, Ying-Ying T.

    2000-01-01

    Discusses the value of administrative data to child welfare researchers. Considers issues in using client records--confidentiality, selection of data, historical data, sampling reliability, replication of findings, and access to data--that can be resolved in standardized ways. Notes other problematic issues, such as greater distance from subject,…

  15. Standards for Administrators.

    ERIC Educational Resources Information Center

    Lashway, Larry

    1998-01-01

    This newsletter reviews five reports that address the implications of standards for administrators. These texts include "Designing and Implementing Standards-Based Accountability System" (Education Commission of the States), which describes some of the policy implications of standards-driven accountability; "Why Principals Fail: Are National…

  16. Encounters with aggressive conspecifics enhance the locomotor-activating effects of cocaine in the rat.

    PubMed

    Marrow, L P; Overton, P G; Brain, P F; Clark, D

    1999-10-01

    Evidence suggests that stress enhances the behavioural actions of cocaine in the rat. Paradoxically, however, encounters with aggressive conspecifics lead to a pattern of cocaine self-administration indicative of a reduced functional impact of the drug. Hence, we examined the effects of aggressive encounters on another behavioural measure-locomotor activity. Encounters between Lister Hooded rats and rats of the aggressive Tryon Maze Dull strain significantly enhanced the locomotor-activating effects of cocaine (20 mg/kg) in the Lister Hooded rats. The results suggest that the discrepant findings derived from self-administration studies are a property of the paradigm rather than a property of the stressor. PMID:20575812

  17. Leadership Behaviors of Vocational Education Administrators in the Midwest.

    ERIC Educational Resources Information Center

    Baugher, Shirley L.; And Others

    1985-01-01

    Leadership behaviors of vocational education administrators in 15 midwestern states were studied. The administrators, representing four institutional types, responded to Part LB of the Boss' Management Styles Survey and the Bem Sex Role Inventory. The MANOVA procedure revealed statistically significant differences among administrative roles with…

  18. INTRAARTERIAL INJECTION OF IODINATED CONTRAST MEDIUM FOR CONTRAST ENHANCED COMPUTED TOMOGRAPHY OF THE EQUINE HEAD.

    PubMed

    Carmalt, James L; Montgomery, James

    2015-01-01

    Minimizing the volume of contrast administered for contrast-enhanced computed tomography (CT) of the equine head is desirable for reducing costs and risks of adverse reactions, however evidence-based studies on the effects of varying volumes on image quality are currently lacking. The objective of the current study was to determine whether low-volume intraarterial administration of contrast medium would result in an equivalent image quality and tissue attenuation vs. high-volume intravenous bolus administration. A prospective cross-over experimental design was used in a sample of six horses. After anesthetic induction, the right carotid artery was exposed surgically and catheterized. Four CT scans of the cranium were performed for each horse: baseline, immediately following intraarterial contrast injection, five-min postinjection (return to baseline) and a final scan after intravenous contrast administration. Soft tissue attenuation in predetermined regions of interest (ROI); and length, width, and height measurements of the pituitary gland were recorded at each time point. Horses were euthanized and measurements of the pituitary gland were repeated postmortem. No adverse reactions to contrast administration were observed. Intraarterial and intravenous administration of contrast medium resulted in significantly greater soft tissue enhancement of some brain ROI's and the pituitary gland vs. baseline values. Pituitary gland measurements made on postcontrast CT images did not differ from those obtained during postmortem examination. Findings indicated that low-dose intraarterial administration of contrast material in the equine head resulted in comparable soft tissue enhancement vs. high volume intravenous administration. PMID:25782997

  19. Developing Psychic Income in School Administration: The Unique Role School Administrators Can Play

    ERIC Educational Resources Information Center

    Guramatunhu-Mudiwa, Precious; Scherz, Susan Day

    2013-01-01

    This concept article discusses the importance of developing psychic income as an administrative strategy to enhance the context of school environments and to curb high teacher turnover. The hope is to promote further debate and research in order to establish the extent to which psychic income influences retention rates in hard-to-staff schools.…

  20. One-Year Outcomes of Out-of-Hospital Administration of Intravenous Glucose, Insulin, and Potassium (GIK) in Patients with Suspected Acute Coronary Syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care] Trial)

    PubMed Central

    Selker, Harry P.; Udelson, James E.; Massaro, Joseph M.; Ruthazer, Robin; D’Agostino, Ralph B.; Griffith, John L.; Sheehan, Patricia R.; Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin; Vickery, Ellen M.; Atkins, James M.; Aufderheide, Tom P.; Sayah, Assaad J.; Pirrallo, Ronald G.; Levy, Michael K.; Richards, Michael E.; Braude, Darren A.; Doyle, Delanor D.; Frascone, Ralph J.; Kosiak, Donald J.; Leaming, James M.; Van Gelder, Carin M.; Walter, Gert-Paul; Wayne, Marvin A.; Woolard, Robert H.; Beshansky, Joni R.

    2014-01-01

    The IMMEDIATE Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefit. Here we report 1-year outcomes. Pre-specified 1-year endpoints of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality, and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Among 871 participants randomized to GIK vs. placebo, respectively, death occurred within 1 year in 11.6% vs. 13.5% (unadjusted hazard ratio [HR] 0.83; 95% CI 0.57, 1.23, P=0.36). The composite of cardiac arrest or 1-year mortality was 12.8% vs. 17.0% (HR 0.71; 95% CI 0.50, 1.02, P=0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% vs. 17.2% (HR 0.98; 95% CI 0.70, 1.37, P=0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% vs. 20.4% (HR 0.85; 95% CI 0.62, 1.16, P=0.30). Among patients presenting with suspected ST elevation myocardial infarction (STEMI), hazard ratios for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33, 1.27, P=0.21); 0.52 (95% CI 0.30, 0.92, P=0.03); 0.63 (95% CI 0.35, 1.16, P=0.14); and 0.51 (95% CI 0.30, 0.87, P=0.01). Among patients with suspected ACS, serious endpoints generally were lower with GIK than placebo, but the differences were not statistically significant. However, among those with STEMI, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced. PMID:24792735

  1. Ethosomes as delivery system for transdermal administration of vinpocetine.

    PubMed

    Mao, Yan-Ting; Hua, Hai-Ying; Zhang, Xiang-Guo; Zhu, Dong-Xue; Li, Feng; Gui, Zhen-Hua; Zhao, Yong-Xing

    2013-05-01

    The purpose of the present study was to develop a novel transdermal vinpocetine patch containing a stable formulation and with good entrapment efficiency, and percutaneous absorption which via ethosome. Ethosome was found to be a more efficient delivery carrier with high encapsulation capacities (79.5% +/- 1.8%) and nanometric size (180.7 +/- 1.5 nm). In vitro percutaneous permeation experiments demonstrated that the permeation of vinpocetine through abdominal skin of Sprague Dawley was significantly increased when ethosome was used. The vinpocetine transdermal fluxes from ethosome gel (3.56 +/- 0.13 microg/cm2/h) were 6.72 and 3.10 times higher than that of vinpocetine gel solution and vinpocetine aueous solution, respectively. Furthermore, the AUC(0 --> infinity), and eliminiation half-life by the transdermal administration were significantly higher than those by the intragastric administration (P < 0.01). The study demonstrated that ethosome is a promising vesicular carrier for enhancing percutaneous absorption of vinpocetine. PMID:23802438

  2. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... IRANIAN FINANCIAL SANCTIONS REGULATIONS General Definitions § 561.328 Reduce significantly,...

  3. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... IRANIAN FINANCIAL SANCTIONS REGULATIONS General Definitions § 561.328 Reduce significantly,...

  4. "Clinical" Significance: "Clinical" Significance and "Practical" Significance are NOT the Same Things

    ERIC Educational Resources Information Center

    Peterson, Lisa S.

    2008-01-01

    Clinical significance is an important concept in research, particularly in education and the social sciences. The present article first compares clinical significance to other measures of "significance" in statistics. The major methods used to determine clinical significance are explained and the strengths and weaknesses of clinical significance…

  5. 7. Administrative structures.

    PubMed

    2014-05-01

    The basic systems of any society rarely can operate independently. Instead, they are dependent and often interdependent upon other entities. Such entities control the resources within their respective systems. Thus, coordination and control agencies require contracts or memoranda of understanding with these entities in order to assure access to the resources required during a crisis. These administrative structures include: (1) governmental institutions and agencies, including the military; (2) intergovernmental organisations; (3) nongovernmental organisations; (4) commercial private sector organisations; and (5) academic institutions. These dependencies create potential barriers to the provision of coordination and control including: (1) the complexity of the administrative structures with which coordination and control must interact; (2) the location of resources; (3) finding responsible person(s); (4) the competence and compatibility; (5) methods of access; (6) payment; (7) contracts and memoranda of understanding; (8) inventories of accessible resources; (9) competition for the mandate, power, and resources; and (10) jealousy. The need for potential interactions between administrative structures requires that agreements for the sharing of resources during crises be reached as part of planning and preparedness. Gaining an understanding of these relationships is an important area for research. PMID:24785804

  6. Enhanced preliminary assessment

    SciTech Connect

    Not Available

    1992-02-01

    An Enhanced Preliminary Assessment was conducted at Fort Benjamin Harrison (FBH) Indiana, which is located approximately 12 miles from downtown Indianapolis in Lawrence Township, Marion County. FBH contains 2,501 acres, of which approximately 1,069 acres is covered by woodlands. Activities at FBH include administration, training, housing, and support. Sensitive environments at FBH include wetlands, habitat areas for the endangered Indiana bat, endangered plants, and historically and archeologically significant areas. FBH is a U.S. Army Soldier Support Center under the jurisdiction of the U.S. Army Training and Doctrine Command (TRADOC). Based on information obtained during and subsequent to a site visit (15 through 18 October 1991), 36 types of Areas Requiring Environmental Evaluation (AREEs) were identified and grouped by the following categories: Facility Operations; Maintenance/Fueling Operations; Water Treatment Operations; Training Areas; Hazardous Materials Storage/Waste Handling Areas; Sanitary Wastewater Treatment Plants; Storage Tanks; Landfills/Incinerators; Medical Facilities; Burn Pit Areas; Spill Areas; Ammunition Storage; Coal Storage; and Facility-wide AREEs. This report presents a summary of findings for each AREE and recommendations for further action.

  7. Glucocorticoids enhance extinction-based psychotherapy

    PubMed Central

    de Quervain, Dominique J.-F.; Bentz, Dorothée; Michael, Tanja; Bolt, Olivia C.; Wiederhold, Brenda K.; Margraf, Jürgen; Wilhelm, Frank H.

    2011-01-01

    Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction. Because preclinical studies have shown that glucocorticoids can promote extinction processes, we aimed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy. In a randomized, double-blind, placebo-controlled study, 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights. Cortisol (20 mg) or placebo was administered orally 1 h before each of the treatment sessions. Subjects returned for a posttreatment assessment 3–5 d after the last treatment session and for a follow-up assessment after 1 mo. Adding cortisol to exposure therapy resulted in a significantly greater reduction in fear of heights as measured with the acrophobia questionnaire (AQ) both at posttreatment and at follow-up, compared with placebo. Furthermore, subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up. The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy. PMID:21444799

  8. Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps

    PubMed Central

    Kayiran, Oguz; Cuzdan, Suat S.; Uysal, Afsin; Kocer, Ugur

    2013-01-01

    Introduction: Numerous pharmacological agents have been used to enhance the viability of flaps. Ischemia reperfusion (I/R) injury is an unwanted, sometimes devastating complication in reconstructive microsurgery. Tadalafil, a specific inhibitor of phosphodiesterase type 5 is mainly used for erectile dysfunction, and acts on vascular smooth muscles, platelets and leukocytes. Herein, the protective and therapeutical effect of tadalafil in I/R injury in rat skin flap model is evaluated. Materials and Methods: Sixty epigastric island flaps were used to create I/R model in 60 Wistar rats (non-ischemic group, ischemic group, medication group). Biochemical markers including total nitrite, malondialdehyde (MDA) and myeloperoxidase (MPO) were analysed. Necrosis rates were calculated and histopathologic evaluation was carried out. Results: MDA, MPO and total nitrite values were found elevated in the ischemic group, however there was an evident drop in the medication group. Histological results revealed that early inflammatory findings (oedema, neutrophil infiltration, necrosis rate) were observed lower with tadalafil administration. Moreover, statistical significance (P < 0.05) was recorded. Conclusions: We conclude that tadalafil has beneficial effects on epigastric island flaps against I/R injury. PMID:23960309

  9. Did the corporatization of Portuguese hospitals significantly change their productivity?

    PubMed

    Ferreira, Diogo; Marques, Rui Cunha

    2015-04-01

    This paper aims to investigate if the market structure reforms in the Portuguese health system have improved hospital performance and productivity. A robust non-parametric Malmquist index is applied to measure group performance. The significance of the results achieved is examined using a conditional and non-conditional subsampling bootstrapped-based methodology, enhanced by the likelihood cross validation criterion based on the k-nearest neighbors method. The sample contains information about 216 non-corporatized and 176 corporatized Portuguese hospitals for the period 2002–2009. Five models were applied, based on three study dimensions (internment, emergencies and doctor visits). The results show that although corporatized hospitals presented the highest efficiency consistency, they had also the lowest levels of productivity, while the hospitals under the traditional administrative public management system were the ones with the best average performance. However, several best practices were also found in all groups, being the limited companies were often dominated by both noncorporatized and public enterprise entities. Consistent output ranges where all groups present dominance over the others were also identified. It was possible to conclude that the more autonomy the hospital had from the Ministry of Health, the lower was its productivity. PMID:24659018

  10. Astrobiological Significance of Microbial Extremophiles

    NASA Technical Reports Server (NTRS)

    Pikuta, Elena V.; Hoover, Richard B.

    2007-01-01

    The microflora of the cryosphere of planet Earth provides the best analogs for life forms that might be found in the permafrost or polar ice caps of Mars, near the surface of the cometary nuclei, or in the liquid water beneath and the ice crusts of icy moons of Jupiter and Saturn. The importance of study alkaliphilic microorganisms for astrobiology was enhanced by the findings of abundant carbonates and carbonate globules rimmed with possibly biogenic magnetites in association with the putative microfossils in the ALH84001 meteorite. Although the ALH84001 "nanofossils" were to small and simple to be unambiguously recognized as biogenic, they stimulated Astrobiology research and studies of microbial extremophiles and biomarkers in ancient rocks and meteorites. Recent studies of CI and CM carbonaceous meteorites have resulted in the detection of the well-preserved mineralized remains of coccoidal and filamentous microorganisms in cyanobacterial mats. Energy Dispersive X-ray Analysis has shown anomalous biogenic element ratios clearly indicating they are not recent biological contaminants. This paper reviews microbial extremophiles in context of their significance to Astrobiology. The study of halophilic microorganisms was started from work with saline soils and lakes, and one of the record of good growth for Haloferax mediterranei was shown at 30 percent NaC1. Although alkali-tolerant nitrifying bacteria had previously been reported, the first described alkaliphilic microorganism was the bacterium Streptococcus faecalis. Halophilic and alkaliphilic forms are relevant to conditions that might be found in closed impact basins and craters on Mars filled with evaporite deposits. The first obligately acidophilic bacterium described was Acidithiobacillus ferrooxydans (formally Thiobacillus ferrooxidans). Later thermophilic lithotrophic acidophiles were found, and the hyperacidophilic moderately thermophilic species of the genus Picrophilus were found to grow at negative p

  11. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  12. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  13. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  14. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  15. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  16. A Single Oral Administration of Theaflavins Increases Energy Expenditure and the Expression of Metabolic Genes

    PubMed Central

    Kudo, Naoto; Arai, Yasunori; Suhara, Yoshitomo; Ishii, Takeshi; Nakayama, Tsutomu; Osakabe, Naomi

    2015-01-01

    Theaflavins are polyphenols found in black tea, whose physiological activities are not well understood. This study on mice evaluated the influence of a single oral administration of theaflavins on energy metabolism by monitoring the initial metabolic changess in skeletal muscle and brown adipose tissue (BAT). Oxygen consumption (VO2) and energy expenditure (EE) were increased significantly in mice treated with theaflavin rich fraction (TF) compared with the group administered vehicle alone. There was no difference in locomotor activity. Fasting mice were euthanized under anesthesia before and 2 and 5, 20-hr after treatment with TF or vehicle. The mRNA levels of uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in BAT were increased significantly 2-hr after administration ofTF. The levels of UCP-3 and PGC-1α in the gastrocnemius muscle were increased significantly 2 and 5-hr after administration of TF. The concentration of phosphorylated AMP-activated protein kinase (AMPK) 1α was also increased significantly in the gastrocnemius 2 and 5-hr after treatment with TF. These results indicate that TF significantly enhances systemic energy expenditure, as evidenced by an increase in expression of metabolic genes. PMID:26375960

  17. A Single Oral Administration of Theaflavins Increases Energy Expenditure and the Expression of Metabolic Genes.

    PubMed

    Kudo, Naoto; Arai, Yasunori; Suhara, Yoshitomo; Ishii, Takeshi; Nakayama, Tsutomu; Osakabe, Naomi

    2015-01-01

    Theaflavins are polyphenols found in black tea, whose physiological activities are not well understood. This study on mice evaluated the influence of a single oral administration of theaflavins on energy metabolism by monitoring the initial metabolic changess in skeletal muscle and brown adipose tissue (BAT). Oxygen consumption (VO2) and energy expenditure (EE) were increased significantly in mice treated with theaflavin rich fraction (TF) compared with the group administered vehicle alone. There was no difference in locomotor activity. Fasting mice were euthanized under anesthesia before and 2 and 5, 20-hr after treatment with TF or vehicle. The mRNA levels of uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in BAT were increased significantly 2-hr after administration ofTF. The levels of UCP-3 and PGC-1α in the gastrocnemius muscle were increased significantly 2 and 5-hr after administration of TF. The concentration of phosphorylated AMP-activated protein kinase (AMPK) 1α was also increased significantly in the gastrocnemius 2 and 5-hr after treatment with TF. These results indicate that TF significantly enhances systemic energy expenditure, as evidenced by an increase in expression of metabolic genes. PMID:26375960

  18. Handbook of Administrative Supervision.

    ERIC Educational Resources Information Center

    Falvey, Janet Elizabeth

    This handbook is one of four handbooks developed for preservice and inservice counselor preparation and professional development. It was developed as a practical guide which will provide resources for supervisors to use in the field for enhancing their own skills or for use with other counselors under their supervision. It is also appropriate for…

  19. Moral Enhancement

    PubMed Central

    Douglas, Thomas

    2008-01-01

    Opponents of biomedical enhancement often claim that, even if such enhancement would benefit the enhanced, it would harm others. But this objection looks unpersuasive when the enhancement in question is a moral enhancement — an enhancement that will expectably leave the enhanced person with morally better motives than she had previously. In this article I (1) describe one type of psychological alteration that would plausibly qualify as a moral enhancement, (2) argue that we will, in the medium-term future, probably be able to induce such alterations via biomedical intervention, and (3) defend future engagement in such moral enhancements against possible objections. My aim is to present this kind of moral enhancement as a counter-example to the view that biomedical enhancement is always morally impermissible. PMID:19132138

  20. Effect of long-term administration of melatonin on adrenal histomorphology of the Indian desert gerbil Meriones hurrianae Jerdon.

    PubMed

    Joshi, B N; Sujathakumari, M

    1995-11-01

    Melatonin treatment for 8 weeks resulted in a significant increase (P < 0.01) in weights of the adrenal glands, in both male and female, M. hurrianae. The weight increase was not related to the time of administration of melatonin. Histology of adrenal glands in melatonin treated gerbils revealed a stimulatory response. In treated gerbils, adrenal cortex exhibited significant hypertrophy with enlarged nuclei and degranulated cytoplasm. Signs of hypertrophy were also evident in the adrenal medulla. The physiological significance of this response is not yet clear. It remains to be clarified if the hypertrophy indicates enhanced synthesis of corticosteroids. PMID:8786156

  1. Domino System Administration

    NASA Astrophysics Data System (ADS)

    Kirkland, R.

    Need a concise, practical explanation about the new features of Domino, and how to make some of the advanced stuff really work? You need answers and solutions from someone who's been in the trenches. You want information from someone like you, who has worked with the product for years, and understands what it is you need to know. Domino System Administration from New Riders is the answer-the first book on Domino that attacks the technology at the professional level, with practical, hands-on assistance to get Domino 5 running in your organization.

  2. 21 CFR 201.18 - Drugs; significance of control numbers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs; significance of control numbers. 201.18 Section 201.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.18 Drugs; significance of control numbers. The lot number on the label of a...

  3. 49 CFR 1580.105 - Reporting significant security concerns.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Hazardous Materials Receivers, and Private Cars § 1580.105 Reporting significant security concerns. (a... 49 Transportation 9 2012-10-01 2012-10-01 false Reporting significant security concerns. 1580.105... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY MARITIME AND LAND TRANSPORTATION SECURITY...

  4. 49 CFR 1580.105 - Reporting significant security concerns.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Hazardous Materials Receivers, and Private Cars § 1580.105 Reporting significant security concerns. (a... 49 Transportation 9 2014-10-01 2014-10-01 false Reporting significant security concerns. 1580.105... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY MARITIME AND LAND TRANSPORTATION SECURITY...

  5. 49 CFR 1580.105 - Reporting significant security concerns.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Hazardous Materials Receivers, and Private Cars § 1580.105 Reporting significant security concerns. (a... 49 Transportation 9 2013-10-01 2013-10-01 false Reporting significant security concerns. 1580.105... SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY MARITIME AND LAND TRANSPORTATION SECURITY...

  6. 40 CFR 300.323 - Spills of national significance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES POLLUTION CONTINGENCY PLAN Operational Response Phases for Oil Removal § 300.323 Spills of national significance. (a) A discharge may be classified as a spill of national significance (SONS) by the Administrator of EPA...

  7. 40 CFR 300.323 - Spills of national significance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES POLLUTION CONTINGENCY PLAN Operational Response Phases for Oil Removal § 300.323 Spills of national significance. (a) A discharge may be classified as a spill of national significance (SONS) by the Administrator of EPA...

  8. 40 CFR 300.323 - Spills of national significance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES POLLUTION CONTINGENCY PLAN Operational Response Phases for Oil Removal § 300.323 Spills of national significance. (a) A discharge may be classified as a spill of national significance (SONS) by the Administrator of EPA...

  9. 40 CFR 300.323 - Spills of national significance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES POLLUTION CONTINGENCY PLAN Operational Response Phases for Oil Removal § 300.323 Spills of national significance. (a) A discharge may be classified as a spill of national significance (SONS) by the Administrator of EPA...

  10. 31 CFR 561.404 - Significant transaction or transactions; significant financial services; significant financial...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Significant transaction or transactions; significant financial services; significant financial transaction. 561.404 Section 561.404 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY...

  11. A Review of the Literature on College Administrators and Administrations.

    ERIC Educational Resources Information Center

    Nash, George; Uhse, Stefan

    A review of the extensive literature on college administration and college administrators reveals there are relatively few empirical studies in the field. It was also observed that: there is widespread agreement on a few broad principles; there has been a heavy emphasis on human relations and proper administrative procedures; there are fundamental…

  12. Haptoglobin Enhances Cardiac Transplant Rejection

    PubMed Central

    Shen, Hua; Heuzey, Elizabeth; Mori, Daniel; Wong, Christine; Colangelo, Christopher; Chung, Lisa M.; Bruce, Can; Slizovskiy, Ilya B.; Booth, Carmen J.; Kreisel, Daniel; Goldstein, Daniel R.

    2015-01-01

    Rationale Early graft inflammation enhances both acute and chronic rejection of heart transplants, but it is unclear how this inflammation is initiated. Objective To identify specific inflammatory modulators and determine their underlying molecular mechanisms after cardiac transplantation. Methods and Results We used a murine heterotopic cardiac transplant model to identify inflammatory modulators of early graft inflammation. Unbiased mass spectrometric analysis of cardiac tissue before and up to 72 hours after transplantation revealed that 22 proteins including haptoglobin, a known anti-oxidant, are significantly upregulated in our grafts. Through the use of haptoglobin deficient mice, we show that 80% of haptoglobin deficient recipients treated with peri-operative administration of the costimulatory blocking agent CTLA4 immunoglobulin exhibited > 100 days survival of full major histocompatibility complex mismatched allografts, whereas all similarly treated wild type recipients rejected their transplants by 21 days post transplantation. We found that haptoglobin modifies the intra-allograft inflammatory milieu by enhancing levels of the inflammatory cytokine IL-6 and the chemokine MIP-2 but impair levels of the immunosuppressive cytokine IL-10. Haptoglobin also enhances dendritic cell graft recruitment and augments anti-donor T cell responses. Moreover, we confirmed that the protein is present in human cardiac allograft specimens undergoing acute graft rejection. Conclusions Our findings provide new insights into the mechanisms of inflammation after cardiac transplantation and suggest that, in contrast to its prior reported anti-oxidant function in vascular inflammation, haptoglobin is an enhancer of inflammation after cardiac transplantation. Haptoglobin may also be a key component in other sterile inflammatory conditions. PMID:25801896

  13. 21 CFR 10.70 - Documentation of significant decisions in administrative file.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... decision on any matter under the laws administered by the Commissioner, whether it is raised formally, for.... The file must contain: (1) Appropriate documentation of the basis for the decision, including...

  14. 21 CFR 10.70 - Documentation of significant decisions in administrative file.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... decision on any matter under the laws administered by the Commissioner, whether it is raised formally, for.... The file must contain: (1) Appropriate documentation of the basis for the decision, including...

  15. 21 CFR 10.70 - Documentation of significant decisions in administrative file.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... decision on any matter under the laws administered by the Commissioner, whether it is raised formally, for.... The file must contain: (1) Appropriate documentation of the basis for the decision, including...

  16. 21 CFR 10.70 - Documentation of significant decisions in administrative file.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... decision on any matter under the laws administered by the Commissioner, whether it is raised formally, for.... The file must contain: (1) Appropriate documentation of the basis for the decision, including...

  17. Discovery of medically significant lantibiotics.

    PubMed

    Piper, Clare; Cotter, Paul D; Ross, R Paul; Hill, Colin

    2009-03-01

    The emergence of drug-resistant pathogens such as staphylococci and enterococci in the hospital setting has long being recognized as a serious clinical problem. Staphylococcus aureus is the causative agent of many nosocomial infections from minor skin abscesses to serious, potentially life threatening diseases such as bone and soft tissue intra-surgical infections, sepsis and invasive endocarditis, while enterococci are responsible for nosocomial bacteraemia, surgical wound infections and endocarditis. The most infamous drug-resistant forms of these include MRSA (methicillin resistant S. aureus), VISA (vancomycin insensitive S. aureus), hVISA (heterogenous vancomycin insensitive S. aureus) and VRE (vancomycin resistant S. aureus). While enhanced hygiene awareness is essential to any solution, the identification of effective novel antimicrobial compounds remains a major goal in eradicating these and other infections caused by multi-drug resistant pathogens. In recent years a class of antimicrobial peptides, the Lantibiotics, have been the focus of an ever increasing level of attention. This interest has been prompted by an enhanced appreciation of the mode of action of these peptides (including, in many cases, the ability to bind lipid II) and their frequently high levels of antimicrobial activity. Here we review lantibiotic-related issues in drug discovery, outline the strategies that have been employed to identify these peptides and summarize the use of bioengineering to generate enhanced forms of these peptides as well as the application of the associated biological machinery to generate novel forms of existing pharmaceutical compounds. In so doing we highlight how some, or all, of these approaches have the potential to result in the development of clinically important drugs. PMID:19275538

  18. Local Administration of AAV-BDNF to Subventricular Zone Induces Functional Recovery in Stroke Rats

    PubMed Central

    Yu, Seong-Jin; Tseng, Kuan-Yin; Shen, Hui; Harvey, Brandon K.; Airavaara, Mikko; Wang, Yun

    2013-01-01

    Migration of new neuroprogenitor cells (NPCs) from the subventricular zone (SVZ) plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF) enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV‐BDNF infection was verified in primary neuronal culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats at 14 days prior to right middle cerebral artery occlusion (MCAo). SVZ tissues were collected from the brain and placed in Metrigel cultures 1 day after MCAo. Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local administration of AAV-BDNF significantly enhanced recovery of locomotor function and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ increases behavioral recovery post stroke, possibly through the enhancement of migration of cells from SVZ in stroke animals. Regional manipulation of BDNF expression through AAV may be a novel approach for neurorepair in stroke brains. PMID:24312581

  19. Effects of IFNγ administration on allograft rejection in ginbuna crucian carp.

    PubMed

    Shibasaki, Yasuhiro; Hatanaka, Chihiro; Matsuura, Yuta; Miyazawa, Ryuichiro; Yabu, Takeshi; Moritomo, Tadaaki; Nakanishi, Teruyuki

    2016-09-01

    In vertebrates, the rejection of allografts is primarily accomplished by cell-mediated immunity. We recently identified four IFNγ isoforms with antiviral activity in ginbuna crucian carp, Carassius auratus langsdorfii. However, involvement of the IFNγ isoforms in cell-mediated immunity, especially in T cell function remains unknown. Here we investigate expression of the IFNγ isoforms and effects of administration of recombinant IFNγ (rgIFNγ) isoforms in ginbuna scale allograft rejection. All four IFNγ isoforms showed significantly higher expression with the progression of graft rejection. Administration of rgIFNγrel 1 but not rgIFNγrel 2, rgIFNγ1 nor rgIFNγ2 enhanced allograft rejection. The number of CD4(+) and CD8α(+) cells increased in early stages of rejection, while sIgM(+) cells were higher than controls at day 0 and 5 in the rgIFNγrel 1 administrated group. Expression of IFNγ1 and IFNγ2 mRNA was significantly up-regulated by rgIFNγrel 1 administration, while that of IFNγrel 1 and IFNγrel 2 was not. These results suggest different contributions of the four IFNγ isoforms toward the immune responses comprising allograft rejection. PMID:27156851

  20. [Clinical significance of calcium sensitizer].

    PubMed

    Sakata, Yasushi

    2013-04-01

    Oral inotropes did not always improve mortality of the patients with heart failure partly because of possible direct toxic effects of these agents on myocytes, exacerbating arrhythmias, enhancing neurohormonal activity. Ca(2 +) sensitizers such as pimobendan and levosimendan was expected to improve even mortality of the patients with heart failure through increasing cardiac contractility without a rise in intracellular calcium. However, the trials using these agents disappoint our expectations. We need the development of the agents which has more specific effect of Ca(2 +) sensitizing and the selection of the patients who will receive the benefits of Ca(2 +) sensitizers. PMID:23545748

  1. Operations Research and Higher Education Administration.

    ERIC Educational Resources Information Center

    Cheng, T. C . E.

    1993-01-01

    Illustrates the uses of operations research (OR) in higher education administration by reviewing the higher education system's most significant operational problems: resource allocation, financial planning, budgeting, formation of student project groups, scheduling and classroom allocation, student registration, tuition and fee structure…

  2. The Wage Gap and Administrative Salaries Today.

    ERIC Educational Resources Information Center

    Beyer, Kirk D.

    1992-01-01

    Analysis of national data on college administrator salaries by gender, minority/nonminority status, years of service, and institution type found that wage gaps related to gender and minority status persisted in 1991-92 but that interaction of length of service with other study variables explained a significant amount of this gap. (MSE)

  3. 76 FR 72328 - Miscellaneous Administrative Changes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ... amends the NASA FAR Supplement (NFS) to make miscellaneous non-substantive administrative changes to be... NASA. DATES: This direct final rule is effective January 23, 2012 unless Agency receives significant..., NASA will publish a timely withdrawal of the rule in the Federal Register. If no adverse comments...

  4. The Challenge of Creating Ethical Administrators.

    ERIC Educational Resources Information Center

    Edmonson, Stacey; Fisher, Alice

    2002-01-01

    Discusses the importance of administrator ethics in the quality of students' education. Points out that research shows a significant shortcoming in ethical awareness among educational leadership students. Argues that the study of ethics should be an essential component of any educational leadership preparation program. (Contains 13 references.)…

  5. Boiling significantly promotes photodegradation of perfluorooctane sulfonate.

    PubMed

    Lyu, Xian-Jin; Li, Wen-Wei; Lam, Paul K S; Yu, Han-Qing

    2015-11-01

    The application of photochemical processes for perfluorooctane sulfonate (PFOS) degradation has been limited by a low treatment efficiency. This study reports a significant acceleration of PFOS photodegradation under boiling condition compared with the non-boiling control. The PFOS decomposition rate increased with the increasing boiling intensity, but declined at a higher hydronium level or under oxygenation. These results suggest that the boiling state of solution resulted in higher effective concentrations of reactants at the gas-liquid interface and enhanced the interfacial mass transfer, thereby accelerating the PFOS decomposition. This study broadens our knowledge of PFOS photodegradation process and may have implications for development of efficient photodegradation technologies. PMID:26117498

  6. Administrative Aspects of Human Experimentation.

    ERIC Educational Resources Information Center

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  7. Administrative Law and Organization Theory

    ERIC Educational Resources Information Center

    Evan, William M.

    1977-01-01

    Considered are some trends in American administrative law, some trends in organization theory, a model of the administrative process, and several potentially useful research strategies. The analysis has implications for comparative research on legal systems. (Author/LBH)

  8. Administration for Children and Families

    MedlinePlus

    ... Office ACF Help Center (help-center) Administration for Native Americans (ANA) Administration on Children, Youth and Families (ACYF) ... Global Populations Hispanic Outreach Homelessness Human Trafficking LGBT Native Americans/Tribes Unaccompanied Children Grants & Funding Expand How to ...

  9. Selecting the Administrative Computing Executive.

    ERIC Educational Resources Information Center

    Bielec, John A.

    1985-01-01

    Important steps in the computing administrator selection process are outlined, including: reviewing the administrative computing organization, determining a search methodology, selecting a search or screening committee, narrowing the candidate pool, scheduling interviews and evaluating candidates, and conducting negotiations. (MSE)

  10. Administrative Implications of Curriculum Reform

    ERIC Educational Resources Information Center

    Abbott, Max G.; Eidell, Terry L.

    1970-01-01

    The director of the Center for the Advanced Study of Educational Administration at the University of Oregon and one of his associates discuss the new role of administration in an individual-oriented educational system. (AA)

  11. Neurochemical Effects of Chronic Administration of Calcitriol in Rats

    PubMed Central

    Jiang, Pei; Zhang, Li-Hong; Cai, Hua-Lin; Li, Huan-De; Liu, Yi-Ping; Tang, Mi-Mi; Dang, Rui-Li; Zhu, Wen-Ye; Xue, Ying; He, Xin

    2014-01-01

    Despite accumulating data showing the various neurological actions of vitamin D (VD), its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D) administration (50 ng/kg/day or 100 ng/kg/day). Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA) status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD) 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS) expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA) expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function. PMID:25533012

  12. SIGNIFICANT NATURAL HERITAGE AREAS (NC)

    EPA Science Inventory

    The North Carolina Department of Environment and Natural Resources, Division of Parks and Recreation, Natural Heritage Program in cooperation with the NC Center for Geographic Information & Analysis, developed the Significant Natural Heritage Areas digital data to determine the a...

  13. Significant Scales in Community Structure

    PubMed Central

    Traag, V. A.; Krings, G.; Van Dooren, P.

    2013-01-01

    Many complex networks show signs of modular structure, uncovered by community detection. Although many methods succeed in revealing various partitions, it remains difficult to detect at what scale some partition is significant. This problem shows foremost in multi-resolution methods. We here introduce an efficient method for scanning for resolutions in one such method. Additionally, we introduce the notion of “significance” of a partition, based on subgraph probabilities. Significance is independent of the exact method used, so could also be applied in other methods, and can be interpreted as the gain in encoding a graph by making use of a partition. Using significance, we can determine “good” resolution parameters, which we demonstrate on benchmark networks. Moreover, optimizing significance itself also shows excellent performance. We demonstrate our method on voting data from the European Parliament. Our analysis suggests the European Parliament has become increasingly ideologically divided and that nationality plays no role. PMID:24121597

  14. Significant Decisions in Labor Cases.

    ERIC Educational Resources Information Center

    Monthly Labor Review, 1979

    1979-01-01

    Several significant court decisions involving labor cases are discussed including a series of decisions concerning constitutional protections afforded aliens; the First Amendment and national labor relations laws; and the bifurcated backpay rule. (BM)

  15. Astronomical Significance of Ancient Monuments

    NASA Astrophysics Data System (ADS)

    Simonia, I.

    2011-06-01

    Astronomical significance of Gokhnari megalithic monument (eastern Georgia) is considered. Possible connection of Amirani ancient legend with Gokhnari monument is discussed. Concepts of starry practicality and solar stations are proposed.

  16. Three Generations of Educational Administration.

    ERIC Educational Resources Information Center

    Sharpe, F. G.

    This paper compares two Australian educational administration texts published in 1963 to reflect critically on the radical changes that have occurred in educational administration in Australia since then. The books are "Headmasters for Better Schools," by Bassett, Crane, and Walker; and "Training the Administrator," by Cunningham and Radford. The…

  17. Special Education Administration Training Program.

    ERIC Educational Resources Information Center

    Watherman, Richard F.; Hollingsworth, Sue Ann

    Presented are course materials from a competency based education program in special education administration. It is explained that the Special Education Administration Training Program (SEATP) is designed for continuing education of administrators. Materials are divided into three self contained curriculum areas: fiscal management, personnel…

  18. The Future of Public Administration.

    ERIC Educational Resources Information Center

    Cleveland, Harlan

    Past approaches to public administration, the diminishing distinctions between foreign and domestic policy, the role of the public administrator, and leadership qualities are discussed. As a relatively young discipline, public administration first focused on scientific management (1920's). It then shifted to the art and science of getting things…

  19. Administrative Uses of the Microcomputer.

    ERIC Educational Resources Information Center

    Spuck, Dennis W.; Atkinson, Gene

    1983-01-01

    An outline of microcomputer applications for administrative computing in education is followed by discussions of aspects of office automation, database management systems, management information systems, administrative computer systems, and software. Several potential problems relating to administrative computing in education are identified.…

  20. Certification of Financial Aid Administrators

    ERIC Educational Resources Information Center

    Peterson, Stacey A.

    2011-01-01

    The certification of financial aid administrators has been debated for over 37 years. A job satisfaction survey conducted by the National Association of Student Financial Aid Administrators (NASFAA, 2008a) revealed that college and university administrators' perceptions of the efficiency, effectiveness, and quality of the services provided by the…