Increased sensitivity to angiotensin II is present postpartum in women with a history of hypertensive pregnancy.

PubMed

Saxena, Aditi R; Karumanchi, S Ananth; Brown, Nancy J; Royle, Caroline M; McElrath, Thomas F; Seely, Ellen W

2010-05-01

Pregnancies complicated by new-onset hypertension are associated with increased sensitivity to angiotensin II, but it is unclear whether this sensitivity persists postpartum. We studied pressor response to infused angiotensin II in 25 normotensive postpartum women in both high- and low-sodium balance. Ten women had a history of hypertensive pregnancy (5 with preeclampsia; 5 with transient hypertension of pregnancy), and 15 women had a history of uncomplicated, normotensive pregnancy. Systolic and diastolic blood pressures, aldosterone, and soluble fms-like tyrosine kinase 1 levels were measured before and after angiotensin II infusion in both dietary phases. In high sodium balance, women with a history of hypertensive pregnancy were normotensive but had significantly higher systolic and diastolic blood pressures than controls (115 versus 104 mm Hg and 73 versus 65 mm Hg, respectively; P<0.05). Women with a history of hypertensive pregnancy had a pressor response to salt loading, demonstrated by an increase in systolic blood pressure on a high-salt diet. They also had greater systolic pressor response (10 versus 2 mm Hg; P=0.03), greater increase in aldosterone (56.8 versus 30.8 ng/dL; P=0.03), and increase in soluble fms-like tyrosine kinase 1 levels (11.0 versus -18.9 pg/mL; P=0.02) after infusion of angiotensin II in low-sodium balance compared with controls. Thus, women with a history of hypertensive pregnancy demonstrated salt sensitivity of blood pressure and had increased pressor, adrenal, and soluble fms-like tyrosine kinase 1 responses to infused angiotensin II in low-sodium balance. Increased sensitivity to angiotensin II observed during pregnancy in women with hypertensive pregnancy is present postpartum; this feature may contribute to future cardiovascular risk in these women.

Highly sensitive wearable strain sensor based on silver nanowires and nanoparticles.

PubMed

Shengbo, Sang; Lihua, Liu; Aoqun, Jian; Qianqian, Duan; Jianlong, Ji; Qiang, Zhang; Wendong, Zhang

2018-06-22

Here, we propose a highly sensitive and stretchable strain sensor based on silver nanoparticles and nanowires (Ag NPs and NWs), advancing the rapid development of electronic skin. To improve the sensitivity of strain sensors based on silver nanowires (Ag NWs), Ag NPs and NWs were added to polydimethylsiloxane (PDMS) as an aid filler. Silver nanoparticles (Ag NPs) increase the conductive paths for electrons, leading to the low resistance of the resulting sensor (14.9 Ω). The strain sensor based on Ag NPs and NWs showed strong piezoresistivity with a tunable gauge factor (GF) at 3766, and a change in resistance as the strain linearly increased from 0% to 28.1%. The high GF demonstrates the irreplaceable role of Ag NPs in the sensor. Moreover, the applicability of our high-performance strain sensor has been demonstrated by its ability to sense movements caused by human talking, finger bending, wrist raising and walking.

Demonstration of SiC Pressure Sensors at 750 C

NASA Technical Reports Server (NTRS)

Okojie, Robert S.; Lukco, Dorothy; Nguyen, Vu; Savrun, Ender

2014-01-01

We report the first demonstration of MEMS-based 4H-SiC piezoresistive pressure sensors tested at 750 C and in the process confirmed the existence of strain sensitivity recovery with increasing temperature above 400 C, eventually achieving near or up to 100% of the room temperature values at 750 C. This strain sensitivity recovery phenomenon in 4H-SiC is uncharacteristic of the well-known monotonic decrease in strain sensitivity with increasing temperature in silicon piezoresistors. For the three sensors tested, the room temperature full-scale output (FSO) at 200 psig ranged between 29 and 36 mV. Although the FSO at 400 C dropped by about 60%, full recovery was achieved at 750 C. This result will allow the operation of SiC pressure sensors at higher temperatures, thereby permitting deeper insertion into the engine combustion chamber to improve the accurate quantification of combustor dynamics.

Highly sensitive wearable strain sensor based on silver nanowires and nanoparticles

NASA Astrophysics Data System (ADS)

Shengbo, Sang; Lihua, Liu; Aoqun, Jian; Qianqian, Duan; Jianlong, Ji; Qiang, Zhang; Wendong, Zhang

2018-06-01

Here, we propose a highly sensitive and stretchable strain sensor based on silver nanoparticles and nanowires (Ag NPs and NWs), advancing the rapid development of electronic skin. To improve the sensitivity of strain sensors based on silver nanowires (Ag NWs), Ag NPs and NWs were added to polydimethylsiloxane (PDMS) as an aid filler. Silver nanoparticles (Ag NPs) increase the conductive paths for electrons, leading to the low resistance of the resulting sensor (14.9 Ω). The strain sensor based on Ag NPs and NWs showed strong piezoresistivity with a tunable gauge factor (GF) at 3766, and a change in resistance as the strain linearly increased from 0% to 28.1%. The high GF demonstrates the irreplaceable role of Ag NPs in the sensor. Moreover, the applicability of our high-performance strain sensor has been demonstrated by its ability to sense movements caused by human talking, finger bending, wrist raising and walking.

Demonstration of sensitivity increase in mercury free-spin-precession magnetometers due to laser-based readout for neutron electric dipole moment searches

NASA Astrophysics Data System (ADS)

Ban, G.; Bison, G.; Bodek, K.; Daum, M.; Fertl, M.; Franke, B.; Grujić, Z. D.; Heil, W.; Horras, M.; Kasprzak, M.; Kermaidic, Y.; Kirch, K.; Koch, H.-C.; Komposch, S.; Kozela, A.; Krempel, J.; Lauss, B.; Lefort, T.; Mtchedlishvili, A.; Pignol, G.; Piegsa, F. M.; Prashanth, P.; Quéméner, G.; Rawlik, M.; Rebreyend, D.; Ries, D.; Roccia, S.; Rozpedzik, D.; Schmidt-Wellenburg, P.; Severijns, N.; Weis, A.; Wyszynski, G.; Zejma, J.; Zsigmond, G.

2018-07-01

We report on a laser based 199Hg co-magnetometer deployed in an experiment searching for a permanent electric dipole moment of the neutron. We demonstrate a more than five times increased signal to-noise-ratio in a direct comparison measurement with its 204Hg discharge bulb-based predecessor. An improved data model for the extraction of important system parameters such as the degrees of absorption and polarization is derived. Laser- and lamp-based data-sets can be consistently described by the improved model which permits to compare measurements using the two different light sources and to explain the increase in magnetometer performance. The laser-based magnetometer satisfies the magnetic field sensitivity requirements for the next generation nEDM experiments.

Airway extravasation induced by increasing airway temperature in ovalbumin-sensitized rats

PubMed Central

Hsu, Chun-Chun; Tapia, Reyno J.; Lee, Lu-Yuan

2015-01-01

This study was carried out to determine whether hyperventilation of humidified warm air (HWA) induced airway extravasation in ovalbumin (Ova)-sensitized rats. Our results showed: 1) After isocapnic hyperventilation with HWA for 2 min, tracheal temperature (Ttr) was increased to 40.3°C, and the Evans blue contents in major airways and lung tissue were elevated to 651% and 707%, respectively, of that after hyperventilation with humidified room air in Ova-sensitized rats; this striking effect of HWA was absent in control rats. 2) The HWA-induced increase in Evans blue content in sensitized rats was completely prevented by a pretreatment with either L-732138, a selective antagonist of neurokinin type 1 (NK-1) receptor, or formoterol, a selective agonist of β2 adrenoceptor. This study demonstrated that an increase in airway temperature induced protein extravasation in the major airways and lung tissue of sensitized rats, and an activation of the NK-1 receptor by tachykinins released from bronchopulmonary C-fiber nerve endings was primarily responsible. PMID:25864799

Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia.

PubMed

Willen, Shaina M; Rodeghier, Mark; Strunk, Robert C; Bacharier, Leonard B; Rosen, Carol L; Kirkham, Fenella J; DeBaun, Michael R; Cohen, Robyn T

2018-02-01

Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso-occlusive pain episodes among children with sickle cell anaemia (SCA). Aeroallergen sensitization is a risk factor for asthma. We hypothesized that aeroallergen sensitization is associated with an increased incidence of hospitalizations for ACS and pain. Participants in a multicentre, longitudinal cohort study, aged 4-18 years with SCA, underwent skin prick testing to ten aeroallergens. ACS and pain episodes were collected from birth until the end of the follow-up period. The number of positive skin tests were tested for associations with prospective rates of ACS and pain. Multivariable models demonstrated additive effects of having positive skin tests on future rates of ACS (incidence rate ratio (IRR) for each positive test 1·23, 95% confidence interval [CI] 1·11-1·36, P < 0·001). Aeroallergen sensitization was not associated with future pain (IRR 1·14, 95%CI 0·97-1·33, P = 0·11). Our study demonstrated that children with SCA and aeroallergen sensitization are at increased risk for future ACS. Future research is needed to determine whether identification of specific sensitizations and allergen avoidance and treatment reduce the risk of ACS for children with SCA. © 2018 John Wiley & Sons Ltd.

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite-induced asthma in murine offspring.

PubMed

Richgels, Phoebe K; Yamani, Amnah; Chougnet, Claire A; Lewkowich, Ian P

2017-11-01

Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. We sought to determine whether maternal HDM exposure influences asthma development in offspring. Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, T H 2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, T H 2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Influence of polyunsaturated fatty acid supplementation and membrane fluidity on ozone and nitrogen dioxide sensitivity of rat alveolar macrophages

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

Rietjens, I.M.; van Tilburg, C.A.; Coenen, T.M.

1987-01-01

The phospholipid polyunsaturated fatty acid (PUFA) content and the membrane fluidity of rat alveolar macrophages were modified dose-dependently and in different ways. This was done to study the importance of both membrane characteristics for the cellular sensitivity toward ozone and nitrogen dioxide. Cells preincubated with arachidonic acid (20:4) complexed to bovine serum albumin (BSA) demonstrated an increased in vitro sensitivity versus ozone and nitrogen dioxide. The phenomenon was only observed at the highest 20:4 concentrations tested, whereas the membrane fluidity of the 20:4-treated cells already showed a maximum increase at lower preincubation concentrations. Hence it could be concluded that themore » increased ozone and nitrogen dioxide sensitivity of PUFA-enriched cells is not caused by their increased membrane fluidity, resulting in an increased accessibility of sensitive cellular fatty acid moieties or amino acid residues. This conclusion receives further support from other observations. These results strongly support the involvement of lipid oxidation in the mechanism(s) of toxic action of both ozone and nitrogen dioxide in an intact cell system.« less

Anxiety Sensitivity and Panic Attacks: A 1-Year Longitudinal Study

ERIC Educational Resources Information Center

Li, Wen; Zinbarg, Richard E.

2007-01-01

The hypothesis that anxiety sensitivity (AS) is a risk factor for panic genesis has obtained compelling support, but the clinical/practical importance of AS in panic genesis has been questioned. In addition, the association between panic experience and AS increase has not been clearly demonstrated. Through this 1-year longitudinal study among…

Epac activation sensitizes rat sensory neurons through activation of Ras.

PubMed

Shariati, Behzad; Thompson, Eric L; Nicol, Grant D; Vasko, Michael R

2016-01-01

Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2'-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. Copyright © 2015 Elsevier Inc. All rights reserved.

Epac activation sensitizes rat sensory neurons via activation of Ras

PubMed Central

Shariati, Behzad; Thompson, Eric L.; Nicol, Grant D.; Vasko, Michael R.

2015-01-01

Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2′-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. PMID:26596174

Enhancement in sensitivity of graphene-based zinc oxide assisted bimetallic surface plasmon resonance (SPR) biosensor

NASA Astrophysics Data System (ADS)

Kumar, Rajeev; Kushwaha, Angad S.; Srivastava, Monika; Mishra, H.; Srivastava, S. K.

2018-03-01

In the present communication, a highly sensitive surface plasmon resonance (SPR) biosensor with Kretschmann configuration having alternate layers, prism/zinc oxide/silver/gold/graphene/biomolecules (ss-DNA) is presented. The optimization of the proposed configuration has been accomplished by keeping the constant thickness of zinc oxide (32 nm), silver (32 nm), graphene (0.34 nm) layer and biomolecules (100 nm) for different values of gold layer thickness (1, 3 and 5 nm). The sensitivity of the proposed SPR biosensor has been demonstrated for a number of design parameters such as gold layer thickness, number of graphene layer, refractive index of biomolecules and the thickness of biomolecules layer. SPR biosensor with optimized geometry has greater sensitivity (66 deg/RIU) than the conventional (52 deg/RIU) as well as other graphene-based (53.2 deg/RIU) SPR biosensor. The effect of zinc oxide layer thickness on the sensitivity of SPR biosensor has also been analysed. From the analysis, it is found that the sensitivity increases significantly by increasing the thickness of zinc oxide layer. It means zinc oxide intermediate layer plays an important role to improve the sensitivity of the biosensor. The sensitivity of SPR biosensor also increases by increasing the number of graphene layer (upto nine layer).

The sensitivity of Bacillus subtilis to diverse antimicrobial compounds is influenced by Abh.

PubMed

Murray, Ewan J; Stanley-Wall, Nicola R

2010-12-01

Abh is a transition state regulator of Bacillus subtilis that controls biofilm formation and the production of several diverse antimicrobial compounds. Using a high-throughput non-biased technique, we show for the first time that Abh influences the sensitivity of B. subtilis to diverse antimicrobial compounds. Following up on these findings with a combination of classical genetics and antibiotic susceptibility assays, we demonstrate that Abh influences cellular processes such as the remodelling of the cell wall. We present data demonstrating that the extracytoplasmic function sigma factor σ(X) controls resistance to β-lactam antibiotics by activating abh transcription. Downstream from Abh, activation of slrR expression by Abh is responsible for controlling the sensitivity of B. subtilis to such antibiotics due to the role that SlrR plays in regulating autolysin biosynthesis. The abh mutant additionally exhibits increased resistance to aminoglycoside antimicrobials. We confirm that aminoglycoside killing of B. subtilis is likely to be caused by oxidative damage but rule out the possibility that the increased resistance of the abh mutant to aminoglycosides is due to a general increase in resistance to oxidative stress.

Sensitivity Changes over the Course of Infection Increases the Likelihood of Resistance Against Fusion but Not CCR5 Receptor Blockers

PubMed Central

Chatziandreou, Nikolaos; Arauz, Ana Belen; Freitas, Ines; Nyein, Phyu Hninn; Fenton, Gregory; Mehta, Shruti H.; Kirk, Gregory D.

2012-01-01

Abstract As HIV-1 evolves over the course of infection, resistance against antiretrovirals may arise in the absence of drug pressure, especially against receptor and fusion blockers because of the extensive changes observed in the envelope glycoprotein. Here we show that viruses from the chronic phase of disease are significantly less sensitive to CCR5 receptor and fusion blockers compared to early infection variants. Differences in susceptibility to CCR5 antagonists were observed in spite of no demonstrable CXCR4 receptor utilization. No significant sensitivity differences were observed to another entry blocker, soluble CD4, or to reverse transcriptase, protease, or integrase inhibitors. Chronic as compared to early phase variants demonstrated greater replication when passaged in the presence of subinhibitory concentrations of fusion but not CCR5 receptor inhibitors. Fusion antagonist resistance, however, emerged from only one chronic phase virus culture. Because sensitivity to receptor and fusion antagonists is correlated with receptor affinity and fusion capacity, respectively, changes that occur in the envelope glycoprotein over the course of infection confer greater ability to use the CCR5 receptor and increased fusion ability. Our in vitro passage studies suggest that these evolving phenotypes increase the likelihood of resistance against fusion but not CCR5 receptor blockers. PMID:22650962

Enhancing the sensitivity of slow light MZI biosensors through multi-hole defects

NASA Astrophysics Data System (ADS)

Qin, Kun; Zhao, Yiliang; Hu, Shuren; Weiss, Sharon M.

2018-02-01

We demonstrate enhanced detection sensitivity of a slow light Mach-Zehnder interferometer (MZI) sensor by incorporating multi-hole defects (MHDs). Slow light MZI biosensors with a one-dimensional photonic crystal in one arm have been previously shown to improve the performance of traditional MZI sensors based on the increased lightmatter interaction that takes place in the photonic crystal region of the structure. Introducing MHDs in the photonic crystal region increases the available surface area for molecular attachment and further increases the enhanced lightmatter interaction capability of slow light MZIs. The MHDs allow analyte to interact with a greater fraction of the guided wave in the MZI. For a slow light MHD MZI sensor with a 16 μm long sensing arm, a bulk sensitivity of 151,000 rad/RIU-cm is demonstrated experimentally, which is approximately two-fold higher than our previously reported slow light MZI sensors and thirteen-fold higher than traditional MZI biosensors with millimeter length sensing regions. For the label-free detection of nucleic acids, the slow light MZI with MHDs also exhibits a two-fold sensitivity improvement in experiment compared to the slow light MZI without MHDs. Because the detection sensitivity of slow light MHD MZIs scales with the length of the sensing arm, the tradeoff between detection limit and device size can be appropriately mitigated for different applications. All experimental results presented in this work are in good agreement with finite difference-time domain-calculations. Overall, the slow light MZI biosensors with MHDs are a promising platform for highly sensitive and multiplexed lab-on-chip systems.

Real-time polarization-sensitive optical coherence tomography data processing with parallel computing

PubMed Central

Liu, Gangjun; Zhang, Jun; Yu, Lingfeng; Xie, Tuqiang; Chen, Zhongping

2010-01-01

With the increase of the A-line speed of optical coherence tomography (OCT) systems, real-time processing of acquired data has become a bottleneck. The shared-memory parallel computing technique is used to process OCT data in real time. The real-time processing power of a quad-core personal computer (PC) is analyzed. It is shown that the quad-core PC could provide real-time OCT data processing ability of more than 80K A-lines per second. A real-time, fiber-based, swept source polarization-sensitive OCT system with 20K A-line speed is demonstrated with this technique. The real-time 2D and 3D polarization-sensitive imaging of chicken muscle and pig tendon is also demonstrated. PMID:19904337

Video-feedback intervention increases sensitive parenting in ethnic minority mothers: a randomized control trial.

PubMed

Yagmur, Sengul; Mesman, Judi; Malda, Maike; Bakermans-Kranenburg, Marian J; Ekmekci, Hatice

2014-01-01

Using a randomized control trial design we tested the effectiveness of a culturally sensitive adaptation of the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) in a sample of 76 Turkish minority families in the Netherlands. The VIPP-SD was adapted based on a pilot with feedback of the target mothers, resulting in the VIPP-TM (VIPP-Turkish Minorities). The sample included families with 20-47-month-old children with high levels of externalizing problems. Maternal sensitivity, nonintrusiveness, and discipline strategies were observed during pretest and posttest home visits. The VIPP-TM was effective in increasing maternal sensitivity and nonintrusiveness, but not in enhancing discipline strategies. Applying newly learned sensitivity skills in discipline situations may take more time, especially in a cultural context that favors more authoritarian strategies. We conclude that the VIPP-SD program and its video-feedback approach can be successfully applied in immigrant families with a non-Western cultural background, with demonstrated effects on parenting sensitivity and nonintrusiveness.

Binary pressure-sensitive paint measurements using miniaturised, colour, machine vision cameras

NASA Astrophysics Data System (ADS)

Quinn, Mark Kenneth

2018-05-01

Recent advances in machine vision technology and capability have led to machine vision cameras becoming applicable for scientific imaging. This study aims to demonstrate the applicability of machine vision colour cameras for the measurement of dual-component pressure-sensitive paint (PSP). The presence of a second luminophore component in the PSP mixture significantly reduces its inherent temperature sensitivity, increasing its applicability at low speeds. All of the devices tested are smaller than the cooled CCD cameras traditionally used and most are of significantly lower cost, thereby increasing the accessibility of such technology and techniques. Comparisons between three machine vision cameras, a three CCD camera, and a commercially available specialist PSP camera are made on a range of parameters, and a detailed PSP calibration is conducted in a static calibration chamber. The findings demonstrate that colour machine vision cameras can be used for quantitative, dual-component, pressure measurements. These results give rise to the possibility of performing on-board dual-component PSP measurements in wind tunnels or on real flight/road vehicles.

Transparent, Flexible, Conformal Capacitive Pressure Sensors with Nanoparticles.

PubMed

Kim, Hyeohn; Kim, Gwangmook; Kim, Taehoon; Lee, Sangwoo; Kang, Donyoung; Hwang, Min-Soo; Chae, Youngcheol; Kang, Shinill; Lee, Hyungsuk; Park, Hong-Gyu; Shim, Wooyoung

2018-02-01

The fundamental challenge in designing transparent pressure sensors is the ideal combination of high optical transparency and high pressure sensitivity. Satisfying these competing demands is commonly achieved by a compromise between the transparency and usage of a patterned dielectric surface, which increases pressure sensitivity, but decreases transparency. Herein, a design strategy for fabricating high-transparency and high-sensitivity capacitive pressure sensors is proposed, which relies on the multiple states of nanoparticle dispersity resulting in enhanced surface roughness and light transmittance. We utilize two nanoparticle dispersion states on a surface: (i) homogeneous dispersion, where each nanoparticle (≈500 nm) with a size comparable to the visible light wavelength has low light scattering; and (ii) heterogeneous dispersion, where aggregated nanoparticles form a micrometer-sized feature, increasing pressure sensitivity. This approach is experimentally verified using a nanoparticle-dispersed polymer composite, which has high pressure sensitivity (1.0 kPa -1 ), and demonstrates excellent transparency (>95%). We demonstrate that the integration of nanoparticle-dispersed capacitor elements into an array readily yields a real-time pressure monitoring application and a fully functional touch device capable of acting as a pressure sensor-based input device, thereby opening up new avenues to establish processing techniques that are effective on the nanoscale yet applicable to macroscopic processing. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance.

PubMed

Palanivel, R; Fullerton, M D; Galic, S; Honeyman, J; Hewitt, K A; Jorgensen, S B; Steinberg, G R

2012-11-01

Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known. We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed. The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic-euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1). These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity.

Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes.

PubMed

Taylor, I Mitch; Robbins, Elaine M; Catt, Kasey A; Cody, Patrick A; Happe, Cassandra L; Cui, Xinyan Tracy

2017-03-15

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced Dopamine Detection Sensitivity by PEDOT/Graphene Oxide Coating on in vivo Carbon Fiber Electrodes

PubMed Central

Taylor, I. Mitch; Robbins, Elaine M.; Catt, Kasey A.; Cody, Patrick A.; Weaver, Cassandra L.; Cui, Xinyan Tracy

2016-01-01

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA’s oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. PMID:27268013

Arginine vasopressin antagonizes the effects of prostaglandin E2 on the spontaneous activity of warm-sensitive and temperature-insensitive neurons in the medial preoptic area in rats.

PubMed

Xu, Jian-Hui; Hou, Xiao-Yu; Tang, Yu; Luo, Rong; Zhang, Jie; Liu, Chang; Yang, Yong-Lu

2018-01-01

Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E 2 (PGE 2 ) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE 2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE 2 on warm-sensitive neurons, and reversed the excitatory effect of PGE 2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE 2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V 1a receptor antagonist, suggesting that V 1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE 2 -induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE 2 -induced increase in that in low-slope temperature-insensitive neurons through the V 1a receptor. Together, these data indicated that AVP antagonized the PGE 2 -induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE 2 -induced change in the prepotential of these neurons in a V 1a receptor-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

[Different responses of DD/He and CC57BR/Mv mice to fasting].

PubMed

Baginskaia, N V; Vasil'eva, E D; Il'nitskaia, S I; Kaledin, V I

2004-03-01

Reaction to fasting of 2 mice strains differing in their sensitivity to spontaneous and induced hepatocarcinogenesis, has been investigated. It was shown that mice of both strains displayed similar stress reaction after 3-day fasting manifested in increase in blood corticosterone level; and decrease in testosterone level. At the same time, both strains demonstrated opposite changes at tissue- and enzyme levels in the liver. It was shown that DD/He mice, highly sensitive to induction of liver tumors, were characterized by significant increase in tyrosine aminotransferase (TAT) activity and reduction of lipid droplets in hepatocytes. CC57BR/Mv mice, demonstrating high frequency of spontaneous hepatomas and insensitive to induction of such tumors, were characterized by a decrease in the TAT activity and fatty infiltration of the liver.

Neural-Net Based Optical NDE Method for Structural Health Monitoring

NASA Technical Reports Server (NTRS)

Decker, Arthur J.; Weiland, Kenneth E.

2003-01-01

This paper answers some performance and calibration questions about a non-destructive-evaluation (NDE) procedure that uses artificial neural networks to detect structural damage or other changes from sub-sampled characteristic patterns. The method shows increasing sensitivity as the number of sub-samples increases from 108 to 6912. The sensitivity of this robust NDE method is not affected by noisy excitations of the first vibration mode. A calibration procedure is proposed and demonstrated where the output of a trained net can be correlated with the outputs of the point sensors used for vibration testing. The calibration procedure is based on controlled changes of fastener torques. A heterodyne interferometer is used as a displacement sensor for a demonstration of the challenges to be handled in using standard point sensors for calibration.

Sensitivities of ionic explosives

NASA Astrophysics Data System (ADS)

Politzer, Peter; Lane, Pat; Murray, Jane S.

2017-03-01

We have investigated the relevance for ionic explosive sensitivity of three factors that have been demonstrated to be related to the sensitivities of molecular explosives. These are (1) the maximum available heat of detonation, (2) the amount of free space per molecule (or per formula unit) in the crystal lattice and (3) specific features of the electrostatic potential on the molecular or ionic surface. We find that for ionic explosives, just as for molecular ones, there is an overall tendency for impact sensitivity to increase as the maximum detonation heat release is greater. This means that the usual emphasis upon designing explosives with large heats of detonation needs to be tempered somewhat. We also show that a moderate detonation heat release does not preclude a high level of detonation performance for ionic explosives, as was already demonstrated for molecular ones. Relating the free space per formula unit to sensitivity may require a modified procedure for ionic explosives; this will continue to be investigated. Finally, an encouraging start has been made in linking impact sensitivities to the electrostatic potentials on ionic surfaces, although limited so far to ammonium salts.

The effects of mild and severe traumatic brain injury on speed of information processing as measured by the computerized tests of information processing (CTIP).

PubMed

Tombaugh, Tom N; Rees, Laura; Stormer, Peter; Harrison, Allyson G; Smith, Andra

2007-01-01

In spite of the fact that reaction time (RT) measures are sensitive to the effects of traumatic brain injury (TBI), few RT procedures have been developed for use in standard clinical evaluations. The computerized test of information processing (CTIP) [Tombaugh, T. N., & Rees, L. (2000). Manual for the computerized tests of information processing (CTIP). Ottawa, Ont.: Carleton University] was designed to measure the degree to which TBI decreases the speed at which information is processed. The CTIP consists of three computerized programs that progressively increase the amount of information that is processed. Results of the current study demonstrated that RT increased as the difficulty of the CTIP tests increased (known as the complexity effect), and as severity of injury increased (from mild to severe TBI). The current study also demonstrated the importance of selecting a non-biased measure of variability. Overall, findings suggest that the CTIP is an easy to administer and sensitive measure of information processing speed.

Acid-Sensitive Sheddable PEGylated, Mannose-Modified Nanoparticles Increase the Delivery of Betamethasone to Chronic Inflammation Sites in a Mouse Model.

PubMed

O'Mary, Hannah L; Aldayel, Abdulaziz M; Valdes, Solange A; Naguib, Youssef W; Li, Xu; Salvady, Karun; Cui, Zhengrong

2017-06-05

Inflammation is implicated in a host of chronic illnesses. Within these inflamed tissues, the pH of the microenvironment is decreased and immune cells, particularly macrophages, infiltrate the area. Additionally, the vascular integrity of these sites is altered with increased fenestrations between endothelial cells. These distinctive properties may be exploited to enhance targeted delivery of anti-inflammatory therapies. Using a mouse model of chronic inflammation, we previously showed that acid-sensitive sheddable PEGylation increases the distribution and retention of nanoparticles in chronic inflammation sites. Here we demonstrated that surface modification of the acid-sensitive sheddable PEGylated nanoparticles with mannose, a ligand to mannose receptors present in chronic inflammation sites, significantly increases the targeted delivery of the nanoparticles to these areas. Furthermore, we showed that the acid-sensitive sheddable PEGylated, mannose-modified nanoparticles are able to significantly increase the delivery of betamethasone-21-acetate (BA), a model anti-inflammatory compound, to chronic inflammation sites as compared to free BA. These results highlight the ability to engineer formulations to target chronic inflammation sites by exploiting the microenvironment of these regions.

Quantum-Noise-Limited Sensitivity-Enhancement of a Passive Optical Cavity by a Fast-Light Medium

NASA Technical Reports Server (NTRS)

Smith, David D.; Luckay, H. A.; Chang, Hongrok; Myneni, Krishna

2016-01-01

We demonstrate for a passive optical cavity containing an intracavity dispersive atomic medium, the increase in scale factor near the critical anomalous dispersion is not cancelled by mode broadening or attenuation, resulting in an overall increase in the predicted quantum-noiselimited sensitivity. Enhancements of over two orders of magnitude are measured in the scale factor, which translates to greater than an order-of-magnitude enhancement in the predicted quantumnoise- limited measurement precision, by temperature tuning a low-pressure vapor of noninteracting atoms in a low-finesse cavity close to the critical anomalous dispersion condition. The predicted enhancement in sensitivity is confirmed through Monte-Carlo numerical simulations.

Quantum-Noise-Limited Sensitivity Enhancement of a Passive Optical Cavity by a Fast-Light Medium

NASA Technical Reports Server (NTRS)

Smith, David D.; Luckay, H. A.; Chang, Hongrok; Myneni, Krishna

2016-01-01

We demonstrate for a passive optical cavity containing a dispersive atomic medium, the increase in scale factor near the critical anomalous dispersion is not cancelled by mode broadening or attenuation, resulting in an overall increase in the predicted quantum-noise-limited sensitivity. Enhancements of over two orders of magnitude are measured in the scale factor, which translates to greater than an order-of-magnitude enhancement in the predicted quantum-noise-limited measurement precision, by temperature tuning a low-pressure vapor of non-interacting atoms in a low-finesse cavity close to the critical anomalous dispersion condition. The predicted enhancement in sensitivity is confirmed through Monte-Carlo numerical simulations.

MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by inhibiting mTOR signaling pathway and expression of MDR1.

PubMed

Li, Qiang; Xia, Xuefeng; Ji, Jie; Ma, Jianghui; Tao, Liang; Mo, Linjun; Chen, Wei

2017-05-16

Several studies have reported reduced miRNA-199a-3p (miR-199a-3p) in different human malignancies, however, little is known about miR-199a-3p in cholangiocarcinoma cells. In this study, we demonstrate the essential role and mechanism of miR-199a-3p in regulating cisplatin sensitivity in cholangiocarcinoma cell lines. Using a CCK-8 cell counting assay we found that expression of miR-199a-3p was positively correlated with cisplatin sensitivity in cholangiocarcinoma cell lines. MiR-199a-3p overexpression could decrease the proliferation rate and increase apoptosis of cholangiocarcinoma cells in the presence of cisplatin, while miR-199a-3p inhibition had the opposite effect. Further study demonstrated that mTOR was the target gene of miR-199a-3p, and that miR-199a-3p mimics could inhibit expression of mTOR, which consequently reduced the phosphorylation of its downstream proteins 4EBP1 and p70s6k. Rescue experiments proved that miR-199a-3p could increase the cisplatin sensitivity of cholangiocarcinoma cell lines by regulating mTOR expression. Moreover, we also found that miR-199a-3p overexpression could reduce cisplatin induced MDR1 expression by decreasing the synthesis and increasing the degradation of MDR1, thus enhancing the effectiveness of cisplatin in cholangiocarcinoma. In conclusion, miR-199a-3p could increase cisplatin sensitivity of cholangiocarcinoma cell lines by inhibiting the activity of the mTOR signaling pathway and decreasing the expression of MDR1.

On the Binding Stress-Enhanced Sensitivity of (Pb(Mg1/3Nb2/3)O3)0.65-(PbTiO3) 0.35 (PMN-PT) Piezoelectric Plate Sensor (PEPS)

NASA Astrophysics Data System (ADS)

Wu, Wei

(Pb(Mg1/3Nb2/3)O3)0.65-(PbTiO 3)0.35 (PMN-PT) piezoelectric plate sensor (PEPS) showed enhanced sensitivity in chemical and biological sensing applications which has been attributed to binding-induced crystalline orientation switching in the PMN-PT layer. However, so far there has been no direct demonstration of PEPS crystalline orientation switching upon target-analyte binding. Using biotin and streptavidin binding as a model detection system and by direct X-Ray diffraction observations after analyte binding we have unambiguously demonstrated that switching of the crystalline orientations of the PMN-PT layer indeed occurred. In addition, we have shown that PEPS sensitivity enhancement increased with an increasing transverse electromechanical coupling constant, -k31, of the PMN-PT layer--which is known to correlate with the crystalline orientation switching capability--by increasing the grain size of the PMN-PT layer or by applying a DC bias electric field. Finally, unprecedented high sensitivity of PEPS with high -k31, (i.e., -k31 > 0.3) were illustrated by the aM (10-18 M) sensitivity of in situ DNA hybridization detection without amplification and by the 100 fg/ml (10-13 g/ml) sensitivity of rapid, in situ protein detection in biological fluids such as troponin I detection in serum for early sign of myocardial infarction (heart attack), Her2 detection in serum for cancer treatment and monitoring, Tn antigen and anti-Tn antibody detection in serum for early cancer detection, and Toxins detection in stool for Clostridium difficile infection detection.

Applying geologic sensitivity analysis to environmental risk management: The financial implications

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

Rogers, D.T.

The financial risks associated with environmental contamination can be staggering and are often difficult to identify and accurately assess. Geologic sensitivity analysis is gaining recognition as a significant and useful tool that can empower the user with crucial information concerning environmental risk management and brownfield redevelopment. It is particularly useful when (1) evaluating the potential risks associated with redevelopment of historical industrial facilities (brownfields) and (2) planning for future development, especially in areas of rapid development because the number of potential contaminating sources often increases with an increase in economic development. An examination of the financial implications relating to geologicmore » sensitivity analysis in southeastern Michigan from numerous case studies indicate that the environmental cost of contamination may be 100 to 1,000 times greater at a geologically sensitive location compared to the least sensitive location. Geologic sensitivity analysis has demonstrated that near-surface geology may influence the environmental impact of a contaminated site to a greater extent than the amount and type of industrial development.« less

Beating the Standard Sensitivity-Bandwidth Limit of Cavity-Enhanced Interferometers with Internal Squeezed-Light Generation

NASA Astrophysics Data System (ADS)

Korobko, M.; Kleybolte, L.; Ast, S.; Miao, H.; Chen, Y.; Schnabel, R.

2017-04-01

The shot-noise limited peak sensitivity of cavity-enhanced interferometric measurement devices, such as gravitational-wave detectors, can be improved by increasing the cavity finesse, even when comparing fixed intracavity light powers. For a fixed light power inside the detector, this comes at the price of a proportional reduction in the detection bandwidth. High sensitivity over a large span of signal frequencies, however, is essential for astronomical observations. It is possible to overcome this standard sensitivity-bandwidth limit using nonclassical correlations in the light field. Here, we investigate the internal squeezing approach, where the parametric amplification process creates a nonclassical correlation directly inside the interferometer cavity. We theoretically analyze the limits of the approach and measure 36% increase in the sensitivity-bandwidth product compared to the classical case. To our knowledge, this is the first experimental demonstration of an improvement in the sensitivity-bandwidth product using internal squeezing, opening the way for a new class of optomechanical force sensing devices.

Improving the sensitivity and specificity of a bioanalytical assay for the measurement of certolizumab pegol.

PubMed

Smeraglia, John; Silva, John-Paul; Jones, Kieran

2017-08-01

In order to evaluate placental transfer of certolizumab pegol (CZP), a more sensitive and selective bioanalytical assay was required to accurately measure low CZP concentrations in infant and umbilical cord blood. Results & methodology: A new electrochemiluminescence immunoassay was developed to measure CZP levels in human plasma. Validation experiments demonstrated improved selectivity (no matrix interference observed) and a detection range of 0.032-5.0 μg/ml. Accuracy and precision met acceptance criteria (mean total error ≤20.8%). Dilution linearity and sample stability were acceptable and sufficient to support the method. The electrochemiluminescence immunoassay was validated for measuring low CZP concentrations in human plasma. The method demonstrated a more than tenfold increase in sensitivity compared with previous assays, and improved selectivity for intact CZP.

Aconitine "challenge" test reveals a single whole-body exposure to diesel exhaust increases cardiac arrhythmia risk in hypertensive rats

EPA Science Inventory

Epidemiological studies demonstrate a significant association between cardiac electrical dysfunction, arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electri...

A circadian clock regulates sensitivity to cadmium in Paramecium tetraurelia.

PubMed

Hinrichsen, Robert D; Tran, Joseph R

2010-08-01

The heavy metal cadmium is a dangerous environmental toxicant that can be lethal to humans and other organisms. This paper demonstrates that cadmium is lethal to the ciliated protozoan Paramecium tetraurelia and that a circadian clock modulates the sensitivity of the cells to cadmium. Various concentrations of cadmium were shown to increase the number of behavioral responses, decrease the swimming speed of cells, and generate large vacuole formation in cells prior to death. Cells were grown in either 12-h light/12-h dark or constant dark conditions exhibited a toxic response to 500 microM CdCl(2); the sensitivity of the response was found to vary with a 24-h periodicity. Cells were most sensitive to cadmium at circadian time 0 (CT0), while they were least sensitive in the early evening (CT12). This rhythm persisted even when the cells were grown in constant dark. The oscillation in cadmium sensitivity was shown to be temperature-compensated; cells grown at 18 degrees C and 28 degrees C had a similar 24-h oscillation. Finally, phase shifting experiments demonstrated a phase-dependent response to light. These data establish the criteria required for a circadian clock and demonstrate that P. tetraurelia possesses a circadian-influenced regulatory component of the cadmium toxic response. The Paramecium system is shown to be an excellent model system for the study of the effects of biological rhythms on heavy metal toxicity.

Icaritin opposes the development of social aversion after defeat stress via increases of GR mRNA and BDNF mRNA in mice.

PubMed

Wu, Xiao; Wu, Jinfeng; Xia, Shijin; Li, Bei; Dong, Jingcheng

2013-11-01

Icariin is a major constituent of flavonoids isolated from Herba Epimedii. Several previous studies have demonstrated the antidepressant-like effects of icariin. After oral administration of icariin, 19 metabolites of icariin were detected in rat plasma. Icaritin is one such of metabolite of icariin. In this study, a chronic social defeat protocol is used as a mouse model for depression, and the effects of icaritin administration on social avoidance are investigated. The data indicates that icaritin (5mg/kg and 10mg/kg) oral administration opposes the development of social aversion after defeat stress. In vitro corticosterone sensitivity assay demonstrated that icaritin partially restored social defeat-induced impairment of glucocorticoid sensitivity. The expressions of GR mRNA and BDNFmRNA in the hippocampus were increased after icaritin treatment. Meanwhile, the social defeat-induced increases in CRH mRNA in hypothalamus were restored by icaritin administration. Our data also suggests that icaritin administration remarkably attenuated the increases in serum IL-6 and TNF-α level that occur following exposure to social defeat. In conclusion, icaritin is a novel antidepressant. It partially restored social defeat-induced impairment of glucocorticoid sensitivity, HPA axis hyperactivity. These effects are at least partially attributed to normalization of the GR function and increases in BDNF expression. Copyright © 2013 Elsevier B.V. All rights reserved.

Quasi physisorptive two dimensional tungsten oxide nanosheets with extraordinary sensitivity and selectivity to NO2.

PubMed

Khan, Hareem; Zavabeti, Ali; Wang, Yichao; Harrison, Christopher J; Carey, Benjamin J; Mohiuddin, Md; Chrimes, Adam F; De Castro, Isabela Alves; Zhang, Bao Yue; Sabri, Ylias M; Bhargava, Suresh K; Ou, Jian Zhen; Daeneke, Torben; Russo, Salvy P; Li, Yongxiang; Kalantar-Zadeh, Kourosh

2017-12-14

Attributing to their distinct thickness and surface dependent physicochemical properties, two dimensional (2D) nanostructures have become an area of increasing interest for interfacial interactions. Effectively, properties such as high surface-to-volume ratio, modulated surface activities and increased control of oxygen vacancies make these types of materials particularly suitable for gas-sensing applications. This work reports a facile wet-chemical synthesis of 2D tungsten oxide nanosheets by sonication of tungsten particles in an acidic environment and thermal annealing thereafter. The resultant product of large nanosheets with intrinsic substoichiometric properties is shown to be highly sensitive and selective to nitrogen dioxide (NO 2 ) gas, which is a major pollutant. The strong synergy between polar NO 2 molecules and tungsten oxide surface and also abundance of active surface sites on the nanosheets for molecule interactions contribute to the exceptionally sensitive and selective response. An extraordinary response factor of ∼30 is demonstrated to ultralow 40 parts per billion (ppb) NO 2 at a relatively low operating temperature of 150 °C, within the physisorption temperature band for tungsten oxide. Selectivity to NO 2 is demonstrated and the theory behind it is discussed. The structural, morphological and compositional characteristics of the synthesised and annealed materials are extensively characterised and electronic band structures are proposed. The demonstrated 2D tungsten oxide based sensing device holds the greatest promise for producing future commercial low-cost, sensitive and selective NO 2 gas sensors.

Sensitizing of pyrene fluorescence by β-cyclodextrin-modified TiO2 nanoparticles.

PubMed

Shown, Indrajit; Ujihara, Masaki; Imae, Toyoko

2010-12-15

TiO(2) nanoparticles were synthesized by hydrolysis of tetraisopropyl orthotitanate in an aqueous solution of cyclodextrin. The β-cyclodextrin-modified spherical TiO(2) nanoparticles were water-dispersible and had an average particle diameter of 4.4 ± 1 nm. Pyrene fluorescence was enhanced by increasing the concentration of β-cyclodextrin-modified TiO(2) nanoparticle and the sensitization effect was triply stronger than the case of the β-cyclodextrin only. The increase in a concentration of host (β-cyclodextrin) changes its microenvironment for guest (pyrene), that is, the interaction of pyrene with apolar cavity of β-cyclodextrin increases, resulting in enhancement of fluorescence. The sensitization behavior of pyrene fluorescence in the presence of TiO(2) nanoparticles occurs from the increase in the extinction coefficient of pyrene, demonstrating the charge transfer between pyrene and metal oxide nanoparticle. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

Sensitive liquid refractive index sensors using tapered optical fiber tips.

PubMed

Tai, Yi-Hsin; Wei, Pei-Kuen

2010-04-01

An optical fiber sensor based on the change of optical confinement in a subwavelength tip is presented. The optical spot is substantially increased when the environmental refractive index (RI) increases from 1.3 to 1.4. By measuring the intensity of low angular spectral components, an intensity sensitivity up to 8000% per RI unit is achieved. The fiber tip sensors take advantage of the small detection volume and real-time responses. We demonstrate the application of the nanofiber sensors for measuring concentrations of acids and evaporation rates of aqueous mixtures.

Ignoring correlation in uncertainty and sensitivity analysis in life cycle assessment: what is the risk?

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

Groen, E.A., E-mail: Evelyne.Groen@gmail.com; Heijungs, R.; Leiden University, Einsteinweg 2, Leiden 2333 CC

Life cycle assessment (LCA) is an established tool to quantify the environmental impact of a product. A good assessment of uncertainty is important for making well-informed decisions in comparative LCA, as well as for correctly prioritising data collection efforts. Under- or overestimation of output uncertainty (e.g. output variance) will lead to incorrect decisions in such matters. The presence of correlations between input parameters during uncertainty propagation, can increase or decrease the the output variance. However, most LCA studies that include uncertainty analysis, ignore correlations between input parameters during uncertainty propagation, which may lead to incorrect conclusions. Two approaches to include correlationsmore » between input parameters during uncertainty propagation and global sensitivity analysis were studied: an analytical approach and a sampling approach. The use of both approaches is illustrated for an artificial case study of electricity production. Results demonstrate that both approaches yield approximately the same output variance and sensitivity indices for this specific case study. Furthermore, we demonstrate that the analytical approach can be used to quantify the risk of ignoring correlations between input parameters during uncertainty propagation in LCA. We demonstrate that: (1) we can predict if including correlations among input parameters in uncertainty propagation will increase or decrease output variance; (2) we can quantify the risk of ignoring correlations on the output variance and the global sensitivity indices. Moreover, this procedure requires only little data. - Highlights: • Ignoring correlation leads to under- or overestimation of the output variance. • We demonstrated that the risk of ignoring correlation can be quantified. • The procedure proposed is generally applicable in life cycle assessment. • In some cases, ignoring correlation has a minimal effect on decision-making tools.« less

Can Anxiety Tested in the Elevated Plus-maze Be Related to Nociception Sensitivity in Adult Male Rats?

PubMed

Pometlová, Marie; Yamamotová, Anna; Nohejlová, Kateryna; Šlamberová, Romana

Methamphetamine (MA) is one of the most addictive psychostimulant drugs with a high potential for abuse. Our previous studies demonstrated that MA administered to pregnant rats increases pain sensitivity and anxiety in their adult offspring and makes them more sensitive to acute administration of the same drug in adulthood. Because individuals can differ considerably in terms of behaviour and physiology, such as rats that do not belong in some characteristics (e.g. anxiety) to average, can be described as low-responders or high-responders, are then more or less sensitive to pain. Therefore, prenatally MA-exposed adult male rats treated in adulthood with a single dose of MA (1 mg/ml/kg) or saline (1 ml/kg) were tested in the present study. We examined the effect of acute MA treatment on: (1) the anxiety in the Elevated plus-maze (EPM) test and memory in EPM re-test; (2) nociception sensitivity in the Plantar test; (3) the correlation between the anxiety, memory and the nociception. Our results demonstrate that: (1) MA has an anxiogenic effect on animals prenatally exposed to the same drug in the EPM; (2) all the differences induced by acute MA treatment disappeared within the time of 48 hours; (3) there was no effect of MA on nociception per se, but MA induced higher anxiety in individuals less sensitive to pain than in animals more sensitive to pain. In conclusion, the present study demonstrates unique data showing association between anxiety and nociceptive sensitivity of prenatally MA-exposed rats that is induced by acute drug administration.

Increased thermal pain sensitivity in animals exposed to chronic high dose Vicodin but not pure hydrocodone.

PubMed

O'Connell, Thomas F; Carpenter, Patrick S; Caballero, Nadia; Putnam, Andrew J; Steere, Joshua T; Matz, Gregory J; Foecking, Eileen M

2014-01-01

Vicodin, the combination drug of acetaminophen and the opioid hydrocodone, is one of the most prescribed drugs on the market today. Opioids have demonstrated the ability to paradoxically cause increased pain sensitivity to users in a phenomena called opioid-induced hyperalgesia (OIH). While selected opioids have been shown to produce OIH symptoms in an animal model, hydrocodone and the combination drug Vicodin have yet to be studied. The purpose of this study was to explore the effect of exposure to chronic high dose Vicodin or its components on the sensitivity to both thermal and mechanical pain. Animals were randomly divided into 4 groups, Vicodin, acetaminophen, hydrocodone, or vehicle control, and administered the drug daily for 120 days. Rats were subsequently tested for thermal and mechanical sensitivity. The rats in the Vicodin group displayed a significant decrease in withdrawal time to thermal pain. The rats receiving acetaminophen, hydrocodone, and vehicle showed no statistically significant hypersensitivity in thermal testing. None of the groups demonstrated statistically significant hypersensitivity to mechanical testing. The data suggests Vicodin produces signs of OIH in a rodent model. However, increased pain sensitivity was only noted in the thermal pathway and the hypersensitivity was only seen with the opioid combination drug, not the opioid alone. The results of this study both support the results of previous rodent opioid studies while generating further questions about the specific properties of Vicodin that contribute to pain hypersensitivity. The growing use of Vicodin to treat chronic pain necessitates further research looking into this paradoxical pain response.

Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance

PubMed Central

Palanivel, R.; Fullerton, M. D.; Galic, S.; Honeyman, J.; Hewitt, K. A.; Jorgensen, S. B.; Steinberg, G. R.

2017-01-01

Aims/hypothesis Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known. Methods We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed. Results The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic–euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1). Conclusions/interpretation These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity. PMID:22872213

Sensitivity of medial and lateral knee contact force predictions to frontal plane alignment and contact locations.

PubMed

Saliba, Christopher M; Brandon, Scott C E; Deluzio, Kevin J

2017-05-24

Musculoskeletal models are increasingly used to estimate medial and lateral knee contact forces, which are difficult to measure in vivo. The sensitivity of contact force predictions to modeling parameters is important to the interpretation and implication of results generated by the model. The purpose of this study was to quantify the sensitivity of knee contact force predictions to simultaneous errors in frontal plane knee alignment and contact locations under different dynamic conditions. We scaled a generic musculoskeletal model for N=23 subjects' stature and radiographic knee alignment, then perturbed frontal plane alignment and mediolateral contact locations within experimentally-possible ranges of 10° to -10° and 10 to -10mm, respectively. The sensitivity of first peak, second peak, and mean medial and lateral knee contact forces to knee adduction angle and contact locations was modeled using linear regression. Medial loads increased, and lateral loads decreased, by between 3% and 6% bodyweight for each degree of varus perturbation. Shifting the medial contact point medially increased medial loads and decreased lateral loads by between 1% and 4% bodyweight per millimeter. This study demonstrates that realistic measurement errors of 5mm (contact distance) or 5° (frontal plane alignment) could result in a combined 50% BW error in subject specific contact force estimates. We also show that model sensitivity varies between subjects as a result of differences in gait dynamics. These results demonstrate that predicted knee joint contact forces should be considered as a range of possible values determined by model uncertainty. Copyright © 2017 Elsevier Ltd. All rights reserved.

Large area graphene ion sensitive field effect transistors with tantalum pentoxide sensing layers for pH measurement at the Nernstian limit

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

Fakih, Ibrahim, E-mail: ibrahim.fakih@mail.mcgill.ca; Sabri, Shadi; Szkopek, Thomas, E-mail: thomas.szkopek@mcgill.ca

2014-08-25

We have fabricated and characterized large area graphene ion sensitive field effect transistors (ISFETs) with tantalum pentoxide sensing layers and demonstrated pH sensitivities approaching the Nernstian limit. Low temperature atomic layer deposition was used to deposit tantalum pentoxide atop large area graphene ISFETs. The charge neutrality point of graphene, inferred from quantum capacitance or channel conductance, was used to monitor surface potential in the presence of an electrolyte with varying pH. Bare graphene ISFETs exhibit negligible response, while graphene ISFETs with tantalum pentoxide sensing layers show increased sensitivity reaching up to 55 mV/pH over pH 3 through pH 8. Applying themore » Bergveld model, which accounts for site binding and a Guoy-Chapman-Stern picture of the surface-electrolyte interface, the increased pH sensitivity can be attributed to an increased buffer capacity reaching up to 10{sup 14} sites/cm{sup 2}. ISFET response was found to be stable to better than 0.05 pH units over the course of two weeks.« less

Large area graphene ion sensitive field effect transistors with tantalum pentoxide sensing layers for pH measurement at the Nernstian limit

NASA Astrophysics Data System (ADS)

Fakih, Ibrahim; Sabri, Shadi; Mahvash, Farzaneh; Nannini, Matthieu; Siaj, Mohamed; Szkopek, Thomas

2014-08-01

We have fabricated and characterized large area graphene ion sensitive field effect transistors (ISFETs) with tantalum pentoxide sensing layers and demonstrated pH sensitivities approaching the Nernstian limit. Low temperature atomic layer deposition was used to deposit tantalum pentoxide atop large area graphene ISFETs. The charge neutrality point of graphene, inferred from quantum capacitance or channel conductance, was used to monitor surface potential in the presence of an electrolyte with varying pH. Bare graphene ISFETs exhibit negligible response, while graphene ISFETs with tantalum pentoxide sensing layers show increased sensitivity reaching up to 55 mV/pH over pH 3 through pH 8. Applying the Bergveld model, which accounts for site binding and a Guoy-Chapman-Stern picture of the surface-electrolyte interface, the increased pH sensitivity can be attributed to an increased buffer capacity reaching up to 1014 sites/cm2. ISFET response was found to be stable to better than 0.05 pH units over the course of two weeks.

A role for tyrosinase-related protein 1 in 4-tert-butylphenol-induced toxicity in melanocytes: Implications for vitiligo.

PubMed

Manga, Prashiela; Sheyn, David; Yang, Fan; Sarangarajan, Rangaprasad; Boissy, Raymond E

2006-11-01

Vitiligo presents with depigmented cutaneous lesions following localized melanocyte death. Multiple factors contribute to cell death, including genetically determined susceptibility to trauma, and environmental factors, such as exposure to 4-tert-butylphenol (4-TBP). We demonstrate that 4-TBP induces oxidative stress that is more readily overcome by melanocytes from normally pigmented individuals than from two individuals with vitiligo. The antioxidant catalase selectively and significantly reduced death of melanocytes derived from two individuals with vitiligo, indicating a role for oxidative stress in vitiligo pathogenesis. In normal melanocytes, oxidative stress results in reduced expression of microphthalmia-associated transcription factor (MITF). Melanocyte-stimulating hormone-induced expression of MITF protein caused increased sensitivity to 4-TBP, whereas sensitivity of melanomas correlated with MITF expression. MITF stimulates melanin synthesis by up-regulating expression of melanogenic enzymes such as tyrosinase-related protein-1 (Tyrp1). Although melanin content per se did not affect sensitivity to 4-TBP, expression of Tyrp1 significantly increased sensitivity. Melanocytes and melanomas that express functional Tyrp1 were significantly more sensitive to 4-TBP than Tyrp1-null cells. Thus, normal melanocytes respond to 4-TBP by reducing expression of MITF and Tyrp1. We hypothesize that melanocytes in vitiligo demonstrate reduced ability to withstand oxidative stress due, partly, to a disruption in MITF regulation of Tyrp1.

A single exposure to particulate or gaseous air pollution increases the risk of aconitine-induced cardiac arrythmia in hypertensive rats

EPA Science Inventory

Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

Aconitine Challenge Test Reveals a Single Exposure to Air Pollution Causes Increased Cardiac Arrhythmia Risk in Hypertensive Rats - Abstract

EPA Science Inventory

Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

"Lollipop-shaped" high-sensitivity Microelectromechanical Systems vector hydrophone based on Parylene encapsulation

NASA Astrophysics Data System (ADS)

Liu, Yuan; Wang, Renxin; Zhang, Guojun; Du, Jin; Zhao, Long; Xue, Chenyang; Zhang, Wendong; Liu, Jun

2015-07-01

This paper presents methods of promoting the sensitivity of Microelectromechanical Systems (MEMS) vector hydrophone by increasing the sensing area of cilium and perfect insulative Parylene membrane. First, a low-density sphere is integrated with the cilium to compose a "lollipop shape," which can considerably increase the sensing area. A mathematic model on the sensitivity of the "lollipop-shaped" MEMS vector hydrophone is presented, and the influences of different structural parameters on the sensitivity are analyzed via simulation. Second, the MEMS vector hydrophone is encapsulated through the conformal deposition of insulative Parylene membrane, which enables underwater acoustic monitoring without any typed sound-transparent encapsulation. Finally, the characterization results demonstrate that the sensitivity reaches up to -183 dB (500 Hz 0dB at 1 V/ μPa ), which is increased by more than 10 dB, comparing with the previous cilium-shaped MEMS vector hydrophone. Besides, the frequency response takes on a sensitivity increment of 6 dB per octave. The working frequency band is 20-500 Hz and the concave point depth of 8-shaped directivity is beyond 30 dB, indicating that the hydrophone is promising in underwater acoustic application.

Complex-valued time-series correlation increases sensitivity in FMRI analysis.

PubMed

Kociuba, Mary C; Rowe, Daniel B

2016-07-01

To develop a linear matrix representation of correlation between complex-valued (CV) time-series in the temporal Fourier frequency domain, and demonstrate its increased sensitivity over correlation between magnitude-only (MO) time-series in functional MRI (fMRI) analysis. The standard in fMRI is to discard the phase before the statistical analysis of the data, despite evidence of task related change in the phase time-series. With a real-valued isomorphism representation of Fourier reconstruction, correlation is computed in the temporal frequency domain with CV time-series data, rather than with the standard of MO data. A MATLAB simulation compares the Fisher-z transform of MO and CV correlations for varying degrees of task related magnitude and phase amplitude change in the time-series. The increased sensitivity of the complex-valued Fourier representation of correlation is also demonstrated with experimental human data. Since the correlation description in the temporal frequency domain is represented as a summation of second order temporal frequencies, the correlation is easily divided into experimentally relevant frequency bands for each voxel's temporal frequency spectrum. The MO and CV correlations for the experimental human data are analyzed for four voxels of interest (VOIs) to show the framework with high and low contrast-to-noise ratios in the motor cortex and the supplementary motor cortex. The simulation demonstrates the increased strength of CV correlations over MO correlations for low magnitude contrast-to-noise time-series. In the experimental human data, the MO correlation maps are noisier than the CV maps, and it is more difficult to distinguish the motor cortex in the MO correlation maps after spatial processing. Including both magnitude and phase in the spatial correlation computations more accurately defines the correlated left and right motor cortices. Sensitivity in correlation analysis is important to preserve the signal of interest in fMRI data sets with high noise variance, and avoid excessive processing induced correlation. Copyright © 2016 Elsevier Inc. All rights reserved.

[Sensitization and oral challenge with ovoalbumin in an animal model of food allergy].

PubMed

Vinuesa, Miguel Ngel; Bassan, Norberto David; Chaparro, Soledad; Martìnez, Adriel; Batle, Rocìo; Giacomozzi, Florencia; Torres, Valentìn

2012-01-01

Gut-associated lymphoid tissue (GALT) is mainly formed by the gut mucosa and associated lymphatic structures that under normal conditions induces hyporesponsiveness, a phenomenon termed oral tolerance. However, the potential brakeup of oral tolerance could otherwise lead to disorders such as food allergy. The aim of the study is to characterise the histopathological and immunohistochemical modifications in intestinal gut mucosa in an animal model of food allergy. New Zealand rabbits were subcutaneously sensitized twice with ovalbumin (OVA), on day 30 after first sensitization, animals were oral challenged with the same antigen. Lymphatic cell population and accessory cells from gut mucosa were studied by conventional histology, histochemistry and immunohistochemistry. An important increase in number of eosinophils were observed in sensitized and challenged group as well as CD25+cells increase in sensitized animals without challenge. Data obtained demonstrated that subcutaneous sensitization and challenge with OVA induced generation of specific IgE antibodies and an anaphylactic inflammatory response. This pattern induced quantitative modifications in studied cells and structural changes in mucosa like oedema at intestinal villi in sensitized and challenged rabbits in this animal model of food allergy.

λ/26 silver nanodots fabricated by direct laser writing through highly sensitive two-photon photoreduction

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

Cao, Yaoyu; Gu, Min, E-mail: mgu@swin.edu.au

We demonstrated an approach to break the diffraction limit and realise deep-subwavelength two-photon direct laser writing by employing a highly sensitive photoreduction process. The photoreduction photosensitivity increased by at least 4 times while the wavelength of the fabrication laser beam was tuned from 800 nm to 580 nm. The increase of the photosensitivity resulted in improved resolution for the silver dot fabrication. By developing the photoreduction material with adding electron donors, the photosensitivity further increased and enabled the realisation of a single silver dot at 22 nm which is λ/26 for the wavelength of the fabrication laser beam.

Analysis of Publically Available Skin Sensitization Data from REACH Registrations 2008–2014

PubMed Central

Luechtefeld, Thomas; Maertens, Alexandra; Russo, Daniel P.; Rovida, Costanza; Zhu, Hao; Hartung, Thomas

2017-01-01

Summary The public data on skin sensitization from REACH registrations already included 19,111 studies on skin sensitization in December 2014, making it the largest repository of such data so far (1,470 substances with mouse LLNA, 2,787 with GPMT, 762 with both in vivo and in vitro and 139 with only in vitro data). 21% were classified as sensitizers. The extracted skin sensitization data was analyzed to identify relationships in skin sensitization guidelines, visualize structural relationships of sensitizers, and build models to predict sensitization. A chemical with molecular weight > 500 Da is generally considered non-sensitizing owing to low bioavailability, but 49 sensitizing chemicals with a molecular weight > 500 Da were found. A chemical similarity map was produced using PubChem’s 2D Tanimoto similarity metric and Gephi force layout visualization. Nine clusters of chemicals were identified by Blondel’s module recognition algorithm revealing wide module-dependent variation. Approximately 31% of mapped chemicals are Michael’s acceptors but alone this does not imply skin sensitization. A simple sensitization model using molecular weight and five ToxTree structural alerts showed a balanced accuracy of 65.8% (specificity 80.4%, sensitivity 51.4%), demonstrating that structural alerts have information value. A simple variant of k-nearest neighbors outperformed the ToxTree approach even at 75% similarity threshold (82% balanced accuracy at 0.95 threshold). At higher thresholds, the balanced accuracy increased. Lower similarity thresholds decrease sensitivity faster than specificity. This analysis scopes the landscape of chemical skin sensitization, demonstrating the value of large public datasets for health hazard prediction. PMID:26863411

Impact of substrate etching on plasmonic elements and metamaterials: preventing red shift and improving refractive index sensitivity.

PubMed

Moritake, Yuto; Tanaka, Takuo

2018-02-05

We propose and demonstrate the elimination of substrate influence on plasmon resonance by using selective and isotropic etching of substrates. Preventing the red shift of the resonance due to substrates and improving refractive index sensitivity were experimentally demonstrated by using plasmonic nanostructures fabricated on silicon substrates. Applying substrate etching decreases the effective refractive index around the metal nanostructures, resulting in elimination of the red shift. Improvement of sensitivity to the refractive index environment was demonstrated by using plasmonic metamaterials with Fano resonance based on far field interference. Change in quality factors (Q-factors) of the Fano resonance by substrate etching was also investigated in detail. The presence of a closely positioned substrate distorts the electric field distribution and degrades the Q-factors. Substrate etching dramatically increased the refractive index sensitivity reaching to 1532 nm/RIU since the electric fields under the nanostructures became accessible through substrate etching. The FOM was improved compared to the case without the substrate etching. The method presented in this paper is applicable to a variety of plasmonic structures to eliminate the influence of substrates for realizing high performance plasmonic devices.

Activation of β-adrenergic receptors is required for elevated α1A-adrenoreceptors expression and signaling in mesenchymal stromal cells

PubMed Central

Tyurin-Kuzmin, Pyotr A.; Fadeeva, Julia I.; Kanareikina, Margarita A.; Kalinina, Natalia I.; Sysoeva, Veronika Yu.; Dyikanov, Daniyar T.; Stambolsky, Dmitriy V.; Tkachuk, Vsevolod A.

2016-01-01

Sympathetic neurons are important components of mesenchymal stem cells (MSCs) niche and noradrenaline regulates biological activities of these cells. Here we examined the mechanisms of regulation of MSCs responsiveness to noradrenaline. Using flow cytometry, we demonstrated that α1A adrenergic receptors isoform was the most abundant in adipose tissue-derived MSCs. Using calcium imaging in single cells, we demonstrated that only 6.9 ± 0.8% of MSCs responded to noradrenaline by intracellular calcium release. Noradrenaline increases MSCs sensitivity to catecholamines in a transitory mode. Within 6 hrs after incubation with noradrenaline the proportion of cells responding by Ca2+ release to the fresh noradrenaline addition has doubled but declined to the baseline after 24 hrs. Increased sensitivity was due to the elevated quantities of α1A-adrenergic receptors on MSCs. Such elevation depended on the stimulation of β-adrenergic receptors and adenylate cyclase activation. The data for the first time clarify mechanisms of regulation of MSCs sensitivity to noradrenaline. PMID:27596381

Agaricus blazei Murill enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells by NFκB-mediated increase of intracellular doxorubicin accumulation.

PubMed

Lee, Jong Seok; Hong, Eock Kee

2011-02-01

It has been demonstrated that the Agaricus blazei Murill (ABM) mushroom, which primarily consists of polysaccharides, possesses anti-tumor activities. However, the mechanisms by which ABM inhibits human hepatocellular carcinoma growth remain unknown. Our study demonstrates that ABM acts as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this sensitization can be achieved by enhancing intracellular Dox accumulation via the inhibition of NFκB activity. These findings suggest that ABM, when combined with low doses of Dox, has the potential to provide more efficient therapeutic effects against drug-resistant human hepatocellular carcinoma.

Glutathione depletion prevents diet-induced obesity and enhances insulin sensitivity.

PubMed

Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L; Cohn, Dianne; Heywood, Elizabeth B; Bruemmer, Dennis

2011-12-01

Excessive accumulation of reactive oxygen species (ROS) in adipose tissue has been implicated in the development of insulin resistance and type 2 diabetes. However, emerging evidence suggests a physiologic role of ROS in cellular signaling and insulin sensitivity. In this study, we demonstrate that pharmacologic depletion of the antioxidant glutathione in mice prevents diet-induced obesity, increases energy expenditure and locomotor activity, and enhances insulin sensitivity. These observations support a beneficial role of ROS in glucose homeostasis and warrant further research to define the regulation of metabolism and energy balance by ROS.

Confocal imaging of transmembrane voltage by SEER of di-8-ANEPPS

PubMed Central

Manno, Carlo; Figueroa, Lourdes; Fitts, Robert

2013-01-01

Imaging, optical mapping, and optical multisite recording of transmembrane potential (Vm) are essential for studying excitable cells and systems. The naphthylstyryl voltage-sensitive dyes, including di-8-ANEPPS, shift both their fluorescence excitation and emission spectra upon changes in Vm. Accordingly, they have been used for monitoring Vm in nonratioing and both emission and excitation ratioing modes. Their changes in fluorescence are usually much less than 10% per 100 mV. Conventional ratioing increases sensitivity to between 3 and 15% per 100 mV. Low sensitivity limits the value of these dyes, especially when imaged with low light systems like confocal scanners. Here we demonstrate the improvement afforded by shifted excitation and emission ratioing (SEER) as applied to imaging membrane potential in flexor digitorum brevis muscle fibers of adult mice. SEER—the ratioing of two images of fluorescence, obtained with different excitation wavelengths in different emission bands—was implemented in two commercial confocal systems. A conventional pinhole scanner, affording optimal setting of emission bands but less than ideal excitation wavelengths, achieved a sensitivity of up to 27% per 100 mV, nearly doubling the value found by conventional ratioing of the same data. A better pair of excitation lights should increase the sensitivity further, to 35% per 100 mV. The maximum acquisition rate with this system was 1 kHz. A fast “slit scanner” increased the effective rate to 8 kHz, but sensitivity was lower. In its high-sensitivity implementation, the technique demonstrated progressive deterioration of action potentials upon fatiguing tetani induced by stimulation patterns at >40 Hz, thereby identifying action potential decay as a contributor to fatigue onset. Using the fast implementation, we could image for the first time an action potential simultaneously at multiple locations along the t-tubule system. These images resolved the radially varying lag associated with propagation at a finite velocity. PMID:23440278

Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

PubMed

Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D

2016-01-15

Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension. Copyright © 2016 the American Physiological Society.

Confocal imaging of transmembrane voltage by SEER of di-8-ANEPPS.

PubMed

Manno, Carlo; Figueroa, Lourdes; Fitts, Robert; Ríos, Eduardo

2013-03-01

Imaging, optical mapping, and optical multisite recording of transmembrane potential (V(m)) are essential for studying excitable cells and systems. The naphthylstyryl voltage-sensitive dyes, including di-8-ANEPPS, shift both their fluorescence excitation and emission spectra upon changes in V(m). Accordingly, they have been used for monitoring V(m) in nonratioing and both emission and excitation ratioing modes. Their changes in fluorescence are usually much less than 10% per 100 mV. Conventional ratioing increases sensitivity to between 3 and 15% per 100 mV. Low sensitivity limits the value of these dyes, especially when imaged with low light systems like confocal scanners. Here we demonstrate the improvement afforded by shifted excitation and emission ratioing (SEER) as applied to imaging membrane potential in flexor digitorum brevis muscle fibers of adult mice. SEER--the ratioing of two images of fluorescence, obtained with different excitation wavelengths in different emission bands-was implemented in two commercial confocal systems. A conventional pinhole scanner, affording optimal setting of emission bands but less than ideal excitation wavelengths, achieved a sensitivity of up to 27% per 100 mV, nearly doubling the value found by conventional ratioing of the same data. A better pair of excitation lights should increase the sensitivity further, to 35% per 100 mV. The maximum acquisition rate with this system was 1 kHz. A fast "slit scanner" increased the effective rate to 8 kHz, but sensitivity was lower. In its high-sensitivity implementation, the technique demonstrated progressive deterioration of action potentials upon fatiguing tetani induced by stimulation patterns at >40 Hz, thereby identifying action potential decay as a contributor to fatigue onset. Using the fast implementation, we could image for the first time an action potential simultaneously at multiple locations along the t-tubule system. These images resolved the radially varying lag associated with propagation at a finite velocity.

Tapered GRIN fiber microsensor.

PubMed

Beltrán-Mejía, Felipe; Biazoli, Claudecir R; Cordeiro, Cristiano M B

2014-12-15

The sensitivity of an optical fiber microsensor based on inter-modal interference can be considerably improved by tapering a short extension of the multimode fiber. In the case of Graded Index fibers with a parabolic refractive index profile, a meridional ray exhibits a sinusoidal path. When these fibers are tapered, the period of the propagated beam decrease down-taper and increase up-taper. We take advantage of this modulation -along with the enhanced overlap between the evanescent field and the external medium- to substantially increase the sensitivity of these devices by tuning the sensor's maximum sensitivity wavelength. Moreover, the extension of this device is reduced by one order of magnitude, making it more propitious for reduced space applications. Numerical and experimental results demonstrate the success and feasibility of this approach.

Evaluation of Porous Silicon Oxide on Silicon Microcantilevers for Sensitive Detection of Gaseous HF.

PubMed

Wallace, Ryan A; Sepaniak, Michael J; Lavrik, Nickolay V; Datskos, Panos G

2017-06-06

Sensitive detection of harmful chemicals in industrial applications is pertinent to safety. In this work, we demonstrate the use of a sensitive silicon microcantilever (MC) system with a porous silicon oxide layer deposited on the active side of the MCs that have been mechanically manipulated to increase sensitivity. Included is the evaluation of porous silicon oxide present on different geometries of MCs and exposed to varying concentrations of hydrogen fluoride in humid air. Profilometry and the signal generated by the stress-induced porous silicon oxide (PSO) coating and bending of the MC were used as methods of evaluation.

Evaluation of Porous Silicon Oxide on Silicon Microcantilevers for Sensitive Detection of Gaseous HF

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

Wallace, Ryan A.; Sepaniak, Michael J.; Lavrik, Nickolay V.

Sensitive detection of harmful chemicals in industrial applications is pertinent to safety. In this paper, we demonstrate the use of a sensitive silicon microcantilever (MC) system with a porous silicon oxide layer deposited on the active side of the MCs that have been mechanically manipulated to increase sensitivity. Included is the evaluation of porous silicon oxide present on different geometries of MCs and exposed to varying concentrations of hydrogen fluoride in humid air. Finally, profilometry and the signal generated by the stress-induced porous silicon oxide (PSO) coating and bending of the MC were used as methods of evaluation.

Sensitivity, accuracy, and precision issues in opto-electronic holography based on fiber optics and high-spatial- and high-digitial-resolution cameras

NASA Astrophysics Data System (ADS)

Furlong, Cosme; Yokum, Jeffrey S.; Pryputniewicz, Ryszard J.

2002-06-01

Sensitivity, accuracy, and precision characteristics in quantitative optical metrology techniques, and specifically in optoelectronic holography based on fiber optics and high-spatial and high-digital resolution cameras, are discussed in this paper. It is shown that sensitivity, accuracy, and precision dependent on both, the effective determination of optical phase and the effective characterization of the illumination-observation conditions. Sensitivity, accuracy, and precision are investigated with the aid of National Institute of Standards and Technology (NIST) traceable gages, demonstrating the applicability of quantitative optical metrology techniques to satisfy constantly increasing needs for the study and development of emerging technologies.

Evaluation of Porous Silicon Oxide on Silicon Microcantilevers for Sensitive Detection of Gaseous HF

DOE PAGES

Wallace, Ryan A.; Sepaniak, Michael J.; Lavrik, Nickolay V.; ...

2017-05-10

Sensitive detection of harmful chemicals in industrial applications is pertinent to safety. In this paper, we demonstrate the use of a sensitive silicon microcantilever (MC) system with a porous silicon oxide layer deposited on the active side of the MCs that have been mechanically manipulated to increase sensitivity. Included is the evaluation of porous silicon oxide present on different geometries of MCs and exposed to varying concentrations of hydrogen fluoride in humid air. Finally, profilometry and the signal generated by the stress-induced porous silicon oxide (PSO) coating and bending of the MC were used as methods of evaluation.

Highly sensitive, self-powered and wearable electronic skin based on pressure-sensitive nanofiber woven fabric sensor.

PubMed

Zhou, Yuman; He, Jianxin; Wang, Hongbo; Qi, Kun; Nan, Nan; You, Xiaolu; Shao, Weili; Wang, Lidan; Ding, Bin; Cui, Shizhong

2017-10-11

The wearable electronic skin with high sensitivity and self-power has shown increasing prospects for applications such as human health monitoring, robotic skin, and intelligent electronic products. In this work, we introduced and demonstrated a design of highly sensitive, self-powered, and wearable electronic skin based on a pressure-sensitive nanofiber woven fabric sensor fabricated by weaving PVDF electrospun yarns of nanofibers coated with PEDOT. Particularly, the nanofiber woven fabric sensor with multi-leveled hierarchical structure, which significantly induced the change in contact area under ultra-low load, showed combined superiority of high sensitivity (18.376 kPa -1 , at ~100 Pa), wide pressure range (0.002-10 kPa), fast response time (15 ms) and better durability (7500 cycles). More importantly, an open-circuit voltage signal of the PPNWF pressure sensor was obtained through applying periodic pressure of 10 kPa, and the output open-circuit voltage exhibited a distinct switching behavior to the applied pressure, indicating the wearable nanofiber woven fabric sensor could be self-powered under an applied pressure. Furthermore, we demonstrated the potential application of this wearable nanofiber woven fabric sensor in electronic skin for health monitoring, human motion detection, and muscle tremor detection.

Low level lead exposure: history and discovery.

PubMed

Needleman, Herbert

2009-04-01

The history of lead toxicity spans 2 millennnia. With increasingly sensitive methods, deficits due to lead exposure have been demonstrated at lower and lower doses. Persuasive evidence suggests that no threshold for lead toxicity exists.

Acid-sensitive sheddable PEGylated, mannose-modified nanoparticles increase the delivery of betamethasone to chronic inflammation sites in a mouse model

PubMed Central

O’Mary, Hannah L.; Aldayel, Abdulaziz M.; Valdes, Solange A.; Naguib, Youssef W.; Li, Xu; Salvady, Karun; Cui, Zhengrong

2017-01-01

Inflammation is implicated in a host of chronic illnesses. Within these inflamed tissues, the pH of the microenvironment is decreased and immune cells, particularly macrophages, infiltrate the area. Additionally, the vascular integrity of these sites is altered with increased fenestrations between endothelial cells. These distinctive properties may be exploited to enhance targeted delivery of anti-inflammatory therapies. Using a mouse model of chronic inflammation, we previously showed that acid-sensitive sheddable PEGylation increases the distribution and retention of nanoparticles in chronic inflammation sites. Here we demonstrated that surface modification of the acid-sensitive sheddable PEGylated nanoparticles with mannose, a ligand to mannose receptors present in chronic inflammation sites, significantly increases the targeted delivery of the nanoparticles to these areas. Furthermore, we showed that the acid-sensitive sheddable PEGylated, mannose-modified nanoparticles are able to significantly increase the delivery of betamethasone-21-acetate (BA), a model anti-inflammatory compound, to chronic inflammation sites as compared to free BA. These results highlight the ability to engineer formulations to target chronic inflammation sites by exploiting the microenvironment of these regions. PMID:28463518

Role of Resistant Starch in Improving Gut Health, Adiposity, and Insulin Resistance1234

PubMed Central

Keenan, Michael J; Zhou, June; Hegsted, Maren; Pelkman, Christine; Durham, Holiday A; Coulon, Diana B; Martin, Roy J

2015-01-01

The realization that low–glycemic index diets were formulated using resistant starch led to more than a decade of research on the health effects of resistant starch. Determination of the metabolizable energy of the resistant starch product allowed for the performance of isocaloric studies. Fermentation of resistant starch in rodent studies results in what appears to be a healthier gut, demonstrated by increased amounts of short-chain fatty acids, an apparent positive change in the microbiota, and increased gene expression for gene products involved in normal healthy proliferation and apoptosis of potential cancer cells. Additionally, consumption of resistant starch was associated with reduced abdominal fat and improved insulin sensitivity. Increased serum glucagon-like peptide 1 (GLP-1) likely plays a role in promoting these health benefits. One rodent study that did not use isocaloric diets demonstrated that the use of resistant starch at 8% of the weight of the diet reduced body fat. This appears to be approximately equivalent to the human fiber requirement. In human subjects, insulin sensitivity is increased with the feeding of resistant starch. However, only 1 of several studies reports an increase in serum GLP-1 associated with resistant starch added to the diet. This means that other mechanisms, such as increased intestinal gluconeogenesis or increased adiponectin, may be involved in the promotion of improved insulin sensitivity. Future research may confirm that there will be improved health if human individuals consume the requirement for dietary fiber and a large amount of the fiber is fermentable. PMID:25770258

Role of resistant starch in improving gut health, adiposity, and insulin resistance.

PubMed

Keenan, Michael J; Zhou, June; Hegsted, Maren; Pelkman, Christine; Durham, Holiday A; Coulon, Diana B; Martin, Roy J

2015-03-01

The realization that low-glycemic index diets were formulated using resistant starch led to more than a decade of research on the health effects of resistant starch. Determination of the metabolizable energy of the resistant starch product allowed for the performance of isocaloric studies. Fermentation of resistant starch in rodent studies results in what appears to be a healthier gut, demonstrated by increased amounts of short-chain fatty acids, an apparent positive change in the microbiota, and increased gene expression for gene products involved in normal healthy proliferation and apoptosis of potential cancer cells. Additionally, consumption of resistant starch was associated with reduced abdominal fat and improved insulin sensitivity. Increased serum glucagon-like peptide 1 (GLP-1) likely plays a role in promoting these health benefits. One rodent study that did not use isocaloric diets demonstrated that the use of resistant starch at 8% of the weight of the diet reduced body fat. This appears to be approximately equivalent to the human fiber requirement. In human subjects, insulin sensitivity is increased with the feeding of resistant starch. However, only 1 of several studies reports an increase in serum GLP-1 associated with resistant starch added to the diet. This means that other mechanisms, such as increased intestinal gluconeogenesis or increased adiponectin, may be involved in the promotion of improved insulin sensitivity. Future research may confirm that there will be improved health if human individuals consume the requirement for dietary fiber and a large amount of the fiber is fermentable. © 2015 American Society for Nutrition.

Serine/threonine protein phosphatase 6 modulates the radiation sensitivity of glioblastoma

PubMed Central

Shen, Y; Wang, Y; Sheng, K; Fei, X; Guo, Q; Larner, J; Kong, X; Qiu, Y; Mi, J

2011-01-01

Increasing the sensitivity of glioblastoma cells to radiation is a promising approach to improve survival in patients with glioblastoma multiforme (GBM). This study aims to determine if serine/threonine phosphatase (protein phosphatase 6 (PP6)) is a molecular target for GBM radiosensitization treatment. The GBM orthotopic xenograft mice model was used in this study. Our data demonstrated that the protein level of PP6 catalytic subunit (PP6c) was upregulated in the GBM tissue from about 50% patients compared with the surrounding tissue or control tissue. Both the in vitro survival fraction of GBM cells and the patient survival time were highly correlated or inversely correlated with PP6c expression (R2=0.755 and −0.707, respectively). We also found that siRNA knockdown of PP6c reduced DNA-dependent protein kinase (DNA-PK) activity in three different GBM cell lines, increasing their sensitivity to radiation. In the orthotopic mice model, the overexpression of PP6c in GBM U87 cells attenuated the effect of radiation treatment, and reduced the survival time of mice compared with the control mice, while the PP6c knocking-down improved the effect of radiation treatment, and increased the survival time of mice. These findings demonstrate that PP6 regulates the sensitivity of GBM cells to radiation, and suggest small molecules disrupting or inhibiting PP6 association with DNA-PK is a potential radiosensitizer for GBM. PMID:22158480

Thermal and chemical treatment of polymer optical fiber Bragg grating sensors for enhanced mechanical sensitivity

NASA Astrophysics Data System (ADS)

Pospori, A.; Marques, C. A. F.; Sáez-Rodríguez, D.; Nielsen, K.; Bang, O.; Webb, D. J.

2017-07-01

An investigation of the thermal annealing effects on the strain, stress, and force sensitivities of polymer optical fiber Bragg grating sensors is performed. We demonstrate for the first time that the fiber annealing can enhance both stress and force sensitivities of Bragg grating sensors, with the possible cause being the molecular relaxation of the polymer when fiber is raised above the β -transition temperature. A simple, cost-effective, but well controlled method for fiber annealing is also presented in this work. In addition, the effects of chemical etching on the strain, stress, and force sensitivities have been investigated. Results show that fiber etching too can increase the force sensitivity, and it can also affect the strain and stress sensitivities of the Bragg grating sensors.

When stress gets into your head: Socioeconomic risk, executive functions, and maternal sensitivity across childrearing contexts.

PubMed

Sturge-Apple, Melissa L; Jones, Hannah R; Suor, Jennifer H

2017-03-01

Socioeconomic adversity has been targeted as a key upstream mechanism with robust pathogenic effects on maternal caregiving. Although research has demonstrated the negative repercussions of socioeconomic difficulties, little research has documented potential mechanisms underlying this association. Toward increasing understanding, the present study examined how maternal working memory capacity and inhibitory control may mediate associations between socioeconomic risk and change in maternal sensitivity across free-play and discipline caregiving contexts. This study used a longitudinal design, and utilized a socioeconomically diverse sample of 185 mothers and their 3.5-year-old toddlers. Multi-informants and methods were used to assess constructs. Findings revealed that maternal EF mediated associations between socioeconomic risk and parenting sensitivity with specific effects for working memory and baseline sensitivity and inhibitory control and change in sensitivity as childrearing demands increased. Results are interpreted within emerging conceptual frameworks regarding the role of parental neurocognitive functioning and caregiving. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The phosphoenolpyruvate:sugar phosphotransferase system is involved in sensitivity to the glucosylated bacteriocin sublancin.

PubMed

Garcia De Gonzalo, C V; Denham, E L; Mars, R A T; Stülke, J; van der Donk, W A; van Dijl, J M

2015-11-01

The mode of action of a group of glycosylated antimicrobial peptides known as glycocins remains to be elucidated. In the current study of one glycocin, sublancin, we identified the phosphoenolpyruvate:sugar phosphotransferase system (PTS) of Bacillus species as a key player in bacterial sensitivity. Sublancin kills several Gram-positive bacteria, such as Bacillus species and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Unlike other classes of bacteriocins for which the PTS is involved in their mechanism of action, we show that the addition of PTS-requiring sugars leads to increased resistance rather than increased sensitivity, suggesting that sublancin has a distinct mechanism of action. Collectively, our present mutagenesis and genomic studies demonstrate that the histidine-containing phosphocarrier protein (HPr) and domain A of enzyme II (PtsG) in particular are critical determinants for bacterial sensitivity to sublancin. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Parasympathetic activation by pyridostigmine on chemoreflex sensitivity in heart-failure rats.

PubMed

Sabino, João Paulo J; da Silva, Carlos Alberto Aguiar; Giusti, Humberto; Glass, Mogens Lesner; Salgado, Helio C; Fazan, Rubens

2013-12-01

We evaluated the effects of parasympathetic activation by pyridostigmine (PYR) on chemoreflex sensitivity in a rat model of heart failure (HF rats). HF rats demonstrated higher pulmonary ventilation (PV), which was not affected by PYR. When HF and control rats treated or untreated with PYR were exposed to 15% O2, all groups exhibited prompt increases in respiratory frequency (RF), tidal volume (TV) and PV. When HF rats were exposed to 10% O2 they showed greater PV response which was prevented by PYR. The hypercapnia triggered by either 5% CO2 or 10% CO2 promoted greater RF and PV responses in HF rats. PYR blunted the RF response in HF rats but did not affect the PV response. In conclusion, PYR prevented increased peripheral chemoreflex sensitivity, partially blunted central chemoreflex sensitivity and did not affect basal PV in HF rats. © 2013.

SAW Humidity Sensor Sensitivity Enhancement via Electrospraying of Silver Nanowires

PubMed Central

Sayar Irani, Farid; Tunaboylu, Bahadir

2016-01-01

In this research, we investigated the influence of the surface coatings of silver nanowires on the sensitivity of surface acoustic wave (SAW) humidity sensors. Silver nanowires, with poly(vinylpyrrolidone) (PVP), which is a hydrophilic capping agent, were chemically synthesized, with an average length of 15 µm and an average diameter of 60 nm. Humidity sensors, with 433 MHz frequency dual-port resonator Rayleigh-SAW devices, were coated by silver nanowires (AgNWs) using the electrospray coating method. It was demonstrated that increasing thickness of coated AgNW on the surfaces of SAW devices results in increased sensitivity. The highest frequency shift (262 kHz) in these SAW devices was obtained with an injection of 0.5 mL of the AgNW solution with a concentration of 0.5 mg/mL at an injection rate of 1 mL/h. It also showed the highest humidity sensitivity among the other prepared SAW devices. PMID:27916870

Biomarkers of exposure, sensitivity and disease

NASA Technical Reports Server (NTRS)

Brooks, A. L.

1999-01-01

PURPOSE: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. OVERVIEW: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. OUTLINE: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.

Photoconductivity, pH Sensitivity, Noise, and Channel Length Effects in Si Nanowire FET Sensors

NASA Astrophysics Data System (ADS)

Gasparyan, Ferdinand; Zadorozhnyi, Ihor; Khondkaryan, Hrant; Arakelyan, Armen; Vitusevich, Svetlana

2018-03-01

Silicon nanowire (NW) field-effect transistor (FET) sensors of various lengths were fabricated. Transport properties of Si NW FET sensors were investigated involving noise spectroscopy and current-voltage (I-V) characterization. The static I-V dependencies demonstrate the high quality of fabricated silicon FETs without leakage current. Transport and noise properties of NW FET structures were investigated under different light illumination conditions, as well as in sensor configuration in an aqueous solution with different pH values. Furthermore, we studied channel length effects on the photoconductivity, noise, and pH sensitivity. The magnitude of the channel current is approximately inversely proportional to the length of the current channel, and the pH sensitivity increases with the increase of channel length approaching the Nernst limit value of 59.5 mV/pH. We demonstrate that dominant 1/f-noise can be screened by the generation-recombination plateau at certain pH of the solution or external optical excitation. The characteristic frequency of the generation-recombination noise component decreases with increasing of illumination power. Moreover, it is shown that the measured value of the slope of 1/f-noise spectral density dependence on the current channel length is 2.7 which is close to the theoretically predicted value of 3.

A folate modified pH sensitive targeted polymeric micelle alleviated systemic toxicity of doxorubicin (DOX) in multi-drug resistant tumor bearing mice.

PubMed

Li, Xinru; Yang, Xiucong; Lin, Zhiqiang; Wang, Dan; Mei, Dong; He, Bing; Wang, Xiaoyou; Wang, Xueqing; Zhang, Qiang; Gao, Wei

2015-08-30

The purpose of this work was to demonstrate the advantages of a folate modified pH sensitive micelle system (HPPF) on reducing the systemic toxicity of antitumor drug doxorubicin (DOX) as well as increasing the antitumor efficacy on multi-drug resistant tumor. The micelle HPPF was fabricated by PHIS-PEG and Fol-PEG-PLA using dialysis method. Multi-drug resistant human breast-cancer cell (MCF-7Adr) was used to test the therapeutic effect of DOX loaded HPPF micelles (HPPF/DOX). Nude mice bearing MCF-7Adr tumor was used to evaluate the systemic toxicity of HPPF/DOX. The micelle HPPF was successfully prepared with good size uniformity and pH sensitivity. The in vitro experiments showed that HPPF significantly increased the intracellular level and cytotoxicity of DOX. The in vivo experiments demonstrated that HPPF had largely reduced the mortality and body weight loss, improved the animal status and decreased damages on heart and lung tissues comparing to free DOX. The HPPF/DOX could significantly increase the antitumor efficacy of DOX and largely alleviate the systemic side effects induced by high dose DOX in the treatment of multi-drug resistant tumor. Copyright © 2015 Elsevier B.V. All rights reserved.

Detection of ultraviolet radiation using tissue equivalent radiochromic gel materials

NASA Astrophysics Data System (ADS)

Bero, M. A.; Abukassem, I.

2009-05-01

Ferrous Xylenol-orange Gelatin gel (FXG) is known to be sensitive to ionising radiation such as γ and X-rays. The effect of ionising radiation is to produce an increase in the absorption over a wide region of the visible spectrum, which is proportional to the absorbed dose. This study demonstrates that FXG gel is sensitive to ultraviolet radiation and therefore it could functions as UV detector. Short exposure to UV radiation produces linear increase in absorption measured at 550nm, however high doses of UV cause the ion indicator colour to fad away in a manner proportional to the incident UV energy. Light absorbance increase at the rate of 1.1% per minute of irradiation was monitored. The exposure level at which the detector has linear response is comparable to the natural summer UV radiation. Evaluating the UV ability to pass through tissue equivalent gel materials shows that most of the UV gets absorbed in the first 5mm of the gel materials, which demonstrate the damaging effects of this radiation type on human skin and eyes. It was concluded that FXG gel dosimeter has the potential to offer a simple, passive ultraviolet radiation detector with sensitivity suitable to measure and visualises the natural sunlight UV exposure directly by watching the materials colour changes.

Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

NASA Astrophysics Data System (ADS)

Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

2017-12-01

Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care.

PubMed

Cherry, Simon R; Jones, Terry; Karp, Joel S; Qi, Jinyi; Moses, William W; Badawi, Ramsey D

2018-01-01

PET is widely considered the most sensitive technique available for noninvasively studying physiology, metabolism, and molecular pathways in the living human being. However, the utility of PET, being a photon-deficient modality, remains constrained by factors including low signal-to-noise ratio, long imaging times, and concerns about radiation dose. Two developments offer the potential to dramatically increase the effective sensitivity of PET. First by increasing the geometric coverage to encompass the entire body, sensitivity can be increased by a factor of about 40 for total-body imaging or a factor of about 4-5 for imaging a single organ such as the brain or heart. The world's first total-body PET/CT scanner is currently under construction to demonstrate how this step change in sensitivity affects the way PET is used both in clinical research and in patient care. Second, there is the future prospect of significant improvements in timing resolution that could lead to further effective sensitivity gains. When combined with total-body PET, this could produce overall sensitivity gains of more than 2 orders of magnitude compared with existing state-of-the-art systems. In this article, we discuss the benefits of increasing body coverage, describe our efforts to develop a first-generation total-body PET/CT scanner, discuss selected application areas for total-body PET, and project the impact of further improvements in time-of-flight PET. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

HEALTH SIGNIFICANCE OF PULMONARY FUNCTION TESTS

EPA Science Inventory

As the sensitivity and precision of functional tests improves, we become increasingly able to measure responses to pollutant exposures with little, if any, demonstrable health significance. Proper interpretation of such functional responses generally requires an ability to evalua...

Partially orthogonal resonators for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Chacon-Caldera, Jorge; Malzacher, Matthias; Schad, Lothar R.

2017-02-01

Resonators for signal reception in magnetic resonance are traditionally planar to restrict coil material and avoid coil losses. Here, we present a novel concept to model resonators partially in a plane with maximum sensitivity to the magnetic resonance signal and partially in an orthogonal plane with reduced signal sensitivity. Thus, properties of individual elements in coil arrays can be modified to optimize physical planar space and increase the sensitivity of the overall array. A particular case of the concept is implemented to decrease H-field destructive interferences in planar concentric in-phase arrays. An increase in signal to noise ratio of approximately 20% was achieved with two resonators placed over approximately the same planar area compared to common approaches at a target depth of 10 cm at 3 Tesla. Improved parallel imaging performance of this configuration is also demonstrated. The concept can be further used to increase coil density.

Voltage-sensitive rhodol with enhanced two-photon brightness.

PubMed

Kulkarni, Rishikesh U; Kramer, Daniel J; Pourmandi, Narges; Karbasi, Kaveh; Bateup, Helen S; Miller, Evan W

2017-03-14

We have designed, synthesized, and applied a rhodol-based chromophore to a molecular wire-based platform for voltage sensing to achieve fast, sensitive, and bright voltage sensing using two-photon (2P) illumination. Rhodol VoltageFluor-5 (RVF5) is a voltage-sensitive dye with improved 2P cross-section for use in thick tissue or brain samples. RVF5 features a dichlororhodol core with pyrrolidyl substitution at the nitrogen center. In mammalian cells under one-photon (1P) illumination, RVF5 demonstrates high voltage sensitivity (28% ΔF/F per 100 mV) and improved photostability relative to first-generation voltage sensors. This photostability enables multisite optical recordings from neurons lacking tuberous sclerosis complex 1, Tsc1, in a mouse model of genetic epilepsy. Using RVF5, we show that Tsc1 KO neurons exhibit increased activity relative to wild-type neurons and additionally show that the proportion of active neurons in the network increases with the loss of Tsc1. The high photostability and voltage sensitivity of RVF5 is recapitulated under 2P illumination. Finally, the ability to chemically tune the 2P absorption profile through the use of rhodol scaffolds affords the unique opportunity to image neuronal voltage changes in acutely prepared mouse brain slices using 2P illumination. Stimulation of the mouse hippocampus evoked spiking activity that was readily discerned with bath-applied RVF5, demonstrating the utility of RVF5 and molecular wire-based voltage sensors with 2P-optimized fluorophores for imaging voltage in intact brain tissue.

Direct questioning is more effective than patient-initiated report for the detection of sexually transmitted infections in a primary care HIV clinic in Western Kenya.

PubMed

Woo, Victoria Gah Hay; Cohen, Craig R; Bukusi, Elizabeth A; Huchko, Megan J

2013-02-01

In resource-limited settings, detection of sexually transmitted infections (STIs) often relies on self-reported symptoms to initiate management. We found self-report demonstrated poor sensitivity for STI detection. Adding clinician-initiated questions about symptoms improved detection rates. Vaginal examination further increased sensitivity. Including clinician-initiated screening in resource-limited settings would improve management of treatable STIs.

Sickle cell mice exhibit mechanical allodynia and enhanced responsiveness in light touch cutaneous mechanoreceptors

PubMed Central

2012-01-01

Background Sickle cell disease (SCD) is associated with both acute vaso-occlusive painful events as well as chronic pain syndromes, including heightened sensitivity to touch. We have previously shown that mice with severe SCD (HbSS mice; express 100% human sickle hemoglobin in red blood cells; RBCs) have sensitized nociceptors, which contribute to increased mechanical sensitivity. Yet, the hypersensitivity in these neural populations alone may not fully explain the mechanical allodynia phenotype in mouse and humans. Findings Using the Light Touch Behavioral Assay, we found HbSS mice exhibited increased responses to repeated application of both innocuous punctate and dynamic force compared to control HbAA mice (100% normal human hemoglobin). HbSS mice exhibited a 2-fold increase in percent response to a 0.7mN von Frey monofilament when compared to control HbAA mice. Moreover, HbSS mice exhibited a 1.7-fold increase in percent response to the dynamic light touch “puffed” cotton swab stimulus. We further investigated the mechanisms that drive this behavioral phenotype by focusing on the cutaneous sensory neurons that primarily transduce innocuous, light touch. Low threshold cutaneous afferents from HbSS mice exhibited sensitization to mechanical stimuli that manifested as an increase in the number of evoked action potentials to suprathreshold force. Rapidly adapting (RA) Aβ and Aδ D-hair fibers showed the greatest sensitization, each with a 75% increase in suprathreshold firing compared to controls. Slowly adapting (SA) Aβ afferents had a 25% increase in suprathreshold firing compared to HbAA controls. Conclusions These novel findings demonstrate mice with severe SCD exhibit mechanical allodynia to both punctate and dynamic light touch and suggest that this behavioral phenotype may be mediated in part by the sensitization of light touch cutaneous afferent fibers to suprathreshold force. These findings indicate that Aβ fibers can be sensitized to mechanical force and should potentially be examined for sensitization in other tissue injury and disease models. PMID:22963123

Glycine and GABAA Ultra-Sensitive Ethanol Receptors as Novel Tools for Alcohol and Brain Research

PubMed Central

Naito, Anna; Muchhala, Karan H.; Asatryan, Liana; Trudell, James R.; Homanics, Gregg E.; Perkins, Daya I.; Alkana, Ronald L.

2014-01-01

A critical obstacle to developing effective medications to prevent and/or treat alcohol use disorders is the lack of specific knowledge regarding the plethora of molecular targets and mechanisms underlying alcohol (ethanol) action in the brain. To identify the role of individual receptor subunits in ethanol-induced behaviors, we developed a novel class of ultra-sensitive ethanol receptors (USERs) that allow activation of a single receptor subunit population sensitized to extremely low ethanol concentrations. USERs were created by mutating as few as four residues in the extracellular loop 2 region of glycine receptors (GlyRs) or γ-aminobutyric acid type A receptors (GABAARs), which are implicated in causing many behavioral effects linked to ethanol abuse. USERs, expressed in Xenopus oocytes and tested using two-electrode voltage clamp, demonstrated an increase in ethanol sensitivity of 100-fold over wild-type receptors by significantly decreasing the threshold and increasing the magnitude of ethanol response, without altering general receptor properties including sensitivity to the neurosteroid, allopregnanolone. These profound changes in ethanol sensitivity were observed across multiple subunits of GlyRs and GABAARs. Collectively, our studies set the stage for using USER technology in genetically engineered animals as a unique tool to increase understanding of the neurobiological basis of the behavioral effects of ethanol. PMID:25245406

The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells.

PubMed

Dimopoulos, Nikolaos; Watson, Maria; Green, Charlotte; Hundal, Harinder S

2007-10-02

Peroxisome proliferator-activated receptor-delta (PPARdelta) activation enhances skeletal muscle fatty acid oxidation and improves whole body glucose homeostasis and insulin sensitivity. Recently, GW501516, a selective PPARdelta agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK-dependent mechanism that may contribute to the improved glucose tolerance. Here, we demonstrate that whilst GW501516 increases expression of PGC-1alpha and CPT-1 and stimulates fatty-acid oxidation in L6 myotubes, it fails to enhance insulin sensitivity, AMPK activity or glucose uptake and storage. Our findings exclude sarcolemmal glucose transport as a potential target for the therapeutic action of PPARdelta agonists in skeletal muscle.

Single input state, single–mode fiber–based polarization sensitive optical frequency domain imaging by eigenpolarization referencing

PubMed Central

Lippok, Norman; Villiger, Martin; Jun, Chang–Su; Bouma, Brett E.

2015-01-01

Fiber–based polarization sensitive OFDI is more challenging than free–space implementations. Using multiple input states, fiber–based systems provide sample birefringence information with the benefit of a flexible sample arm but come at the cost of increased system and acquisition complexity, and either reduce acquisition speed or require increased acquisition bandwidth. Here we show that with the calibration of a single polarization state, fiber–based configurations can approach the conceptual simplicity of traditional free–space configurations. We remotely control the polarization state of the light incident at the sample using the eigenpolarization states of a wave plate as a reference, and determine the Jones matrix of the output fiber. We demonstrate this method for polarization sensitive imaging of biological samples. PMID:25927775

Effect of fibril shape on adhesive properties

NASA Astrophysics Data System (ADS)

Soto, Daniel; Hill, Ginel; Parness, Aaron; Esparza, Noé; Cutkosky, Mark; Kenny, Tom

2010-08-01

Research into the gecko's adhesive system revealed a unique architecture for adhesives using tiny hairs. By using a stiff material (β-keratin) to create a highly structured adhesive, the gecko's system demonstrates properties not seen in traditional pressure-sensitive adhesives which use a soft, unstructured planar layer. In contrast to pressure sensitive adhesives, the gecko adhesive displays frictional adhesion, in which increased shear force allows it to withstand higher normal loads. Synthetic fibrillar adhesives have been fabricated but not all demonstrate this frictional adhesion property. Here we report the dual-axis force testing of single silicone rubber pillars from synthetic adhesive arrays. We find that the shape of the adhesive pillar dictates whether frictional adhesion or pressure-sensitive behavior is observed. This work suggests that both types of behavior can be achieved with structures much larger than gecko terminal structures. It also indicates that subtle differences in the shape of these pillars can significantly influence their properties.

Multi-modal approach using Raman spectroscopy and optical coherence tomography for the discrimination of colonic adenocarcinoma from normal colon

PubMed Central

Ashok, Praveen C.; Praveen, Bavishna B.; Bellini, Nicola; Riches, Andrew; Dholakia, Kishan; Herrington, C. Simon

2013-01-01

We report a multimodal optical approach using both Raman spectroscopy and optical coherence tomography (OCT) in tandem to discriminate between colonic adenocarcinoma and normal colon. Although both of these non-invasive techniques are capable of discriminating between normal and tumour tissues, they are unable individually to provide both the high specificity and high sensitivity required for disease diagnosis. We combine the chemical information derived from Raman spectroscopy with the texture parameters extracted from OCT images. The sensitivity obtained using Raman spectroscopy and OCT individually was 89% and 78% respectively and the specificity was 77% and 74% respectively. Combining the information derived using the two techniques increased both sensitivity and specificity to 94% demonstrating that combining complementary optical information enhances diagnostic accuracy. These data demonstrate that multimodal optical analysis has the potential to achieve accurate non-invasive cancer diagnosis. PMID:24156073

Insulin Sensitivity and Inflammation Mediate the Impact of Fitness on Cerebrovascular Health in Adolescents.

PubMed

Yau, Po Lai; Ross, Naima; Tirsi, Andrew; Arif, Arslan; Ozinci, Zeynep; Convit, Antonio

2017-06-01

To investigate in adolescents the relationships between retinal vessel diameter, physical fitness, insulin sensitivity, and systemic inflammation. We evaluated 157 adolescents, 112 with excessive weight and 45 lean, all without type 2 diabetes mellitus. All received detailed evaluations, including measurements of retinal vessel diameter, insulin sensitivity, levels of inflammation, and physical fitness. Overweight/obese adolescents had significantly narrower retinal arteriolar and wider venular diameters, significantly lower insulin sensitivity, and physical fitness. They also had decreased levels of anti-inflammatory and increased levels of proinflammatory markers as well as an overall higher inflammation balance score. Fitness was associated with larger retinal arteriolar and narrower venular diameters and these relationships were mediated by insulin sensitivity. We demonstrate that inflammation also mediates the relationship between fitness and retinal venular, but not arterial diameter; insulin sensitivity and inflammation balance score jointly mediate this relationship with little overlap in their effects. Increasing fitness and insulin sensitivity and reducing inflammation among adolescents carrying excess weight may improve microvascular integrity. Interventions to improve physical fitness and insulin function and reduce inflammation in adolescents, a group likely to benefit from such interventions, may reduce not only cardiovascular disease in middle age, but also improve cerebrovascular function later in life.

Gold nanoparticles: enhanced optical trapping and sensitivity coupled with significant heating.

PubMed

Seol, Yeonee; Carpenter, Amanda E; Perkins, Thomas T

2006-08-15

Gold nanoparticles appear to be superior handles in optical trapping assays. We demonstrate that relatively large gold particles (R(b)=50 nm) indeed yield a sixfold enhancement in trapping efficiency and detection sensitivity as compared to similar-sized polystyrene particles. However, optical absorption by gold at the most common trapping wavelength (1064 nm) induces dramatic heating (266 degrees C/W). We determined this heating by comparing trap stiffness from three different methods in conjunction with detailed modeling. Due to this heating, gold nanoparticles are not useful for temperature-sensitive optical-trapping experiments, but may serve as local molecular heaters. Also, such particles, with their increased detection sensitivity, make excellent probes for certain zero-force biophysical assays.

Relative Sensitivity of Photosynthesis and Respiration to Freeze-Thaw Stress in Herbaceous Species 1

PubMed Central

Steffen, Kenneth L.; Arora, Rajeev; Palta, Jiwan P.

1989-01-01

The relative effect of a freeze-thaw cycle on photosynthesis, respiration, and ion leakage of potato leaf tissue was examined in two potato species, Solanum acaule Bitt. and Solanum commersonii Dun. Photosynthesis was found to be much more sensitive to freezing stress than was respiration, and demonstrated more than a 60% inhibition before any impairment of respiratory function was observed. Photosynthesis showed a slight to moderate inhibition when only 5 to 10% of the total electrolytes had leaked from the tissue (reversible injury). This was in contrast to respiration which showed no impairment until temperatures at which about 50% ion leakage (irreversible injury) had occurred. The influence of freeze-thaw protocol was further examined in S. acaule and S. commersonii, in order to explore discrepancies in the literature as to the relative sensitivities of photosynthesis and respiration. As bath cooling rates increased from 1°C/hour to about 3 or 6°C/hour, there was a dramatic increase in the level of damage to all measured cellular functions. The initiation of ice formation in deeply supercooled tissue caused even greater damage. As the cooling rates used in stress treatments increased, the differential sensitivity between photosynthesis and respiration nearly disappeared. Examination of agriculturally relevant, climatological data from an 11 year period confirmed that air cooling rates in the freezing range do not exceed 2°C/hour. It was demonstrated, in the studies presented here, that simply increasing the actual cooling rate from 1.0 to 2.9°C/hour, in frozen tissue from paired leaflet halves, meant the difference between cell survival and cell death. Images Figure 4 Figure 5 PMID:16666712

Evidence for sensitized fatigue pathways in patients with chronic fatigue syndrome.

PubMed

Staud, Roland; Mokthech, Meriem; Price, Donald D; Robinson, Michael E

2015-04-01

Patients with chronic fatigue syndrome (CFS) frequently demonstrate intolerance to physical exertion that is often reported as increased and long-lasting fatigue. Because no specific metabolic alterations have been identified in CFS patients, we hypothesized that sensitized fatigue pathways become activated during exercise corresponding with increased fatigue. After exhausting handgrip exercise, muscle metabolites were trapped in the forearm tissues of 39 CFS patients and 29 normal control (NC) by sudden occlusion for up to 5 minutes. A nonocclusive condition of similar duration was used as control. Repeated fatigue and pain ratings were obtained before and after exercise. Mechanical and heat hyperalgesia were assessed by quantitative sensory testing. All subjects fulfilled the 1994 Fukuda Criteria for CFS. Normal control and CFS subjects exercised for 6.6 (2.4) and 7.0 (2.7) minutes (P > 0.05). Forearm occlusion lasted for 4.7 (1.3) and 4.9 (1.8) minutes in NC and CFS subjects, respectively (P > 0.05). Although fatigue ratings of CFS subjects increased from 4.8 (2.0) to 5.6 (2.1) visual analogue scale (VAS) units during forearm occlusion, they decreased from 5.0 (1.8) to 4.8 (2.0) VAS units during the control condition without occlusion (P = 0.04). A similar time course of fatigue ratings was observed in NC (P > 0.05), although their ratings were significantly lower than those of CFS subjects (P < 0.001). Quantitative sensory testing demonstrated heat and mechanical hyperalgesia in CFS subjects. Our findings provide indirect evidence for significant contributions of peripheral tissues to the increased exercise-related fatigue in CFS patients consistent with sensitization of fatigue pathways. Future interventions that reduce sensitization of fatigue pathways in CFS patients may be of therapeutic benefit.

Norepinephrine regulates hepatic innate immune system in leptin-deficient mice with nonalcoholic steatohepatitis.

PubMed

Li, Zhiping; Oben, Jude A; Yang, Shiqi; Lin, Huizhi; Stafford, Elizabeth A; Soloski, Mark J; Thomas, Steven A; Diehl, Anna Mae

2004-08-01

It is not known why natural killer T (NKT) cells, which modulate liver injury by regulating local cytokine production, are reduced in leptin-deficient ob/ob mice. NKT cells express adrenoceptors. Thus, we hypothesize that the low norepinephrine (NE) activity of ob/ob mice promotes depletion of liver NKT cells, thereby sensitizing ob/ob livers to lipopolysaccharide (LPS) toxicity. To evaluate this hypothesis, hepatic NKT cells were quantified in wild-type mice before and after treatment with NE inhibitors, and in dopamine beta-hydroxylase knockout mice (which cannot synthesize NE) and ob/ob mice before and after 4 weeks of NE supplementation. Decreasing NE activity consistently reduces liver NKT cells, while increasing NE has the opposite effect. Analysis of hepatic and thymic NKT cells in mice of different ages demonstrate an age-related accumulation of hepatic NKT cells in normal mice, while liver NKT cells become depleted after birth in ob/ob mice, which have increased apoptosis of hepatic NKT cells. NE treatment inhibits apoptosis and restores hepatic NKT cells. In ob/ob mice with reduced hepatic NKT cells, hepatic T and NKT cells produce excessive T helper (Th)-1 proinflammatory cytokines and the liver is sensitized to LPS toxicity. NE treatment decreases Th-1 cytokines, increases production of Th-2 cytokines, and reduces hepatotoxicity. Studies of CD1d-deficient mice, which lack the receptor required for NKT cell development, demonstrate that they are also unusually sensitive to LPS hepatotoxicity. In conclusion, low NE activity increases hepatic NKT cell apoptosis and depletes liver NKT cells, promoting proinflammatory polarization of hepatic cytokine production that sensitizes the liver to LPS toxicity. Copyright 2004 American Association for the Study of Liver Diseases

Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps

PubMed Central

2011-01-01

Background We and others have demonstrated previously that ghrelin receptor (GhrR) knock out (KO) mice fed a high fat diet (HFD) have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI-E) clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity. Results Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1st phase insulin secretion was still achieved, indicating that a healthy β-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd), and decreased hepatic glucose production (HGP). HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice. Conclusions These results indicate that improved glucose homeostasis of GhrR KO mice is characterized by robust improvements of glucose disposal in both normal and metabolically challenged states, relative to WT controls. GhrR KO mice have an intact 1st phase insulin response but require significantly less insulin for glucose disposal. Our experiments reveal that the insulin sensitivity of GhrR KO mice is due to both BW independent and dependent factors. We also provide several lines of evidence that a key feature of the GhrR KO mouse is maintenance of hepatic insulin sensitivity during metabolic challenge. PMID:21211044

Deficiency in endogenous modulation of prolonged heat pain in patients with Irritable Bowel Syndrome and Temporomandibular Disorder

PubMed Central

King, Christopher D.; Wong, Fong; Currie, Tom; Mauderli, Andre P.; Fillingim, Roger B.; Riley, Joseph L.

2013-01-01

Females with Irritable Bowel Syndrome (IBS) and Temporomandibular Disorder (TMD) are characterized by enhanced sensitivity to experimental pain. One possible explanation for this observation is deficiencies in pain modulation systems like Diffuse Noxious Inhibitory Control (DNIC). In a few studies that used brief stimuli, chronic pain patients demonstrate reduced DNIC. The purpose of this study was to compare sensitivity to prolonged heat pain and the efficacy of DNIC in controls to IBS and TMD patients. Heat pain (experimental stimulus; 44.0-49.0°C), which was applied to left palm, was continuously rated during three 30-second trials across three separate testing sessions under the following conditions: without a conditioning stimulus; during concurrent immersion of the right foot in a 23.0°C (control); and during noxious cold immersion in a (DNIC; 8.0-16.0°C) water bath. Compared to controls, IBS and TMD patients reported increased sensitivity to heat pain and failed to demonstrate pain inhibition due to DNIC. Controls showed a significant reduction in pain during the DNIC session. These findings support the idea that chronic pain patients are not only more pain sensitive and demonstrate reduced pain inhibition by pain, possibly because of dysfunction of endogenous pain inhibition systems. PMID:19278784

IMRT QA: Selecting gamma criteria based on error detection sensitivity.

PubMed

Steers, Jennifer M; Fraass, Benedick A

2016-04-01

The gamma comparison is widely used to evaluate the agreement between measurements and treatment planning system calculations in patient-specific intensity modulated radiation therapy (IMRT) quality assurance (QA). However, recent publications have raised concerns about the lack of sensitivity when employing commonly used gamma criteria. Understanding the actual sensitivity of a wide range of different gamma criteria may allow the definition of more meaningful gamma criteria and tolerance limits in IMRT QA. We present a method that allows the quantitative determination of gamma criteria sensitivity to induced errors which can be applied to any unique combination of device, delivery technique, and software utilized in a specific clinic. A total of 21 DMLC IMRT QA measurements (ArcCHECK®, Sun Nuclear) were compared to QA plan calculations with induced errors. Three scenarios were studied: MU errors, multi-leaf collimator (MLC) errors, and the sensitivity of the gamma comparison to changes in penumbra width. Gamma comparisons were performed between measurements and error-induced calculations using a wide range of gamma criteria, resulting in a total of over 20 000 gamma comparisons. Gamma passing rates for each error class and case were graphed against error magnitude to create error curves in order to represent the range of missed errors in routine IMRT QA using 36 different gamma criteria. This study demonstrates that systematic errors and case-specific errors can be detected by the error curve analysis. Depending on the location of the error curve peak (e.g., not centered about zero), 3%/3 mm threshold = 10% at 90% pixels passing may miss errors as large as 15% MU errors and ±1 cm random MLC errors for some cases. As the dose threshold parameter was increased for a given %Diff/distance-to-agreement (DTA) setting, error sensitivity was increased by up to a factor of two for select cases. This increased sensitivity with increasing dose threshold was consistent across all studied combinations of %Diff/DTA. Criteria such as 2%/3 mm and 3%/2 mm with a 50% threshold at 90% pixels passing are shown to be more appropriately sensitive without being overly strict. However, a broadening of the penumbra by as much as 5 mm in the beam configuration was difficult to detect with commonly used criteria, as well as with the previously mentioned criteria utilizing a threshold of 50%. We have introduced the error curve method, an analysis technique which allows the quantitative determination of gamma criteria sensitivity to induced errors. The application of the error curve method using DMLC IMRT plans measured on the ArcCHECK® device demonstrated that large errors can potentially be missed in IMRT QA with commonly used gamma criteria (e.g., 3%/3 mm, threshold = 10%, 90% pixels passing). Additionally, increasing the dose threshold value can offer dramatic increases in error sensitivity. This approach may allow the selection of more meaningful gamma criteria for IMRT QA and is straightforward to apply to other combinations of devices and treatment techniques.

Mechanism and Characteristics of Humidity Sensing with Polyvinyl Alcohol-Coated Fiber Surface Plasmon Resonance Sensor.

PubMed

Shao, Yu; Wang, Ying; Cao, Shaoqing; Huang, Yijian; Zhang, Longfei; Zhang, Feng; Liao, Changrui; Wang, Yiping

2018-06-25

A surface plasmon resonance (SPR) sensor based on a side-polished single mode fiber coated with polyvinyl alcohol (PVA) is demonstrated for relative humidity (RH) sensing. The SPR sensor exhibits a resonant dip in the transmission spectrum in ambient air after PVA film coating, and the resonant wavelength shifts to longer wavelengths as the thickness of the PVA film increases. When RH changes, the resonant dip of the sensor with different film-thicknesses exhibits interesting characteristics for optical spectrum evolution. For sensors with initial wavelengths between 550 nm and 750 nm, the resonant dip shifts to longer wavelengths with increasing RH. The averaged sensitivity increases firstly and then drops, and shows a maximal sensitivity of 1.01 nm/RH%. Once the initial wavelength of the SPR sensor exceeds 850 nm, an inflection point of the resonant wavelength shift can be observed with RH increasing, and the resonant dip shifts to shorter wavelengths for RH values exceeding this point, and sensitivity as high as −4.97 nm/RH% can be obtained in the experiment. The sensor is expected to have potential applications in highly sensitive and cost effective humidity sensing.

The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition

PubMed Central

2012-01-01

Background It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. Mcl-1 is a critical survival protein in a variety of cell lineages and is critically regulated via ubiquitination. Methods The Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon adenocarcinomas were evaluated via immunohistochemistry. Interaction between USP9X and Mcl-1 was demonstrated by immunoprecipitation-western blotting. The protein expression profiles of Mcl-1, Bcl-xL and USP9X in multiple cancer cell lines were determined by western blotting. Annexin-V staining and cleaved PARP western blotting were used to assay for apoptosis. The cellular toxicities after various treatments were measured via the XTT assay. Results In our current analysis of colon and lung cancer samples, we demonstrate that Mcl-1 and Bcl-xL are overexpressed and also co-exist in many tumors and that the expression levels of both genes correlate with the clinical staging. The downregulation of Mcl-1 or Bcl-xL via RNAi was found to increase the sensitivity of the tumor cells to chemotherapy. Furthermore, our analyses revealed that USP9X expression correlates with that of Mcl-1 in human cancer tissue samples. We additionally found that the USP9X inhibitor WP1130 promotes Mcl-1 degradation and increases tumor cell sensitivity to chemotherapies. Moreover, the combination of WP1130 and ABT-737, a well-documented Bcl-xL inhibitor, demonstrated a chemotherapeutic synergy and promoted apoptosis in different tumor cells. Conclusion Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors. PMID:23171055

P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells.

PubMed

Varshney, Pallavi; Dey, Chinmoy Sankar

2016-07-05

P21-activated kinases (PAKs) are recently reported as important players of insulin signaling and glucose homeostasis in tissues like muscle, pancreas and liver. However, their role in neuronal insulin signaling is still unknown. Present study reports the involvement of PAK2 in neuronal insulin signaling, glucose uptake and insulin resistance. Irrespective of insulin sensitivity, insulin stimulation decreased PAK2 activity. PAK2 downregulation displayed marked enhancement of GLUT4 translocation with increase in glucose uptake whereas PAK2 over-expression showed its reduction. Treatment with Akti-1/2 and wortmannin suggested that Akt and PI3K are mediators of insulin effect on PAK2 and glucose uptake. Rac1 inhibition demonstrated decreased PAK2 activity while inhibition of PP2A resulted in increased PAK2 activity, with corresponding changes in glucose uptake. Taken together, present study demonstrates an inhibitory role of insulin signaling (via PI3K-Akt) and PP2A on PAK2 activity and establishes PAK2 as a Rac1-dependent negative regulator of neuronal glucose uptake and insulin sensitivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sensitivity enhancement of fiber loop cavity ring-down pressure sensor.

PubMed

Jiang, Yajun; Yang, Dexing; Tang, Daqing; Zhao, Jianlin

2009-11-10

We present a theoretical and experimental study on sensitivity enhancement of a fiber-loop cavity ring-down pressure sensor. The cladding of the sensing fiber is etched in hydrofluoric acid solution to enhance its sensitivity. The experimental results demonstrate that the pressure applied on the sensing fiber is linearly proportional to the difference between the reciprocals of the ring-down time with and without pressure, and the relative sensitivity exponentially increases with decreasing the cladding diameter. When the sensing fiber is etched to 41.15 microm, its sensitivity is about 36 times that of nonetched fiber in the range of 0 to 32.5 MPa. The measured relative standard deviation of the ring-down time is about 0.15% and, correspondingly, the least detectable loss is about 0.00069 dB.

Operant conditioning of enhanced pain sensitivity by heat-pain titration.

PubMed

Becker, Susanne; Kleinböhl, Dieter; Klossika, Iris; Hölzl, Rupert

2008-11-15

Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain. Most experimental studies have investigated the operant modulation of verbal pain reports with extrinsic reinforcement, such as verbal reinforcement. Whether this reflects actual changes in the subjective experience of the nociceptive stimulus remained unclear. This study replicates and extends our previous demonstration that enhanced pain sensitivity to prolonged heat-pain stimulation could be learned in healthy participants through intrinsic reinforcement (contingent changes in nociceptive input) independent of verbal pain reports. In addition, we examine whether different magnitudes of reinforcement differentially enhance pain sensitivity using an operant heat-pain titration paradigm. It is based on the previously developed non-verbal behavioral discrimination task for the assessment of sensitization, which uses discriminative down- or up-regulation of stimulus temperatures in response to changes in subjective intensity. In operant heat-pain titration, this discriminative behavior and not verbal pain report was contingently reinforced or punished by acute decreases or increases in heat-pain intensity. The magnitude of reinforcement was varied between three groups: low (N1=13), medium (N2=11) and high reinforcement (N3=12). Continuous reinforcement was applied to acquire and train the operant behavior, followed by partial reinforcement to analyze the underlying learning mechanisms. Results demonstrated that sensitization to prolonged heat-pain stimulation was enhanced by operant learning within 1h. The extent of sensitization was directly dependent on the received magnitude of reinforcement. Thus, operant learning mechanisms based on intrinsic reinforcement may provide an explanation for the gradual development of sustained hypersensitivity during pain that is becoming chronic.

Controls on the early Holocene collapse of the Bothnian Sea Ice Stream

NASA Astrophysics Data System (ADS)

Clason, Caroline C.; Greenwood, Sarah L.; Selmes, Nick; Lea, James M.; Jamieson, Stewart S. R.; Nick, Faezeh M.; Holmlund, Per

2016-12-01

New high-resolution multibeam data in the Gulf of Bothnia reveal for the first time the subglacial environment of a Bothnian Sea Ice Stream. The geomorphological record suggests that increased meltwater production may have been important in driving rapid retreat of Bothnian Sea Ice during deglaciation. Here we apply a well-established, one-dimensional flow line model to simulate ice flow through the Gulf of Bothnia and investigate controls on retreat of the ice stream during the post-Younger Dryas deglaciation of the Fennoscandian Ice Sheet. The relative influence of atmospheric and marine forcings are investigated, with the modeled ice stream exhibiting much greater sensitivity to surface melting, implemented through surface mass balance and hydrofracture-induced calving, than to submarine melting or relative sea level change. Such sensitivity is supported by the presence of extensive meltwater features in the geomorphological record. The modeled ice stream does not demonstrate significant sensitivity to changes in prescribed ice stream width or overall bed slope, but local variations in basal topography and ice stream width result in nonlinear retreat of the grounding line, notably demonstrating points of short-lived retreat slowdown on reverse bed slopes. Retreat of the ice stream was most likely governed by increased ice surface meltwater production, with the modeled retreat rate less sensitive to marine forcings despite the marine setting.

Patients with chronic tension-type headache demonstrate increased mechano-sensitivity of the supra-orbital nerve.

PubMed

Fernández-de-Las-Peñas, César; Coppieters, Michel W; Cuadrado, María Luz; Pareja, Juan A

2008-04-01

This study aimed to establish whether increased sensitivity to mechanical stimuli is present in neural tissues in chronic tension-type headache (CTTH). Muscle hyperalgesia is a common finding in CTTH. No previous studies have investigated the sensitivity of peripheral nerves in patients with CTTH. A blinded controlled study. Pressure pain thresholds (PPT) and pain intensity following palpation of the supra-orbital nerve (V1) were compared between 20 patients with CTTH and 20 healthy matched subjects. A pressure algometer and numerical pain rate scale were used to quantify PPT and pain to palpation. A headache diary was kept for 4 weeks to substantiate the diagnosis and record the pain history. The analysis of variance demonstrated significantly lower PPT for patients (0.86+/-0.13 kg/cm2) than controls (1.50+/-0.19 kg/cm2) (P<.001). Pain to palpation was also higher for patients (2.73+/-1.58) than controls (0.15+/-0.28) (P<.001). Within the CTTH group, intensity, frequency, and duration of the headaches were negatively correlated with PPT (rsor=0.72; P<.001). These findings reveal that mechanical hypersensitivity is not limited to muscles but also occurs in cranial nerves, and that the level of sensitization, either due to peripheral or central processes, is related to the severity of the primary headache.

Cell death sensitization of leukemia cells by opioid receptor activation

PubMed Central

Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A.; Debatin, Klaus-Michael; Miltner, Erich

2013-01-01

Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. PMID:23633472

Vitamin D, Race, and Experimental Pain Sensitivity in Older Adults with Knee Osteoarthritis

PubMed Central

Glover, T.L.; Goodin, B.R.; Horgas, A.L.; Kindler, L.L.; King, C.D.; Sibille, K.T.; Peloquin, C.A.; Riley, J.L.; Staud, R.; Bradley, L.A.; Fillingim, R.B.

2012-01-01

Objective Low levels of serum circulating 25-hydroxyvitamin D have been correlated with many health conditions, including chronic pain. Recent clinical practice guidelines define vitamin D levels < 20 ng/mL as deficient and values of 21–29 ng/mL as insufficient. Vitamin D insufficiency, including the most severe levels of deficiency, is more prevalent in black Americans. Ethnic and race group differences have been reported in both clinical and experimental pain, with black Americans reporting increased pain. The purpose of this study was to examine whether variation in vitamin D levels contribute to race differences in knee osteoarthritic pain. Methods The sample consisted of 94 participants (75% female), including 45 blacks and 49 whites with symptomatic knee osteoarthritis. Average age was 55.8 years (range 45–71 years). Participants completed a questionnaire on knee osteoarthritic symptoms and underwent quantitative sensory testing, including measures of heat and mechanical pain sensitivity. Results Blacks had significantly lower levels of vitamin D compared to whites, demonstrated greater clinical pain, and showed greater sensitivity to mechanical and heat pain. Low levels of vitamin D predicted increased experimental pain sensitivity, but did not predict self-reported clinical pain. Group differences in vitamin D significantly predicted group differences in heat pain and pressure pain thresholds on the index knee and ipsilateral forearm. Conclusion These data demonstrate race differences in experimental pain are mediated by differences in vitamin D level. Vitamin D deficiency may be a risk factor for increased knee osteoarthritic pain in black Americans. PMID:23135697

The association of noise sensitivity with music listening, training, and aptitude.

PubMed

Kliuchko, Marina; Heinonen-Guzejev, Marja; Monacis, Lucia; Gold, Benjamin P; Heikkilä, Kauko V; Spinosa, Vittoria; Tervaniemi, Mari; Brattico, Elvira

2015-01-01

After intensive, long-term musical training, the auditory system of a musician is specifically tuned to perceive musical sounds. We wished to find out whether a musician's auditory system also develops increased sensitivity to any sound of everyday life, experiencing them as noise. For this purpose, an online survey, including questionnaires on noise sensitivity, musical background, and listening tests for assessing musical aptitude, was administered to 197 participants in Finland and Italy. Subjective noise sensitivity (assessed with the Weinstein's Noise Sensitivity Scale) was analyzed for associations with musicianship, musical aptitude, weekly time spent listening to music, and the importance of music in each person's life (or music importance). Subjects were divided into three groups according to their musical expertise: Nonmusicians (N = 103), amateur musicians (N = 44), and professional musicians (N = 50). The results showed that noise sensitivity did not depend on musical expertise or performance on musicality tests or the amount of active (attentive) listening to music. In contrast, it was associated with daily passive listening to music, so that individuals with higher noise sensitivity spent less time in passive (background) listening to music than those with lower sensitivity to noise. Furthermore, noise-sensitive respondents rated music as less important in their life than did individuals with lower sensitivity to noise. The results demonstrate that the special sensitivity of the auditory system derived from musical training does not lead to increased irritability from unwanted sounds. However, the disposition to tolerate contingent musical backgrounds in everyday life depends on the individual's noise sensitivity.

Chemical cues from fish heighten visual sensitivity in larval crabs through changes in photoreceptor structure and function.

PubMed

Charpentier, Corie L; Cohen, Jonathan H

2015-11-01

Several predator avoidance strategies in zooplankton rely on the use of light to control vertical position in the water column. Although light is the primary cue for such photobehavior, predator chemical cues or kairomones increase swimming responses to light. We currently lack a mechanistic understanding for how zooplankton integrate visual and chemical cues to mediate phenotypic plasticity in defensive photobehavior. In marine systems, kairomones are thought to be amino sugar degradation products of fish body mucus. Here, we demonstrate that increasing concentrations of fish kairomones heightened sensitivity of light-mediated swimming behavior for two larval crab species (Rhithropanopeus harrisii and Hemigrapsus sanguineus). Consistent with these behavioral results, we report increased visual sensitivity at the retinal level in larval crab eyes directly following acute (1-3 h) kairomone exposure, as evidenced electrophysiologically from V-log I curves and morphologically from wider, shorter rhabdoms. The observed increases in visual sensitivity do not correspond with a decline in temporal resolution, because latency in electrophysiological responses actually increased after kairomone exposure. Collectively, these data suggest that phenotypic plasticity in larval crab photobehavior is achieved, at least in part, through rapid changes in photoreceptor structure and function. © 2015. Published by The Company of Biologists Ltd.

Kalirin-7 Mediates Cocaine-Induced AMPA Receptor and Spine Plasticity, Enabling Incentive Sensitization

PubMed Central

Wang, Xiaoting; Cahill, Michael E.; Werner, Craig T.; Christoffel, Daniel J.; Golden, Sam A.; Xie, Zhong; Loweth, Jessica A.; Marinelli, Michela; Russo, Scott J.; Penzes, Peter

2013-01-01

It is well established that behavioral sensitization to cocaine is accompanied by increased spine density and AMPA receptor (AMPAR) transmission in the nucleus accumbens (NAc), but two major questions remain unanswered. Are these adaptations mechanistically coupled? And, given that they can be dissociated from locomotor sensitization, what is their functional significance? We tested the hypothesis that the guanine-nucleotide exchange factor Kalirin-7 (Kal-7) couples cocaine-induced AMPAR and spine upregulation and that these adaptations underlie sensitization of cocaine's incentive-motivational properties—the properties that make it “wanted.” Rats received eight daily injections of saline or cocaine. On withdrawal day 14, we found that Kal-7 levels and activation of its downstream effectors Rac-1 and PAK were increased in the NAc of cocaine-sensitized rats. Furthermore, AMPAR surface expression and spine density were increased, as expected. To determine whether these changes require Kal-7, a lentiviral vector expressing Kal-7 shRNA was injected into the NAc core before cocaine exposure. Knocking down Kal-7 abolished the AMPAR and spine upregulation normally seen during cocaine withdrawal. Despite the absence of these adaptations, rats with reduced Kal-7 levels developed locomotor sensitization. However, incentive sensitization, which was assessed by how rapidly rats learned to self-administer a threshold dose of cocaine, was severely impaired. These results identify a signaling pathway coordinating AMPAR and spine upregulation during cocaine withdrawal, demonstrate that locomotor and incentive sensitization involve divergent mechanisms, and link enhanced excitatory transmission in the NAc to incentive sensitization. PMID:23825406

A sensitive assay using a native protein substrate for screening HIV-1 maturation inhibitors targeting the protease cleavage site between the matrix and capsid.

PubMed

Lee, Sook-Kyung; Cheng, Nancy; Hull-Ryde, Emily; Potempa, Marc; Schiffer, Celia A; Janzen, William; Swanstrom, Ronald

2013-07-23

The matrix/capsid processing site in the HIV-1 Gag precursor is likely the most sensitive target to inhibit HIV-1 replication. We have previously shown that modest incomplete processing at the site leads to a complete loss of virion infectivity. In the study presented here, a sensitive assay based on fluorescence polarization that can monitor cleavage at the MA/CA site in the context of the folded protein substrate is described. The substrate, an MA/CA fusion protein, was labeled with the fluorescein-based FlAsH (fluorescein arsenical hairpin) reagent that binds to a tetracysteine motif (CCGPCC) that was introduced within the N-terminal domain of CA. By limiting the size of CA and increasing the size of MA (with an N-terminal GST fusion), we were able to measure significant differences in polarization values as a function of HIV-1 protease cleavage. The sensitivity of the assay was tested in the presence of increasing amounts of an HIV-1 protease inhibitor, which resulted in a gradual decrease in the fluorescence polarization values demonstrating that the assay is sensitive in discerning changes in protease processing. The high-throughput screening assay validation in 384-well plates showed that the assay is reproducible and robust with an average Z' value of 0.79 and average coefficient of variation values of <3%. The robustness and reproducibility of the assay were further validated using the LOPAC(1280) compound library, demonstrating that the assay provides a sensitive high-throughput screening platform that can be used with large compound libraries for identifying novel maturation inhibitors targeting the MA/CA site of the HIV-1 Gag polyprotein.

Post-trial dopaminergic modulation of conditioned catalepsy: A single apomorphine induced increase/decrease in dopaminergic activation immediately following a conditioned catalepsy response can reverse/enhance a haloperidol conditioned and sensitized catalepsy response.

PubMed

Oliveira, Lucas Rangel; Dias, Flávia Regina Cruz; Santos, Breno Garone; Silva, Jade Leal Loureiro; Carey, Robert J; Carrera, Marinete Pinheiro

2016-09-15

Haloperidol can induce catalepsy and this drug effect can be conditioned as well as sensitized to contextual cues. We used a paired/unpaired Pavlovian conditioning protocol to establish haloperidol catalepsy conditioned and sensitized responses. Groups of rats were given 10 daily catalepsy tests following administration of vehicle (n=24) or haloperidol (1.0mg/kg) either paired (n=18) or unpaired (n=18) to testing. Subsequently, testing for conditioning was conducted and conditioning and sensitization of catalepsy were observed selectively in the paired group. Immediately following a second test for catalepsy conditioning, the groups were subdivided into 4 vehicle groups, 3 unpaired haloperidol groups and 3 paired haloperidol groups and were given one of three post-trial treatments (vehicle, 0.05mg/kg or 2.0mg/kg apomorphine). One day later the conditioned catalepsy test 3 was carried out and on the next day, a haloperidol challenge test was performed. The post-trial apomorphine treatments had major effects on the paired groups upon both conditioning and the haloperidol challenge test. The low dose apomorphine post-trial treatment enhanced both the conditioned and the haloperidol sensitized catalepsy responses. The high dose apomorphine post-trial treatment eliminated conditioned catalepsy and eliminated the initial acute catalepsy response to haloperidol that was induced in the vehicle control groups. These results demonstrate the sensitivity of conditioned drug cues to modification by increases/decreases in activity of the dopamine system in the immediate post-trial interval after a conditioning trial. This demonstration that post-trial dopaminergic drug treatments can modify conditioned drug behavior has broad implications for conditioned drug effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Paired emitter-detector diode detection with dual wavelength monitoring for enhanced sensitivity to transition metals in ion chromatography with post-column reaction.

PubMed

O' Toole, Martina; Barron, Leon; Shepherd, Roderick; Paull, Brett; Nesterenko, Pavel; Diamond, Dermot

2009-01-01

The combination of post-column derivatisation and visible detection are regularly employed in ion chromatography (IC) to detect poorly absorbing species. Although this mode is often highly sensitive, one disadvantage is the increase in repeating baseline artifacts associated with out-of-sync pumping systems. The work presented here will demonstrate the use of a second generation design paired emitter-detector diode (PEDD-II) detection mode offering enhanced sensitivity to transition metals in IC by markedly reducing this problem and also by improving signal noise. First generation designs demonstrated the use of a single integrated PEDD detector cell as a simple, small (15 x 5 mm), highly sensitive, low cost photometric detector for the detection of metals in IC. The basic principle of this detection mode lies in the employment of two linear light emitting diodes (LEDs), one operating in normal mode as a light source and the other in reverse bias serving as a light detector. The second generation PEDD-II design showed increased sensitivity for Mn(II)- and Co(II)-2-(pyridylazo)resorcinol (PAR) complexes as a result of two simultaneously acquiring detection cells--one analytical PEDD cell and one reference PEDD cell. Therefore, the PEDD-II employs two wavelengths whereby one monitors the analyte reaction product and the second monitors a wavelength close to the isosbestic point. The optimum LED wavelength to be used for the analytical cell was investigated to maximise peak response. The fabrication process for both the analytical and reference PEDD cells was validated by determining the reproducibility of detectors within a batch. The reproducibility and sensitivity of the PEDD-II detector was then investigated using signals obtained from both intra- and inter-day chromatograms.

Alcohol-induced S-adenosylhomocysteine accumulation in the liver sensitizes to TNF hepatotoxicity: possible involvement of mitochondrial S-adenosylmethionine transport.

PubMed

Song, Zhenyuan; Zhou, Zhanxiang; Song, Ming; Uriarte, Silvia; Chen, Theresa; Deaciuc, Ion; McClain, Craig J

2007-08-01

Hepatocytes are resistant to tumor necrosis factor-alpha- (TNF) induced killing/apoptosis under normal circumstances, but primary hepatocytes from rats chronically fed alcohol have increased TNF cytotoxicity. Therefore, there must be mechanism(s) by which alcohol exposure "sensitizes" to TNF hepatotoxicity. Abnormal metabolism of methionine and S-adenosylmethionine (SAM) are well-documented acquired metabolic abnormalities in ALD. S-adenosylhomocysteine (SAH) is the product of SAM in hepatic transmethylation reactions, and SAH hydrolase (SAHH) is the only enzyme to metabolize SAH to homocysteine and adenosine. Our previous studies demonstrated that chronic intracellular accumulation of SAH sensitized hepatocytes to TNF cytotoxicity in vitro. In the current study, we extended our previous observations by further characterizing the effects of chronic alcohol intake on mitochondrial SAM levels in liver and examining its possible involvement in SAH sensitization to TNF hepatotoxicity. Chronic alcohol consumption in mice not only increased cytosolic SAH levels, but also decreased mitochondrial SAM concentration, leading to decreased mitochondrial SAM to SAH ratio. Moreover, accumulation of hepatic SAH induced by administration of 3-deaza-adenosine (DZA-a potent inhibitor of SAHH) enhanced lipopolysaccharide (LPS)/TNF hepatotoxicity in mice in vivo. Inhibition of SAHH by DZA resulted not only in accumulation of cytoplasmic SAH, but also in depletion of the mitochondrial SAM pool. Further studies using mitochondrial SAM transporter inhibitors showed that inhibition of SAM transport into mitochondria sensitized HepG2 cells to TNF cytotoxicity. In conclusion, our results demonstrate that depletion of the mitochondrial SAM pool by SAH, which is elevated during chronic alcohol consumption, plays a critical role in SAH induced sensitization to TNF hepatotoxicity.

Nanoamplifiers synthesized from gadolinium and gold nanocomposites for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Tian, Xiumei; Shao, Yuanzhi; He, Haoqiang; Liu, Huan; Shen, Yingying; Huang, Wenlin; Li, Li

2013-03-01

We have synthesized an efficient and highly sensitive nanoamplifier composed of gadolinium-doped silica nanoparticles and gold nanoparticles (AuNPs). Magnetic resonance imaging (MRI) in vitro and in vivo assays revealed enhancement of signal sensitivity, which may be explained by electron transfer between water and gadolinium-doped nanoparticles, apparent in the presence of gold. In vitro and in vivo evaluation demonstrated nanoamplifier incurred minimal cytotoxicity and immunotoxicity, increased stability, and gradual excretion patterns. Tumor targeted properties were preliminarily determined when the nanoamplifier was injected into mouse models of colon cancer liver metastasis. Furthermore, although AuNPs departed from the nanoamplifiers in specific mice tissues, optical and magnetic resonance imaging was efficient, especially in metastatic tumors. These assays validate our nanoamplifier as an effective MRI signal enhancer with sensitive cancer diagnosis potential.We have synthesized an efficient and highly sensitive nanoamplifier composed of gadolinium-doped silica nanoparticles and gold nanoparticles (AuNPs). Magnetic resonance imaging (MRI) in vitro and in vivo assays revealed enhancement of signal sensitivity, which may be explained by electron transfer between water and gadolinium-doped nanoparticles, apparent in the presence of gold. In vitro and in vivo evaluation demonstrated nanoamplifier incurred minimal cytotoxicity and immunotoxicity, increased stability, and gradual excretion patterns. Tumor targeted properties were preliminarily determined when the nanoamplifier was injected into mouse models of colon cancer liver metastasis. Furthermore, although AuNPs departed from the nanoamplifiers in specific mice tissues, optical and magnetic resonance imaging was efficient, especially in metastatic tumors. These assays validate our nanoamplifier as an effective MRI signal enhancer with sensitive cancer diagnosis potential. Electronic supplementary information (ESI) available: Protocols for the characterization, immunotoxicity and pharmacokinetics analyses. Additional supporting figures. See DOI: 10.1039/c3nr00170a

Study of polarization properties of fiber-optics probes with use of a binary phase plate.

PubMed

Alferov, S V; Khonina, S N; Karpeev, S V

2014-04-01

We conduct a theoretical and experimental study of the distribution of the electric field components in the sharp focal domain when rotating a zone plate with a π-phase jump placed in the focused beam. Comparing the theoretical and experimental results for several kinds of near-field probes, an analysis of the polarization sensitivity of different types of metal-coated aperture probes is conducted. It is demonstrated that with increasing diameter of the non-metal-coated tip part there occurs an essential redistribution of sensitivity in favor of the transverse electric field components and an increase of the probe's energy throughput.

PCR/LDR/universal array platforms for the diagnosis of infectious disease.

PubMed

Pingle, Maneesh; Rundell, Mark; Das, Sanchita; Golightly, Linnie M; Barany, Francis

2010-01-01

Infectious diseases account for between 14 and 17 million deaths worldwide each year. Accurate and rapid diagnosis of bacterial, fungal, viral, and parasitic infections is therefore essential to reduce the morbidity and mortality associated with these diseases. Classical microbiological and serological methods have long served as the gold standard for diagnosis but are increasingly being replaced by molecular diagnostic methods that demonstrate increased sensitivity and specificity and provide an identification of the etiologic agent in a shorter period of time. PCR/LDR coupled with universal array detection provides a highly sensitive and specific platform for the detection and identification of bacterial and viral infections.

PCR/LDR/Universal Array Platforms for the Diagnosis of Infectious Disease

PubMed Central

Pingle, Maneesh; Rundell, Mark; Das, Sanchita; Golightly, Linnie M.; Barany, Francis

2015-01-01

Infectious diseases account for between 14 and 17 million deaths worldwide each year. Accurate and rapid diagnosis of bacterial, fungal, viral, and parasitic infections is therefore essential to reduce the morbidity and mortality associated with these diseases. Classical microbiological and serological methods have long served as the gold standard for diagnosis but are increasingly being replaced by molecular diagnostic methods that demonstrate increased sensitivity and specificity and provide an identification of the etiologic agent in a shorter period of time. PCR/LDR coupled with universal array detection provides a highly sensitive and specific platform for the detection and identification of bacterial and viral infections. PMID:20217576

Bioengineering bacteriophages to enhance the sensitivity of phage amplification-based paper fluidic detection of bacteria.

PubMed

Alcaine, S D; Law, K; Ho, S; Kinchla, A J; Sela, D A; Nugen, S R

2016-08-15

Bacteriophage (phage) amplification is an attractive method for the detection of bacteria due to a narrow phage-host specificity, short amplification times, and the phages' ability to differentiate between viable and non-viable bacterial cells. The next step in phage-based bacteria detection is leveraging bioengineered phages to create low-cost, rapid, and easy-to-use detection platforms such as lateral flow assays. Our work establishes the proof-of-concept for the use of bioengineered T7 phage strains to increase the sensitivity of phage amplification-based lateral flow assays. We have demonstrated a greater than 10-fold increase in sensitivity using a phage-based protein reporter, maltose-binding protein, over the detection of replicated T7 phage viron itself, and a greater then 100-fold increase in sensitivity using a phage-based enzymatic reporter, alkaline phosphatase. This increase in sensitivity enabled us to detect 10(3)CFU/mL of Escherichia coli in broth after 7h, and by adding a filter concentration step, the ability to detect a regulatory relevant E. coli concentration of 100CFU/100mL in inoculated river water after 9h, where the current standard requires days for results. The combination of the paper fluidic format with phage-based detection provides a platform for the development of novel diagnostics that are sensitive, rapid, and easy to use. Copyright © 2016 Elsevier B.V. All rights reserved.

Sensitive and selective determination of fluvoxamine maleate using a sensitive chemiluminescence system based on the alkaline permanganate-Rhodamine B-gold nanoparticles reaction.

PubMed

Hassanzadeh, Javad; Amjadi, Mohammad

2015-06-01

A high-yield chemiluminescence (CL) system based on the alkaline permanganate-Rhodamine B reaction was developed for the sensitive determination of fluvoxamine maleate (Flu). Rhodamine B is oxidized by alkaline KMnO4 and a weak CL emission is produced. It was demonstrated that gold nanoparticles greatly enhance this CL emission due to their interaction with Rhodamine B molecules. It is also observed that sodium dodecyl sulfate, an anionic surfactant, can strongly increase this enhancement. In addition, it was demonstrated that a notable decrease in the CL intensity is observed in the presence of Flu. This may be related to Flu oxidation with KMnO4 . There is a linear relationship between the decrease in CL intensity and the Flu concentration over a range of 2-300 µg/L. A new simple, rapid and sensitive CL method was developed for the determination of Flu with a detection limit (3s) of 1.35 µg/L. The proposed method was used for the determination of Flu in pharmaceutical and urine samples. Copyright © 2014 John Wiley & Sons, Ltd.

mir-200c Regulates Induction of Apoptosis through CD95 by Targeting FAP-1

PubMed Central

Schickel, Robert; Park, Sun-Mi; Murmann, Andrea E.; Peter, Marcus E.

2010-01-01

SUMMARY Tumor progression shares many characteristics with the process of epithelial-to-mesenchymal transition (EMT). Cells that have undergone an EMT are known to have an increased resistance to apoptosis. CD95/Fas is an apoptosis-inducing receptor expressed on many tissues and tumor cells. During tumor progression CD95 is frequently downregulated, and tumor cells lose apoptosis sensitivity. miR-200 microRNAs repress both the EMT-inducing ZEB1 and ZEB2 transcription factors. We now demonstrate that miR-200c sensitizes cells to apoptosis mediated by CD95. We have identified the apoptosis inhibitor FAP-1 as a target for miR-200c. FAP-1 was demonstrated to be responsible for the reduced sensitivity to CD95-mediated apoptosis in cells with inhibited miR-200. The identification of FAP-1 as a miR-200c target provides a molecular mechanism to explain both the downregulation of CD95 expression and the reduction in sensitivity of cells to CD95-mediated apoptosis that is observed in the context of reduced miR-200 expression during tumor progression. PMID:20620960

Ryk receptor regulates hematopoietic stem and progenitor sensitivity to myelosuppressive injury in mice

PubMed Central

Povinelli, Benjamin J.; Srivastava, Pragya; Nemeth, Michael J.

2017-01-01

Maintaining a careful balance between quiescence and proliferation of hematopoietic stem and progenitor cells (HSPCs) is necessary for lifelong blood formation. Previously, we demonstrated that the Wnt5a ligand inhibits HSPC proliferation through a functional interaction with a non-canonical Wnt ligand receptor termed Ryk. Expression of Ryk on HSPCs in vivo is associated with a lower rate of proliferation and following treatment with fluorouracil (5-FU), the percentage of Ryk+/high HSPCs increased while the percent of Ryk−/low HSPCs decreased. Based on these data, we hypothesized that one function of the Ryk receptor is to protect HSPCs from the effects of myeloablative agents. We found that Ryk expression on HSPCs is associated with lower rates of apoptosis following 5-FU and radiation. Transient inhibition of Ryk signaling in vivo resulted in increased HSC proliferation and decreased HSC function in bone marrow transplant assays. Furthermore, inhibition of Ryk signaling sensitized HSPCs to 5-FU treatment in association with increased levels of reactive oxygen species. Together, these results demonstrated an association between Ryk expression and survival of HSPCs following suppressive injury. PMID:25461251

Novel Primer Sets for Next Generation Sequencing-Based Analyses of Water Quality

PubMed Central

Lee, Elvina; Khurana, Maninder S.; Whiteley, Andrew S.; Monis, Paul T.; Bath, Andrew; Gordon, Cameron; Ryan, Una M.; Paparini, Andrea

2017-01-01

Next generation sequencing (NGS) has rapidly become an invaluable tool for the detection, identification and relative quantification of environmental microorganisms. Here, we demonstrate two new 16S rDNA primer sets, which are compatible with NGS approaches and are primarily for use in water quality studies. Compared to 16S rRNA gene based universal primers, in silico and experimental analyses demonstrated that the new primers showed increased specificity for the Cyanobacteria and Proteobacteria phyla, allowing increased sensitivity for the detection, identification and relative quantification of toxic bloom-forming microalgae, microbial water quality bioindicators and common pathogens. Significantly, Cyanobacterial and Proteobacterial sequences accounted for ca. 95% of all sequences obtained within NGS runs (when compared to ca. 50% with standard universal NGS primers), providing higher sensitivity and greater phylogenetic resolution of key water quality microbial groups. The increased selectivity of the new primers allow the parallel sequencing of more samples through reduced sequence retrieval levels required to detect target groups, potentially reducing NGS costs by 50% but still guaranteeing optimal coverage and species discrimination. PMID:28118368

Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

PubMed

Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

2008-12-01

Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring.

High hunger state increases olfactory sensitivity to neutral but not food odors.

PubMed

Stafford, Lorenzo D; Welbeck, Kimberley

2011-01-01

Understanding how hunger state relates to olfactory sensitivity has become more urgent due to their possible role in obesity. In 2 studies (within-subjects: n = 24, between-subjects: n = 40), participants were provided with lunch before (satiated state) or after (nonsatiated state) testing and completed a standardized olfactory threshold test to a neutral odor (Experiments 1 and 2) and discrimination test to a food odor (Experiment 2). Experiment 1 revealed that olfactory sensitivity was greater in the nonsatiated versus satiated state, with additionally increased sensitivity for the low body mass index (BMI) compared with high BMI group. Experiment 2 replicated this effect for neutral odors, but in the case of food odors, those in a satiated state had greater acuity. Additionally, whereas the high BMI group had higher acuity to food odors in the satiated versus nonsatiated state, no such differences were found for the low BMI group. The research here is the first to demonstrate how olfactory acuity changes as a function of hunger state and relatedness of odor to food and that BMI can predict differences in olfactory sensitivity.

The development of cortical sensitivity to visual word forms.

PubMed

Ben-Shachar, Michal; Dougherty, Robert F; Deutsch, Gayle K; Wandell, Brian A

2011-09-01

The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7-12 years old. The results show age-related increase in children's cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition.

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

PubMed Central

Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

2016-01-01

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension.

PubMed

Liu, Yunmeng; Rafferty, Tonya M; Rhee, Sung W; Webber, Jessica S; Song, Li; Ko, Benjamin; Hoover, Robert S; He, Beixiang; Mu, Shengyu

2017-01-09

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8 + T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8 + T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8 + T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K + channel Kir4.1, and stimulation of the Cl - channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.

CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension

PubMed Central

Liu, Yunmeng; Rafferty, Tonya M.; Rhee, Sung W.; Webber, Jessica S.; Song, Li; Ko, Benjamin; Hoover, Robert S.; He, Beixiang; Mu, Shengyu

2017-01-01

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8+ T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8+ T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8+ T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K+ channel Kir4.1, and stimulation of the Cl− channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension. PMID:28067240

The Development of Cortical Sensitivity to Visual Word Forms

PubMed Central

Ben-Shachar, Michal; Dougherty, Robert F.; Deutsch, Gayle K.; Wandell, Brian A.

2011-01-01

The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7–12 years old. The results show age-related increase in children's cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition. PMID:21261451

One versus five-days of exposure to varying concentrations of B100 soya biodiesel exhaust reveals a threshold concentration for increased sensitivity to aconitine-induced arrhythmia

EPA Science Inventory

Although biodiesel (BD) is rapidly being considered as an alternative to diesel fuel, its health effects have not been thoroughly characterized. We previously used the aconitine challenge test to demonstrate that a single exposure to petroleum diesel exhaust (DE) increases the ri...

Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease

EPA Science Inventory

Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) are among those with an increased sensitivity to air p...

EOSINOPHIL INFLUX TO THE NASAL AIRWAY FOLLOWING LOCAL, LOW-LEVEL LPS CHALLENGE IN HUMANS

EPA Science Inventory

Background: Recent obervations show that atopic asthmatic subjects have increased sensitivity to respirable endotoxin (or LPS) compared with normal persons. In vitro studies demonstrate that LPS enchances eosinophil survival. These obervations suggest that the effects of inhal...

Sensitivity and Specificity of Biochemical Tests for Diagnosis of Intrahepatic Cholestasis of Pregnancy.

PubMed

Jurate, Kondrackiene; Rimantas, Zalinkevicius; Jolanta, Sumskiene; Vladas, Gintautas; Limas, Kupcinskas

2017-01-01

Intrahepatic cholestasis of pregnancy (ICP) is linked with increased risk of fetal complications. An accurate diagnostic test is needed to diagnose this disorder on time. We aimed to assess sensitivity and specificity of laboratory tests used for diagnosis of intrahepatic cholestasis of pregnancy and determine more reliable cut-off values of transaminases. Sixty one symptomatic patients with ICP and 29 healthy pregnant women were included in the retrospective analysis. ICP patients had higher total bile acids (TBA) levels than healthy women (32 vs. 6; P < 0.0001) due to increase in cholic acid (CA) and chenodeoxycholic acid (CDCA). CA/CDCA ratio was significantly higher in ICP patients compared to healthy pregnant women (1.13 vs. 0.68; P < 0.00002). TBA, CA, CDCA and CA/CDCA ratio demonstrate the following sensitivity (94%, 96%, 89%, 71.9%) and specificity (63%, 63%, 59%, 79.3%, respectively) for ICP diagnosis. Lowering cut-off values for ALT (31 U/L) and AST (30 U/L) resulted only in minimal increase of sensitivity to 92.2% vs. 90.1% for ALT and to 92.2%, vs. 90.6% for AST. The present study did not reveal any single specific and sensitive marker for reliable diagnosis of ICP. Establishment of lower cut-off values for transaminases activity might only minimally increase the accuracy of diagnosing ICP.

Telomerase antagonist imetelstat increases radiation sensitivity in esophageal squamous cell carcinoma

PubMed Central

Wu, Xuping; Zhang, Jing; Yang, Sijun; Kuang, Zhihui; Tan, Guolei; Yang, Gang; Wei, Qichun; Guo, Zhigang

2017-01-01

The morbidity and mortality of esophageal cancer is one of the highest around the world and the principal therapeutic method is radiation. Thus, searching for sensitizers with lower toxicity and higher efficiency to improve the efficacy of radiation therapy is critical essential. Our research group has previously reported that imetelstat, the thio-phosphoramidate oligonucleotide inhibitor of telomerase, can decrease cell proliferation and colony formation ability as well as increase DNA breaks induced by radiation in esophageal cancer cells. Further study in this project showed that imetelstat significantly sensitized esophageal cancer cells to radiation in vitro. Later study showed that imetelstat leads to increased cell apoptosis. We also measured the expression level of several DNA repair and apoptosis signaling proteins. pS345 CHK1, γ-H2AX, p53 and caspase3 expression were up-regulated in imetelstat treated cells, identifying these factors as molecular markers. Mouse in vivo model using imetelstat at clinically achievable concentrations and fractionated irradiation scheme yielded results demonstrating radiosensitization effect. Finally, TUNEL assay, caspase 3 and Ki67 staining in tumor tissue proved that imetelstat sensitized esophageal cancer to radiation in vivo through promoting cell apoptosis and inhibiting cell proliferation. Our study supported imetelstat increase radiation sensitivity of esophageal squamous cell carcinoma through inducing cell apoptosis and the specific inhibitor of telomerase might serve as a potential novel therapeutic tool for esophageal squamous cell carcinoma therapy. PMID:28099140

Telomerase antagonist imetelstat increases radiation sensitivity in esophageal squamous cell carcinoma.

PubMed

Wu, Xuping; Zhang, Jing; Yang, Sijun; Kuang, Zhihui; Tan, Guolei; Yang, Gang; Wei, Qichun; Guo, Zhigang

2017-02-21

The morbidity and mortality of esophageal cancer is one of the highest around the world and the principal therapeutic method is radiation. Thus, searching for sensitizers with lower toxicity and higher efficiency to improve the efficacy of radiation therapy is critical essential. Our research group has previously reported that imetelstat, the thio-phosphoramidate oligonucleotide inhibitor of telomerase, can decrease cell proliferation and colony formation ability as well as increase DNA breaks induced by radiation in esophageal cancer cells. Further study in this project showed that imetelstat significantly sensitized esophageal cancer cells to radiation in vitro. Later study showed that imetelstat leads to increased cell apoptosis. We also measured the expression level of several DNA repair and apoptosis signaling proteins. pS345 CHK1, γ-H2AX, p53 and caspase3 expression were up-regulated in imetelstat treated cells, identifying these factors as molecular markers. Mouse in vivo model using imetelstat at clinically achievable concentrations and fractionated irradiation scheme yielded results demonstrating radiosensitization effect. Finally, TUNEL assay, caspase 3 and Ki67 staining in tumor tissue proved that imetelstat sensitized esophageal cancer to radiation in vivo through promoting cell apoptosis and inhibiting cell proliferation. Our study supported imetelstat increase radiation sensitivity of esophageal squamous cell carcinoma through inducing cell apoptosis and the specific inhibitor of telomerase might serve as a potential novel therapeutic tool for esophageal squamous cell carcinoma therapy.

Sensitivity analysis for dose deposition in radiotherapy via a Fokker–Planck model

DOE PAGES

Barnard, Richard C.; Frank, Martin; Krycki, Kai

2016-02-09

In this paper, we study the sensitivities of electron dose calculations with respect to stopping power and transport coefficients. We focus on the application to radiotherapy simulations. We use a Fokker–Planck approximation to the Boltzmann transport equation. Equations for the sensitivities are derived by the adjoint method. The Fokker–Planck equation and its adjoint are solved numerically in slab geometry using the spherical harmonics expansion (P N) and an Harten-Lax-van Leer finite volume method. Our method is verified by comparison to finite difference approximations of the sensitivities. Finally, we present numerical results of the sensitivities for the normalized average dose depositionmore » depth with respect to the stopping power and the transport coefficients, demonstrating the increase in relative sensitivities as beam energy decreases. In conclusion, this in turn gives estimates on the uncertainty in the normalized average deposition depth, which we present.« less

Coupled resonator optical waveguide sensors: sensitivity and the role of slow light

NASA Astrophysics Data System (ADS)

Terrel, Matthew A.; Digonnet, Michel J. F.; Fan, Shanhui

2009-05-01

We compare the sensitivity of two configurations of coupled resonator optical waveguide (CROW) gyroscopes proposed by others to conventional optical gyroscopes. In both cases, we demonstrate that for equal device footprint and loss, neither of these CROW gyroscopes configurations is more sensitive than its conventional counterpart. In all cases, loss ultimately limits the maximum rotation sensitivity. The fact that light travels more slowly (i.e., with a greater group delay) in a CROW than in a fiber therefore has no effect on sensitivity. The only benefit slow light does have is that it reduces the device length requirement, or equivalently it increases the sensitivity per unit length. However, we show that this improvement is quantitatively the same as in an RFOG. These conclusions are not limited to these two CROW configurations or to rotation sensing, but applicable to any measurand that modifies the phase of the signal(s) traveling in the resonators.

Poly(ADP-ribose) polymerase inhibitors sensitize cancer cells to death receptor-mediated apoptosis by enhancing death receptor expression.

PubMed

Meng, X Wei; Koh, Brian D; Zhang, Jin-San; Flatten, Karen S; Schneider, Paula A; Billadeau, Daniel D; Hess, Allan D; Smith, B Douglas; Karp, Judith E; Kaufmann, Scott H

2014-07-25

Recombinant human tumor necrosis factor-α-related apoptosis inducing ligand (TRAIL), agonistic monoclonal antibodies to TRAIL receptors, and small molecule TRAIL receptor agonists are in various stages of preclinical and early phase clinical testing as potential anticancer drugs. Accordingly, there is substantial interest in understanding factors that affect sensitivity to these agents. In the present study we observed that the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and veliparib sensitize the myeloid leukemia cell lines ML-1 and K562, the ovarian cancer line PEO1, non-small cell lung cancer line A549, and a majority of clinical AML isolates, but not normal marrow, to TRAIL. Further analysis demonstrated that PARP inhibitor treatment results in activation of the FAS and TNFRSF10B (death receptor 5 (DR5)) promoters, increased Fas and DR5 mRNA, and elevated cell surface expression of these receptors in sensitized cells. Chromatin immunoprecipitation demonstrated enhanced binding of the transcription factor Sp1 to the TNFRSF10B promoter in the presence of PARP inhibitor. Knockdown of PARP1 or PARP2 (but not PARP3 and PARP4) not only increased expression of Fas and DR5 at the mRNA and protein level, but also recapitulated the sensitizing effects of the PARP inhibition. Conversely, Sp1 knockdown diminished the PARP inhibitor effects. In view of the fact that TRAIL is part of the armamentarium of natural killer cells, these observations identify a new facet of PARP inhibitor action while simultaneously providing the mechanistic underpinnings of a novel therapeutic combination that warrants further investigation.

Voltage-sensitive rhodol with enhanced two-photon brightness

PubMed Central

Kulkarni, Rishikesh U.; Kramer, Daniel J.; Pourmandi, Narges; Karbasi, Kaveh; Bateup, Helen S.

2017-01-01

We have designed, synthesized, and applied a rhodol-based chromophore to a molecular wire-based platform for voltage sensing to achieve fast, sensitive, and bright voltage sensing using two-photon (2P) illumination. Rhodol VoltageFluor-5 (RVF5) is a voltage-sensitive dye with improved 2P cross-section for use in thick tissue or brain samples. RVF5 features a dichlororhodol core with pyrrolidyl substitution at the nitrogen center. In mammalian cells under one-photon (1P) illumination, RVF5 demonstrates high voltage sensitivity (28% ΔF/F per 100 mV) and improved photostability relative to first-generation voltage sensors. This photostability enables multisite optical recordings from neurons lacking tuberous sclerosis complex 1, Tsc1, in a mouse model of genetic epilepsy. Using RVF5, we show that Tsc1 KO neurons exhibit increased activity relative to wild-type neurons and additionally show that the proportion of active neurons in the network increases with the loss of Tsc1. The high photostability and voltage sensitivity of RVF5 is recapitulated under 2P illumination. Finally, the ability to chemically tune the 2P absorption profile through the use of rhodol scaffolds affords the unique opportunity to image neuronal voltage changes in acutely prepared mouse brain slices using 2P illumination. Stimulation of the mouse hippocampus evoked spiking activity that was readily discerned with bath-applied RVF5, demonstrating the utility of RVF5 and molecular wire-based voltage sensors with 2P-optimized fluorophores for imaging voltage in intact brain tissue. PMID:28242676

Injectable and body temperature sensitive hydrogels based on chitosan and hyaluronic acid for pH sensitive drug release.

PubMed

Zhang, Wei; Jin, Xin; Li, Heng; Zhang, Run-Run; Wu, Cheng-Wei

2018-04-15

Hydrogels based on chitosan/hyaluronic acid/β-sodium glycerophosphate demonstrate injectability, body temperature sensitivity, pH sensitive drug release and adhesion to cancer cell. The drug (doxorubicin) loaded hydrogel precursor solutions are injectable and turn to hydrogels when the temperature is increased to body temperature. The acidic condition (pH 4.00) can trigger the release of drug and the cancer cell (Hela) can adhere to the surface of the hydrogels, which will be beneficial for tumor site-specific administration of drug. The mechanical strength, the gelation temperature, and the drug release behavior can be tuned by varying hyaluronic acid content. The mechanisms were characterized using dynamic mechanical analysis, Fourier transform infrared spectroscopy, scanning electron microscopy and fluorescence microscopy. The carboxyl group in hyaluronic acid can form the hydrogen bondings with the protonated amine in chitosan, which promotes the increase of mechanical strength of the hydrogels and depresses the initial burst release of drug from the hydrogel. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anxiety, its relation to symptoms severity and anxiety sensitivity in sarcoidosis.

PubMed

Holas, Pawel; Krejtz, Izabela; Urbankowski, Tomasz; Skowyra, Artur; Ludwiniak, Anna; Domagala-Kulawik, Joanna

2013-12-17

Sarcoidosis is a chronic systemic granulomatous disease of unknown etiology. Previous studies demonstrated that patients with sarcoidosis had high rates of depression and anxiety, and high magnitude of stressful life events. To date, however, studies have not examined the anxiety sensitivity in sarcoid patients and the relationship between psychopathology and symptom severity of sarcoidosis.The aims of this study were to evaluate prevalence of depression and anxiety in sarcoid patients, to assess their relationship with the disease symptom severity, and to investigate the relationship between sarcoidosis and anxiety sensitivity. Thirty three sarcoid patients and thirty three control subjects completed the following:Hospital Anxiety and Depression Scale, Anxiety Sensitivity Index-3. The prevalence of depression (29%) and anxiety (31%) was high among patients and comparable to results from other research groups. Anxiety was significantly correlated with symptom severity and was the main covariate of physical symptoms reported by sarcoid patients. Patients exhibited an increase of their total anxiety sensitivity index and had an increased number of physical concerns. These data confirmed earlier reports that anxiety and depression are common in patients with sarcoidosis and expanded on the previous results by showing that patients exhibited increased anxiety sensitivity and a fear of physical sensations. These results, together with the findings that anxiety was associated with sarcoidosis symptom severity, suggest that targeting anxiety and the physical health concerns may be important in the diagnosis and management of this disease.

Volatile Organic Compounds Enhance Allergic Airway Inflammation in an Experimental Mouse Model

PubMed Central

Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C.; Lehmann, Irina; Polte, Tobias

2012-01-01

Background Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. Methods To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Results Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Conclusions Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases. PMID:22802943

Volatile organic compounds enhance allergic airway inflammation in an experimental mouse model.

PubMed

Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C; Lehmann, Irina; Polte, Tobias

2012-01-01

Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases.

The impact of detergents on the tissue decellularization process: A ToF-SIMS study.

PubMed

White, Lisa J; Taylor, Adam J; Faulk, Denver M; Keane, Timothy J; Saldin, Lindsey T; Reing, Janet E; Swinehart, Ilea T; Turner, Neill J; Ratner, Buddy D; Badylak, Stephen F

2017-03-01

Biologic scaffolds are derived from mammalian tissues, which must be decellularized to remove cellular antigens that would otherwise incite an adverse immune response. Although widely used clinically, the optimum balance between cell removal and the disruption of matrix architecture and surface ligand landscape remains a considerable challenge. Here we describe the use of time of flight secondary ion mass spectroscopy (ToF-SIMS) to provide sensitive, molecular specific, localized analysis of detergent decellularized biologic scaffolds. We detected residual detergent fragments, specifically from Triton X-100, sodium deoxycholate and sodium dodecyl sulphate (SDS) in decellularized scaffolds; increased SDS concentrations from 0.1% to 1.0% increased both the intensity of SDS fragments and adverse cell outcomes. We also identified cellular remnants, by detecting phosphate and phosphocholine ions in PAA and CHAPS decellularized scaffolds. The present study demonstrates ToF-SIMS is not only a powerful tool for characterization of biologic scaffold surface molecular functionality, but also enables sensitive assessment of decellularization efficacy. We report here on the use of a highly sensitive analytical technique, time of flight secondary ion mass spectroscopy (ToF-SIMS) to characterize detergent decellularized scaffolds. ToF-SIMS detected cellular remnants and residual detergent fragments; increased intensity of the detergent fragments correlated with adverse cell matrix interactions. This study demonstrates the importance of maintaining a balance between cell removal and detergent disruption of matrix architecture and matrix surface ligand landscape. This study also demonstrates the power of ToF-SIMS for the characterization of decellularized scaffolds and capability for assessment of decellularization efficacy. Future use of biologic scaffolds in clinical tissue reconstruction will benefit from the fundamental results described in this work. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Interplay of Filaggrin Loss-of-Function Variants, Allergic Sensitization, and Eczema in a Longitudinal Study Covering Infancy to 18 Years of Age

PubMed Central

Ziyab, Ali H.; Karmaus, Wilfried; Yousefi, Mitra; Ewart, Susan; Schauberger, Eric; Holloway, John W.; Zhang, Hongmei; Arshad, Syed Hasan

2012-01-01

Background Immune specific genes as well as genes regulating the formation of skin barrier are major determinants for eczema manifestation. There is a debate as to whether allergic sensitization and filaggrin gene (FLG) variants lead to eczema or FLG variants and eczema increase the risk of allergic sensitization. To investigate the time-order between eczema and allergic sensitization with respect to FLG variants, data from a large prospective study covering infancy to late adolescence were analyzed. Methodology/Principal Findings Repeated measurements of eczema and allergic sensitization (documented by skin prick tests) at ages 1, 2, 4, 10, and 18 years were ascertained in the Isle of Wight birth cohort (n = 1,456). Three transition periods were analyzed: age 1-or-2 to 4, 4 to 10, and 10 to 18 years. FLG variants were genotyped in 1,150 participants. Over the three transition periods, in temporal sequence analyses of initially eczema-free participants, the combined effect of FLG variants and allergic sensitization showed a 2.92-fold (95% CI: 1.47–5.77) increased risk ratio (RR) of eczema in subsequent examinations. This overall risk was more pronounced at a younger age (transition period 1-or-2 to 4, RR = 6.47, 95% CI: 1.96–21.33). In contrast, FLG variants in combination with eczema showed a weaker, but significant, risk ratio for subsequent allergic sensitization only up to 10 years of age. Conclusions/Significance Taking the time order into account, this prospective study demonstrates for the first time, that a combination of FLG variants and allergic sensitization increased the risk of eczema in subsequent years. Also FLG variants interacted with eczema and increased the risk of subsequent allergic sensitization, which, was limited to the younger age. Hence, early restoration of defective skin barrier could prevent allergic sensitization and subsequently reduce the risk of eczema development. PMID:22403702

Increasing biopsy number and sampling from gastric body improve the sensitivity of rapid urease test in patients with peptic ulcer bleeding.

PubMed

Lee, Tzong-Hsi; Lin, Chien-Chu; Chung, Chen-Shuan; Lin, Cheng-Kuan; Liang, Cheng-Chao; Tsai, Kuang-Chau

2015-02-01

Previous studies demonstrated that the sensitivity of rapid urease test (RUT) for diagnosis of Helicobacter pylori infection decreased during peptic ulcer bleeding. We designed this study and tried to find a better method to improve the detection rate of H. pylori infection at the same session of endoscopic diagnosis of peptic ulcer bleeding. We prospectively enrolled 116 patients with peptic ulcer bleeding. These patients received intravenous proton pump inhibitor and then received upper gastrointestinal endoscopy within 24 h after arrival. We took one piece of biopsy from gastric antrum (Group 1), four pieces from gastric antrum (Group 2), and one piece from the gastric body (Group 3) for three separate RUTs, respectively. (13)C-urease breath test was used as gold standard for diagnosis of H. pylori infection. There were 74 patients (64 %) with positive (13)C-urease breath test. Among these 74 patients, 45 patients had positive RUT (sensitivity: 61 %) in Group 1; 55 patients had positive RUT (sensitivity: 74 %) in Group 2; 54 patients had positive RUT (sensitivity: 73 %) in Group 3. There were significant differences between Group 1 and Group 2 (p = 0.02) and between Group 1 and Group 3 (p = 0.022). The sensitivity of RUT was 61 % during peptic ulcer bleeding. The sensitivity of RUT can be increased significantly by increased biopsy number from gastric antrum or biopsy from gastric body.

Specific features of the planarian Dugesia tigrina regeneration and mollusk Helix albescens nociception under weak electromagnetic shielding

NASA Astrophysics Data System (ADS)

Temur'yants, N. A.; Demtsun, N. A.; Kostyuk, A. S.; Yarmolyuk, N. S.

2012-12-01

It has been demonstrated that weak electromagnetic shielding stimulates regeneration in the planarian Dugesia tigrina, the stimulating intensity being dependent on both the initial state of the animals, which is determined by season, and their functional asymmetry. As has been shown, the effect of a weak electromagnetic field induces phasic changes in the nociceptive sensitivity of the mollusk Helix albescens: an increase in the sensitivity to a thermal stimulus is replaced by the development of the hypalgesic effect.

Geometrical optimization of a local ballistic magnetic sensor

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

Kanda, Yuhsuke; Hara, Masahiro; Nomura, Tatsuya

2014-04-07

We have developed a highly sensitive local magnetic sensor by using a ballistic transport property in a two-dimensional conductor. A semiclassical simulation reveals that the sensitivity increases when the geometry of the sensor and the spatial distribution of the local field are optimized. We have also experimentally demonstrated a clear observation of a magnetization process in a permalloy dot whose size is much smaller than the size of an optimized ballistic magnetic sensor fabricated from a GaAs/AlGaAs two-dimensional electron gas.

Tyrosinase overexpression promotes ATM-dependent p53 phosphorylation by quercetin and sensitizes melanoma cells to dacarbazine.

PubMed

Thangasamy, Thilakavathy; Sittadjody, Sivanandane; Limesand, Kirsten H; Burd, Randy

2008-01-01

Dacarbazine (DTIC) has been used for the treatment of melanoma for decades. However, monotherapy with this chemotherapeutic agent results only in moderate response rates. To improve tumor response to DTIC current clinical trials in melanoma focus on combining a novel targeted agent with chemotherapy. Here, we demonstrate that tyrosinase which is commonly overexpressed in melanoma activates the bioflavonoid quercetin (Qct) and promotes an ataxia telangiectasia mutated (ATM)-dependent DNA damage response. This response sensitizes melanoma cells that overexpress tyrosinase to DTIC. In DB-1 melanoma cells that overexpress tyrosinase (Tyr(+) cells), the threshold for phosphorylation of ATM and p53 at serine 15 was observed at a low dose of Qct (25 microM) when compared to the mock transfected pcDNA3 cells, which required a higher dose (75 microM). Both pcDNA3 and Tyr(+) DB-1 cells demonstrated similar increases in phosphorylation of p53 at other serine sites, but in the Tyr(+) cells, DNApk expression was found to be reduced compared to control cells, indicating a shift towards an ATM-mediated response. The DB-1 control cells were resistant to DTIC, but were sensitized to apoptosis with high dose Qct, while Tyr(+) cells were sensitized to DTIC with low or high dose Qct. Qct also sensitized SK Mel 5 (p53 wildtype) and 28 (p53 mutant) cells to DTIC. However, when SK Mel 5 cells were transiently transfected with tyrosinase and treated with Qct plus DTIC, SK Mel 5 cells demonstrated a more than additive induction of apoptosis. Therefore, this study demonstrates that tyrosinase overexpression promotes an ATM-dependent p53 phosphorylation by Qct treatment and sensitizes melanoma cells to dacarbazine. In conclusion, these results suggest that Qct or Qct analogues may significantly improve DTIC response rates in tumors that express tyrosinase.

Tyrosinase Overexpression Promotes ATM-Dependent p53 Phosphorylation by Quercetin and Sensitizes Melanoma Cells to Dacarbazine

PubMed Central

Thangasamy, Thilakavathy; Sittadjody, Sivanandane; H. Limesand, Kirsten; Burd, Randy

2008-01-01

Dacarbazine (DTIC) has been used for the treatment of melanoma for decades. However, monotherapy with this chemotherapeutic agent results only in moderate response rates. To improve tumor response to DTIC current clinical trials in melanoma focus on combining a novel targeted agent with chemotherapy. Here, we demonstrate that tyrosinase which is commonly overexpressed in melanoma activates the bioflavonoid quercetin (Qct) and promotes an ataxia telangiectasia mutated (ATM)-dependent DNA damage response. This response sensitizes melanoma cells that overexpress tyrosinase to DTIC. In DB-1 melanoma cells that overexpress tyrosinase (Tyr cells), the threshold for phosphorylation of ATM and p53 at serine 15 was observed at a low dose of Qct (25 μM) when compared to the mock transfected pcDNA3 cells, which required a higher dose (75 μM). Both pcDNA3 and Tyr DB-1 cells demonstrated similar increases in phosphorylation of p53 at other serine sites, but in the Tyr cells, DNApk expression was found to be reduced compared to control cells, indicating a shift towards an ATM-mediated response. The DB-1 control cells were resistant to DTIC, but were sensitized to apoptosis with high dose Qct, while Tyr cells were sensitized to DTIC with low or high dose Qct. Qct also sensitized SK Mel 5 (p53 wildtype) and 28 (p53 mutant) cells to DTIC. However, when SK Mel 5 cells were transiently transfected with tyrosinase and treated with Qct plus DTIC, SK Mel 5 cells demonstrated a more than additive induction of apoptosis. Therefore, this study demonstrates that tyrosinase overexpression promotes an ATM-dependent p53 phosphorylation by Qct treatment and sensitizes melanoma cells to dacarbazine. In conclusion, these results suggest that Qct or Qct analogues may significantly improve DTIC response rates in tumors that express tyrosinase. PMID:18791269

Improved detection of endoparasite DNA in soil sample PCR by the use of anti-inhibitory substances.

PubMed

Krämer, F; Vollrath, T; Schnieder, T; Epe, C

2002-09-26

Although there have been numerous microbial examinations of soil for the presence of human pathogenic developmental parasite stages of Ancylostoma caninum and Toxocara canis, molecular techniques (e.g. DNA extraction, purification and subsequent PCR) have scarcely been applied. Here, DNA preparations of soil samples artificially contaminated with genomic DNA or parasite eggs were examined by PCR. A. caninum and T. canis-specific primers based on the ITS-2 sequence were used for amplification. After the sheer DNA preparation a high content of PCR-interfering substances was still detectable. Subsequently, two different inhibitors of PCR-interfering agents (GeneReleaser, Bioventures Inc. and Maximator, Connex GmbH) were compared in PCR. Both substances increased PCR sensitivity greatly. However, comparison of the increase in sensitivity achieved with the two compounds demonstrated the superiority of Maximator, which enhanced sensitivity to the point of permitting positive detection of a single A. caninum egg and three T. canis eggs in a soil sample. This degree of sensitivity could not be achieved with GeneReleaser for either parasite Furthermore, Maximator not only increased sensitivity; it also cost less, required less time and had a lower risk of contamination. Future applications of molecular methods in epidemiological examinations of soil samples are discussed/elaborated.

Cross-reactivity of Halogenated Platinum Salts | Science ...

EPA Pesticide Factsheets

Halogenated platinum (Pt) salts are well-known respiratory sensitizers associated with the development of asthma. People may be exposed to a variety of platinum compounds in different contexts (e.g. occupationally, automobile exhaust). Published reports suggest that sensitization to one Pt compound may result in hypersensitivity reactions to other Pt compounds. We investigated the potential for this type of cross-reactivity using a mouse model of Pt hypersensitivity. Mice were sensitized through application of 100 µL 1% ammonium hexachloroplatinate (AHCP) in DMSO to the shaved back on days 0, 5 and 19, and 25 µl to each ear on days 10, 11 and 12. Unsensitized mice received vehicle. On day 24, mice were challenged by intratracheal aspiration (IA) with saline or 100 µg AHCP or 100 g ammonium tetrachloroplatinate (ATCP) in saline. Before and immediately after dosing, airway responses were assessed using whole body plethysmography (WBP). On day 26, changes in ventilatory responses to methacholine (Mch) aerosol were assessed by WBP. All mice dosed with AHCP demonstrated significant increases in total serum IgE, suggesting the animals were sensitized. An immediate airway response (IAR) was observed in mice sensitized and challenged with AHCP. Dose-dependent increases in Mch responsiveness occurred in mice sensitized and challenged with AHCP. Bronchoalveolar lavage fluid (BALF) harvested from mice sensitized and challenged with AHCP contained an avera

The mycotoxin deoxynivalenol facilitates allergic sensitization to whey in mice.

PubMed

Bol-Schoenmakers, M; Braber, S; Akbari, P; de Graaff, P; van Roest, M; Kruijssen, L; Smit, J J; van Esch, B C A M; Jeurink, P V; Garssen, J; Fink-Gremmels, J; Pieters, R H H

2016-11-01

Intestinal epithelial stress or damage may contribute to allergic sensitization against certain food antigens. Hence, the present study investigated whether impairment of intestinal barrier integrity by the mycotoxin deoxynivalenol (DON) contributes to the development of whey-induced food allergy in a murine model. C3H/HeOuJ mice, orally exposed to DON plus whey once a week for 5 consecutive weeks, showed whey-specific IgG1 and IgE in serum and an acute allergic skin response upon intradermal whey challenge, although early initiating mechanisms of sensitization in the intestine appeared to be different compared with the widely used mucosal adjuvant cholera toxin (CT). Notably, DON exposure modulated tight-junction mRNA and protein levels, and caused an early increase in IL-33, whereas CT exposure affected intestinal γδ T cells. On the other hand, both DON- and CT-sensitized mice induced a time-dependent increase in the soluble IL-33 receptor ST2 (IL-1R1) in serum, and enhanced local innate lymphoid cells type 2 cell numbers. Together, these results demonstrate that DON facilitates allergic sensitization to food proteins and that development of sensitization can be induced by different molecular mechanisms and local immune responses. Our data illustrate the possible contribution of food contaminants in allergic sensitization in humans.

Altered sensitization patterns to sweet food stimuli in patients recovered from anorexia and bulimia nervosa.

PubMed

Wagner, Angela; Simmons, Alan N; Oberndorfer, Tyson A; Frank, Guido K W; McCurdy-McKinnon, Danyale; Fudge, Julie L; Yang, Tony T; Paulus, Martin P; Kaye, Walter H

2015-12-30

Recent studies show that higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa (AN) and overeating in bulimia nervosa (BN). The purpose of this study was to determine whether sensitization effects might underlie pathologic eating behavior when a taste stimulus is administered repeatedly. Recovered AN (RAN, n=14) and BN (RBN, n=15) subjects were studied in order to avoid the confounding effects of altered nutritional state. Functional magnetic resonance imaging (fMRI) measured higher-order brain response to repeated tastes of sucrose (caloric) and sucralose (non-caloric). To test sensitization, the neuronal response to the first and second administration was compared. RAN patients demonstrated a decreased sensitization to sucrose in contrast to RBN patients who displayed the opposite pattern, increased sensitization to sucrose. However, the latter was not as pronounced as in healthy control women (n=13). While both eating disorder subgroups showed increased sensitization to sucralose, the healthy controls revealed decreased sensitization. These findings could reflect on a neuronal level the high caloric intake of RBN during binges and the low energy intake for RAN. RAN seem to distinguish between high energy and low energy sweet stimuli while RBN do not. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Anomaly metrics to differentiate threat sources from benign sources in primary vehicle screening.

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

Cohen, Israel Dov; Mengesha, Wondwosen

2011-09-01

Discrimination of benign sources from threat sources at Port of Entries (POE) is of a great importance in efficient screening of cargo and vehicles using Radiation Portal Monitors (RPM). Currently RPM's ability to distinguish these radiological sources is seriously hampered by the energy resolution of the deployed RPMs. As naturally occurring radioactive materials (NORM) are ubiquitous in commerce, false alarms are problematic as they require additional resources in secondary inspection in addition to impacts on commerce. To increase the sensitivity of such detection systems without increasing false alarm rates, alarm metrics need to incorporate the ability to distinguish benign andmore » threat sources. Principal component analysis (PCA) and clustering technique were implemented in the present study. Such techniques were investigated for their potential to lower false alarm rates and/or increase sensitivity to weaker threat sources without loss of specificity. Results of the investigation demonstrated improved sensitivity and specificity in discriminating benign sources from threat sources.« less

Contact sensitizing potential of pyrogallol and 5-amino-o-cresol in female BALB/c Mice

PubMed Central

Guo, T.L.; Germolec, D.R.; Zhang, Ling X.; Auttachoat, W.; Smith, M.J.; White, K.L.

2013-01-01

Hair dye components such as pyrogallol and cresol have been shown previously to promote allergic reactions such as rashes, dermal inflammation, irritation and dermatitis. The objective of this study was to determine the contact sensitization potential of pyrogallol (PYR) and 5-amino-o-cresol (AOC) when applied dermally to female BALB/c mice. Measurement of the contact hypersensitivity response was initially accomplished using the local lymph node assay. For PYR, significant increases in the proliferation of lymph node cells were observed at concentrations of 0.5% (w/v) and higher. For AOC, borderline increases, albeit significant, in auricular lymph node cell proliferation were observed at 5% and 10%. Results from the irritancy assay suggested that PYR, but not AOC, was an irritant. To further delineate whether PYR was primarily an irritant or a contact sensitizer, the mouse ear swelling test (MEST) was conducted. A significant increase in mouse ear thickness was observed at 72 hr following challenge with 0.5% PYR in mice that had been sensitized with 5% PYR. In contrast, no effects were observed in the MEST in mice sensitized and challenged with the highest achievable concentration of AOC (10%). Additional studies examining lymph node subpopulations and CD86 (B7.2) expression by B cells further support the indication that PYR was a sensitizer in BALB/c mice. The results demonstrate that PYR is both a sensitizer and an irritant in female BALB/c mice. However, the contact sensitization potential of AOC is minimal in this strain of mouse. PMID:24172597

Stand-off detection of trace explosives by infrared photothermal imaging

NASA Astrophysics Data System (ADS)

Papantonakis, Michael R.; Kendziora, Chris; Furstenberg, Robert; Stepnowski, Stanley V.; Rake, Matthew; Stepnowski, Jennifer; McGill, R. Andrew

2009-05-01

We have developed a technique for the stand-off detection of trace explosives using infrared photothermal imaging. In this approach, infrared quantum cascade lasers tuned to strong vibrational absorption bands of the explosive particles illuminate a surface of interest, preferentially heating the explosives material. An infrared focal plane array is used to image the surface and detect a small increase in the thermal intensity upon laser illumination. We have demonstrated the technique using TNT and RDX residues at several meters of stand-off distance under laboratory conditions, while operating the lasers below the eye-safe intensity limit. Sensitivity to explosives traces as small as a single grain (~100 ng) of TNT has been demonstrated using an uncooled bolometer array. We show the viability of this approach on a variety of surfaces which transmit, reflect or absorb the infrared laser light and have a range of thermal conductivities. By varying the incident wavelength slightly, we demonstrate selectivity between TNT and RDX. Using a sequence of lasers at different wavelengths, we increase both sensitivity and selectivity while reducing the false alarm rate. At higher energy levels we also show it is possible to generate vapor from solid materials with inherently low vapor pressures.

Kir6.2 Variant E23K Increases ATP-Sensitive K+ Channel Activity and Is Associated With Impaired Insulin Release and Enhanced Insulin Sensitivity in Adults With Normal Glucose Tolerance

PubMed Central

Villareal, Dennis T.; Koster, Joseph C.; Robertson, Heather; Akrouh, Alejandro; Miyake, Kazuaki; Bell, Graeme I.; Patterson, Bruce W.; Nichols, Colin G.; Polonsky, Kenneth S.

2009-01-01

OBJECTIVE The E23K variant in the Kir6.2 subunit of the ATP-sensitive K+ channel (KATP channel) is associated with increased risk of type 2 diabetes. The present study was undertaken to increase our understanding of the mechanisms responsible. To avoid confounding effects of hyperglycemia, insulin secretion and action were studied in subjects with the variant who had normal glucose tolerance. RESEARCH DESIGN AND METHODS Nine subjects with the E23K genotype K/K and nine matched subjects with the E/E genotype underwent 5-h oral glucose tolerance tests (OGTTs), graded glucose infusion, and hyperinsulinemic-euglycemic clamp with stable-isotope–labeled tracer infusions to assess insulin secretion, action, and clearance. A total of 461 volunteers consecutively genotyped for the E23K variant also underwent OGTTs. Functional studies of the wild-type and E23K variant potassium channels were conducted. RESULTS Insulin secretory responses to oral and intravenous glucose were reduced by ∼40% in glucose-tolerant subjects homozygous for E23K. Normal glucose tolerance with reduced insulin secretion suggests a change in insulin sensitivity. The hyperinsulinemic-euglycemic clamp revealed that hepatic insulin sensitivity is ∼40% greater in subjects with the E23K variant, and these subjects demonstrate increased insulin sensitivity after oral glucose. The reconstituted E23K channels confirm reduced sensitivity to inhibitory ATP and increase in open probability, a direct molecular explanation for reduced insulin secretion. CONCLUSIONS The E23K variant leads to overactivity of the KATP channel, resulting in reduced insulin secretion. Initially, insulin sensitivity is enhanced, thereby maintaining normal glucose tolerance. Presumably, over time, as insulin secretion falls further or insulin resistance develops, glucose levels rise resulting in type 2 diabetes. PMID:19491206

Multi-flux-transformer MRI detection with an atomic magnetometer.

PubMed

Savukov, Igor; Karaulanov, Todor

2014-12-01

Recently, anatomical ultra-low field (ULF) MRI has been demonstrated with an atomic magnetometer (AM). A flux-transformer (FT) has been used for decoupling MRI fields and gradients to avoid their negative effects on AM performance. The field of view (FOV) was limited because of the need to compromise between the size of the FT input coil and MRI sensitivity per voxel. Multi-channel acquisition is a well-known solution to increase FOV without significantly reducing sensitivity. In this paper, we demonstrate twofold FOV increase with the use of three FT input coils. We also show that it is possible to use a single atomic magnetometer and single acquisition channel to acquire three independent MRI signals by applying a frequency-encoding gradient along the direction of the detection array span. The approach can be generalized to more channels and can be critical for imaging applications of non-cryogenic ULF MRI where FOV needs to be large, including head, hand, spine, and whole-body imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

Multi-flux-transformer MRI detection with an atomic magnetometer

PubMed Central

Savukov, Igor; Karaulanov, Todor

2014-01-01

Recently, anatomical ultra-low field (ULF) MRI has been demonstrated with an atomic magnetometer (AM). A flux-transformer (FT) has been used for decoupling MRI fields and gradients to avoid their negative effects on AM performance. The field of view (FOV) was limited because of the need to compromise between the size of the FT input coil and MRI sensitivity per voxel. Multi-channel acquisition is a well-known solution to increase FOV without significantly reducing sensitivity. In this paper, we demonstrate two-fold FOV increase with the use of three FT input coils. We also show that it is possible to use a single atomic magnetometer and single acquisition channel to acquire three independent MRI signals by applying a frequency-encoding gradient along the direction of the detection array span. The approach can be generalized to more channels and can be critical for imaging applications of non-cryogenic ULF MRI where FOV needs to be large, including head, hand, spine, and whole-body imaging. PMID:25462946

An Enhanced Platform to Analyse Low-Affinity Amyloid β Protein by Integration of Electrical Detection and Preconcentrator.

PubMed

Yoo, Yong Kyoung; Yoon, Dae Sung; Kim, Gangeun; Kim, Jinsik; Han, Sung Il; Lee, Junwoo; Chae, Myung-Sic; Lee, Sang-Myung; Lee, Kyu Hyoung; Hwang, Kyo Seon; Lee, Jeong Hoon

2017-10-30

Sensitivity and limit of detection (LOD) enhancement are essential criteria for the development of ultrasensitive molecular sensors. Although various sensor types have been investigated to enhance sensitivity and LOD, analyte detection and its quantification are still challenging, particularly for protein-protein interactions with low association constants. To solve this problem, here, we used ion concentration polarization (ICP)-based preconcentration to increase the local concentration of analytes in a microfluidic platform for LOD improvement. This was the first demonstration of a microfluidic device with an integrated ICP preconcentrator and interdigitated microelectrode (IME) sensor to detect small changes in surface binding between antigens and antibodies. We detected the amyloid beta (Aβ) protein, an Alzheimer's disease marker, with low binding affinity to its antibodies by adopting ICP preconcentration phenomena. We demonstrated that a combination of ICP preconcentrator and IME sensor increased the LOD by 13.8-fold to femtomolar level (8.15 fM), which corresponds to a significant advance for clinical applications.

Mobility-Selected Ion Trapping and Enrichment Using Structures for Lossless Ion Manipulations

DOE PAGES

Chen, Tsung-Chi; Ibrahim, Yehia M.; Webb, Ian K.; ...

2016-01-11

The integration of ion mobility spectrometry (IMS) with mass spectrometry (MS) and the ability to trap ions in IMS-MS measurements is of great importance for performing reactions, accumulating ions, and increasing analytical measurement sensitivity. The development of Structures for Lossless Ion Manipulations (SLIM) offers the potential for ion manipulations in a more reliable and cost-effective manner, while opening opportunities for much more complex sequences of manipulations. Here, we demonstrate an ion separation and trapping module and a method based upon SLIM that consists of a linear mobility ion drift region, a switch/tee and a trapping region that allows the isolationmore » and accumulation of mobility-separated species. The operation and optimization of the SLIM switch/tee and trap are described and demonstrated for the enrichment of the low abundance ions. Lastly, we observed a linear increase in ion intensity with the number of trapping/accumulation events using the SLIM trap, illustrating its potential for enhancing the sensitivity of low abundance or targeted species.« less

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

Chen, Tsung-Chi; Ibrahim, Yehia M.; Webb, Ian K.

The integration of ion mobility spectrometry (IMS) with mass spectrometry (MS) and the ability to trap ions in IMS-MS measurements is of great importance for performing reactions, accumulating ions, and increasing analytical measurement sensitivity. The development of Structures for Lossless Ion Manipulations (SLIM) offers the potential for ion manipulations in a more reliable and cost-effective manner, while opening opportunities for much more complex sequences of manipulations. Here, we demonstrate an ion separation and trapping module and a method based upon SLIM that consists of a linear mobility ion drift region, a switch/tee and a trapping region that allows the isolationmore » and accumulation of mobility-separated species. The operation and optimization of the SLIM switch/tee and trap are described and demonstrated for the enrichment of the low abundance ions. Lastly, we observed a linear increase in ion intensity with the number of trapping/accumulation events using the SLIM trap, illustrating its potential for enhancing the sensitivity of low abundance or targeted species.« less

Effects of slow breathing rate on heart rate variability and arterial baroreflex sensitivity in essential hypertension.

PubMed

Li, Changjun; Chang, Qinghua; Zhang, Jia; Chai, Wenshu

2018-05-01

This study is to investigate the effects of slow breathing on heart rate variability (HRV) and arterial baroreflex sensitivity in essential hypertension.We studied 60 patients with essential hypertension and 60 healthy controls. All subjects underwent controlled breathing at 8 and 16 breaths per minute. Electrocardiogram, respiratory, and blood pressure signals were recorded simultaneously. We studied effects of slow breathing on heart rate, blood pressure and respiratory peak, high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio of HRV with traditional and corrected spectral analysis. Besides, we tested whether slow breathing was capable of modifying baroreflex sensitivity in hypertensive subjects.Slow breathing, compared with 16 breaths per minute, decreased the heart rate and blood pressure (all P < .05), and shifted respiratory peak toward left (P < .05). Compared to 16 breaths/minute, traditional spectral analysis showed increased LF power and LF/HF ratio, decreased HF power of HRV at 8 breaths per minute (P < .05). As breathing rate decreased, corrected spectral analysis showed increased HF power, decreased LF power, LF/HF ratio of HRV (P < .05). Compared to controls, resting baroreflex sensitivity decreased in hypertensive subjects. Slow breathing increased baroreflex sensitivity in hypertensive subjects (from 59.48 ± 6.39 to 78.93 ± 5.04 ms/mm Hg, P < .05) and controls (from 88.49 ± 6.01 to 112.91 ± 7.29 ms/mm Hg, P < .05).Slow breathing can increase HF power and decrease LF power and LF/HF ratio in essential hypertension. Besides, slow breathing increased baroreflex sensitivity in hypertensive subjects. These demonstrate slow breathing is indeed capable of shifting sympatho-vagal balance toward vagal activities and increasing baroreflex sensitivity, suggesting a safe, therapeutic approach for essential hypertension.

Development of a Fluorescent Based Immunosensor for the Serodiagnosis of Canine Leishmaniasis Combining Immunomagnetic Separation and Flow Cytometry

PubMed Central

Sousa, Susana; Cardoso, Luís; Reed, Steven G.; Reis, Alexandre B.; Martins-Filho, Olindo A.; Silvestre, Ricardo; Cordeiro da Silva, Anabela

2013-01-01

Background An accurate diagnosis is essential for the control of infectious diseases. In the search for effective and efficient tests, biosensors have increasingly been exploited for the development of new and highly sensitive diagnostic methods. Here, we describe a new fluorescent based immunosensor comprising magnetic polymer microspheres coated with recombinant antigens to improve the detection of specific antibodies generated during an infectious disease. As a challenging model, we used canine leishmaniasis due to the unsatisfactory sensitivity associated with the detection of infection in asymptomatic animals where the levels of pathogen-specific antibodies are scarce. Methodology Ni-NTA magnetic microspheres with 1,7 µm and 8,07 µm were coated with the Leishmania recombinant proteins LicTXNPx and rK39, respectively. A mixture of equal proportions of both recombinant protein-coated microspheres was used to recognize and specifically bind anti-rK39 and anti-LicTNXPx antibodies present in serum samples of infected dogs. The microspheres were recovered by magnetic separation and the percentage of fluorescent positive microspheres was quantified by flow cytometry. Principal Findings A clinical evaluation carried out with 129 dog serum samples using the antigen combination demonstrated a sensitivity of 98,8% with a specificity of 94,4%. rK39 antigen alone demonstrated a higher sensitivity for symptomatic dogs (96,9%), while LicTXNPx antigen showed a higher sensitivity for asymptomatic (94,4%). Conclusions Overall, our results demonstrated the potential of a magnetic microsphere associated flow cytometry methodology as a viable tool for highly sensitive laboratorial serodiagnosis of both clinical and subclinical forms of canine leishmaniasis. PMID:23991232

Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera

PubMed Central

Rinkevich, Frank D.; Margotta, Joseph W.; Pittman, Jean M.; Danka, Robert G.; Tarver, Matthew R.; Ottea, James A.; Healy, Kristen B.

2015-01-01

The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks) and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (<1-fold), moderate differences in pyrethroid bioassays (1.5 to 3-fold), and dramatic differences in neonicotinoid bioassays (3.4 to 33.3-fold). Synergism bioassays with piperonyl butoxide, amitraz, and coumaphos showed increased phenothrin sensitivity in all stocks and also demonstrated further physiological differences between stocks. In addition, as bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the literature. PMID:26431171

The association of noise sensitivity with music listening, training, and aptitude

PubMed Central

Kliuchko, Marina; Heinonen-Guzejev, Marja; Monacis, Lucia; Gold, Benjamin P.; Heikkilä, Kauko V.; Spinosa, Vittoria; Tervaniemi, Mari; Brattico, Elvira

2015-01-01

After intensive, long-term musical training, the auditory system of a musician is specifically tuned to perceive musical sounds. We wished to find out whether a musician's auditory system also develops increased sensitivity to any sound of everyday life, experiencing them as noise. For this purpose, an online survey, including questionnaires on noise sensitivity, musical background, and listening tests for assessing musical aptitude, was administered to 197 participants in Finland and Italy. Subjective noise sensitivity (assessed with the Weinstein's Noise Sensitivity Scale) was analyzed for associations with musicianship, musical aptitude, weekly time spent listening to music, and the importance of music in each person's life (or music importance). Subjects were divided into three groups according to their musical expertise: Nonmusicians (N = 103), amateur musicians (N = 44), and professional musicians (N = 50). The results showed that noise sensitivity did not depend on musical expertise or performance on musicality tests or the amount of active (attentive) listening to music. In contrast, it was associated with daily passive listening to music, so that individuals with higher noise sensitivity spent less time in passive (background) listening to music than those with lower sensitivity to noise. Furthermore, noise-sensitive respondents rated music as less important in their life than did individuals with lower sensitivity to noise. The results demonstrate that the special sensitivity of the auditory system derived from musical training does not lead to increased irritability from unwanted sounds. However, the disposition to tolerate contingent musical backgrounds in everyday life depends on the individual's noise sensitivity. PMID:26356378

IMRT QA: Selecting gamma criteria based on error detection sensitivity

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

Steers, Jennifer M.; Fraass, Benedick A., E-mail: benedick.fraass@cshs.org

Purpose: The gamma comparison is widely used to evaluate the agreement between measurements and treatment planning system calculations in patient-specific intensity modulated radiation therapy (IMRT) quality assurance (QA). However, recent publications have raised concerns about the lack of sensitivity when employing commonly used gamma criteria. Understanding the actual sensitivity of a wide range of different gamma criteria may allow the definition of more meaningful gamma criteria and tolerance limits in IMRT QA. We present a method that allows the quantitative determination of gamma criteria sensitivity to induced errors which can be applied to any unique combination of device, delivery technique,more » and software utilized in a specific clinic. Methods: A total of 21 DMLC IMRT QA measurements (ArcCHECK®, Sun Nuclear) were compared to QA plan calculations with induced errors. Three scenarios were studied: MU errors, multi-leaf collimator (MLC) errors, and the sensitivity of the gamma comparison to changes in penumbra width. Gamma comparisons were performed between measurements and error-induced calculations using a wide range of gamma criteria, resulting in a total of over 20 000 gamma comparisons. Gamma passing rates for each error class and case were graphed against error magnitude to create error curves in order to represent the range of missed errors in routine IMRT QA using 36 different gamma criteria. Results: This study demonstrates that systematic errors and case-specific errors can be detected by the error curve analysis. Depending on the location of the error curve peak (e.g., not centered about zero), 3%/3 mm threshold = 10% at 90% pixels passing may miss errors as large as 15% MU errors and ±1 cm random MLC errors for some cases. As the dose threshold parameter was increased for a given %Diff/distance-to-agreement (DTA) setting, error sensitivity was increased by up to a factor of two for select cases. This increased sensitivity with increasing dose threshold was consistent across all studied combinations of %Diff/DTA. Criteria such as 2%/3 mm and 3%/2 mm with a 50% threshold at 90% pixels passing are shown to be more appropriately sensitive without being overly strict. However, a broadening of the penumbra by as much as 5 mm in the beam configuration was difficult to detect with commonly used criteria, as well as with the previously mentioned criteria utilizing a threshold of 50%. Conclusions: We have introduced the error curve method, an analysis technique which allows the quantitative determination of gamma criteria sensitivity to induced errors. The application of the error curve method using DMLC IMRT plans measured on the ArcCHECK® device demonstrated that large errors can potentially be missed in IMRT QA with commonly used gamma criteria (e.g., 3%/3 mm, threshold = 10%, 90% pixels passing). Additionally, increasing the dose threshold value can offer dramatic increases in error sensitivity. This approach may allow the selection of more meaningful gamma criteria for IMRT QA and is straightforward to apply to other combinations of devices and treatment techniques.« less

Genotoxic damage in polychaetes: a study of species and cell-type sensitivities.

PubMed

Lewis, Ceri; Galloway, Tamara

2008-06-30

The marine environment is becoming increasingly contaminated by environmental pollutants with the potential to damage DNA, with marine sediments acting as a sink for many of these contaminants. Understanding genotoxic responses in sediment-dwelling marine organisms, such as polychaetes, is therefore of increasing importance. This study is an exploration of species-specific and cell-specific differences in cell sensitivities to DNA-damaging agents in polychaete worms, aimed at increasing fundamental knowledge of their responses to genotoxic damage. The sensitivities of coelomocytes from three polychaetes species of high ecological relevance, i.e. the lugworm Arenicola marina, the harbour ragworm Nereis diversicolor and the king ragworm Nereis virens to genotoxic damage are compared, and differences in sensitivities of their different coelomic cell types determined by use of the comet assay. A. marina was found to be the most sensitive to genotoxic damage induced by the direct-acting mutagen methyl methanesulfonate (MMS), and showed dose-dependent responses to MMS and the polycyclic aromatic hydrocarbon benzo(a)pyrene. Significant differences in sensitivity were also measured for the different types of coelomocyte. Eleocytes were more sensitive to induction of DNA damage than amoebocytes in both N. virens and N. diversicolor. Spermatozoa from A. marina showed significant DNA damage following in vitro exposure to MMS, but were less sensitive to DNA damage than coelomocytes. This investigation has clearly demonstrated that different cell types within the same species and different species within the polychaetes show significantly different responses to genotoxic insult. These findings are discussed in terms of the relationship between cell function and sensitivity and their implications for the use of polychaetes in environmental genotoxicity studies.

A winged helix forkhead (FOXD2) tunes sensitivity to cAMP in T lymphocytes through regulation of cAMP-dependent protein kinase RIalpha.

PubMed

Johansson, C Christian; Dahle, Maria K; Blomqvist, Sandra Rodrigo; Grønning, Line M; Aandahl, Einar M; Enerbäck, Sven; Taskén, Kjetil

2003-05-09

Forkhead/winged helix (FOX) transcription factors are essential for control of the cell cycle and metabolism. Here, we show that spleens from Mf2-/- (FOXD2-/-) mice have reduced mRNA (50%) and protein (35%) levels of the RIalpha subunit of the cAMP-dependent protein kinase. In T cells from Mf2-/- mice, reduced levels of RIalpha translates functionally into approximately 2-fold less sensitivity to cAMP-mediated inhibition of proliferation triggered through the T cell receptor-CD3 complex. In Jurkat T cells, FOXD2 overexpression increased the endogenous levels of RIalpha through induction of the RIalpha1b promoter. FOXD2 overexpression also increased the sensitivity of the promoter to cAMP. Finally, co-expression experiments demonstrated that protein kinase Balpha/Akt1 work together with FOXD2 to induce the RIalpha1b promoter (10-fold) and increase endogenous RIalpha protein levels further. Taken together, our data indicate that FOXD2 is a physiological regulator of the RIalpha1b promoter in vivo working synergistically with protein kinase B to induce cAMP-dependent protein kinase RIalpha expression, which increases cAMP sensitivity and sets the threshold for cAMP-mediated negative modulation of T cell activation.

Inhomogeneous Forcing and Transient Climate Sensitivity

NASA Technical Reports Server (NTRS)

Shindell, Drew T.

2014-01-01

Understanding climate sensitivity is critical to projecting climate change in response to a given forcing scenario. Recent analyses have suggested that transient climate sensitivity is at the low end of the present model range taking into account the reduced warming rates during the past 10-15 years during which forcing has increased markedly. In contrast, comparisons of modelled feedback processes with observations indicate that the most realistic models have higher sensitivities. Here I analyse results from recent climate modelling intercomparison projects to demonstrate that transient climate sensitivity to historical aerosols and ozone is substantially greater than the transient climate sensitivity to CO2. This enhanced sensitivity is primarily caused by more of the forcing being located at Northern Hemisphere middle to high latitudes where it triggers more rapid land responses and stronger feedbacks. I find that accounting for this enhancement largely reconciles the two sets of results, and I conclude that the lowest end of the range of transient climate response to CO2 in present models and assessments (less than 1.3 C) is very unlikely.

Investigation, development and application of optimal output feedback theory. Vol. 4: Measures of eigenvalue/eigenvector sensitivity to system parameters and unmodeled dynamics

NASA Technical Reports Server (NTRS)

Halyo, Nesim

1987-01-01

Some measures of eigenvalue and eigenvector sensitivity applicable to both continuous and discrete linear systems are developed and investigated. An infinite series representation is developed for the eigenvalues and eigenvectors of a system. The coefficients of the series are coupled, but can be obtained recursively using a nonlinear coupled vector difference equation. A new sensitivity measure is developed by considering the effects of unmodeled dynamics. It is shown that the sensitivity is high when any unmodeled eigenvalue is near a modeled eigenvalue. Using a simple example where the sensor dynamics have been neglected, it is shown that high feedback gains produce high eigenvalue/eigenvector sensitivity. The smallest singular value of the return difference is shown not to reflect eigenvalue sensitivity since it increases with the feedback gains. Using an upper bound obtained from the infinite series, a procedure to evaluate whether the sensitivity to parameter variations is within given acceptable bounds is developed and demonstrated by an example.

Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.

PubMed

Yao, Jian-Xin; Yao, Zhi-Feng; Li, Zhan-Feng; Liu, Yong-Biao

2014-01-01

The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.

Robotic crabs reveal that female fiddler crabs are sensitive to changes in male display rate.

PubMed

Mowles, Sophie L; Jennions, Michael D; Backwell, Patricia R Y

2018-01-01

Males often produce dynamic, repetitive courtship displays that can be demanding to perform and might advertise male quality to females. A key feature of demanding displays is that they can change in intensity: escalating as a male increases his signalling effort, but de-escalating as a signaller becomes fatigued. Here, we investigated whether female fiddler crabs, Uca mjoebergi , are sensitive to changes in male courtship wave rate. We performed playback experiments using robotic male crabs that had the same mean wave rate, but either escalated, de-escalated or remained constant. Females demonstrated a strong preference for escalating robots, but showed mixed responses to robots that de-escalated ('fast' to 'slow') compared to those that waved at a constant 'medium' rate. These findings demonstrate that females can discern changes in male display rate, and prefer males that escalate, but that females are also sensitive to past display rates indicative of prior vigour. © 2018 The Authors.

High speed parallel spectral-domain OCT using spectrally encoded line-field illumination

NASA Astrophysics Data System (ADS)

Lee, Kye-Sung; Hur, Hwan; Bae, Ji Yong; Kim, I. Jong; Kim, Dong Uk; Nam, Ki-Hwan; Kim, Geon-Hee; Chang, Ki Soo

2018-01-01

We report parallel spectral-domain optical coherence tomography (OCT) at 500 000 A-scan/s. This is the highest-speed spectral-domain (SD) OCT system using a single line camera. Spectrally encoded line-field scanning is proposed to increase the imaging speed in SD-OCT effectively, and the tradeoff between speed, depth range, and sensitivity is demonstrated. We show that three imaging modes of 125k, 250k, and 500k A-scan/s can be simply switched according to the sample to be imaged considering the depth range and sensitivity. To demonstrate the biological imaging performance of the high-speed imaging modes of the spectrally encoded line-field OCT system, human skin and a whole leaf were imaged at the speed of 250k and 500k A-scan/s, respectively. In addition, there is no sensitivity dependence in the B-scan direction, which is implicit in line-field parallel OCT using line focusing of a Gaussian beam with a cylindrical lens.

Effect of variable tinted spectacle lenses on visual performance in control subjects.

PubMed

Lee, Jason E; Stein, Jonathan J; Prevor, Meredith B; Seiple, William H; Holopigian, Karen; Greenstein, Vivienne C; Stenson, Susan M

2002-04-01

To evaluate quantitatively the effects of tinted spectacle lenses on visual performance in individuals without visual pathology. Twenty-five subjects were assessed by measuring contrast sensitivity with and without glare. Gray, brown, yellow, green, purple, and blue lens tints were evaluated. Measurements were repeated with each lens tint and with a clear lens, and the order was counterbalanced within and between subjects. Glare was induced with a modified brightness acuity tester. All subjects demonstrated an increase in contrast thresholds under glare conditions for all lens tints. However, purple and blue lens tints resulted in the least amount of contrast threshold increase; the yellow lens tint resulted in the largest contrast threshold increase. Purple and blue lens tints may improve contrast sensitivity in control subjects under glare conditions.

Cocaine- and amphetamine-regulated transcript peptide in the nucleus accumbens shell inhibits cocaine-induced locomotor sensitization to transient over-expression of α-Ca2+ /calmodulin-dependent protein kinase II.

PubMed

Xiong, Lixia; Meng, Qing; Sun, Xi; Lu, Xiangtong; Fu, Qiang; Peng, Qinghua; Yang, Jianhua; Oh, Ki-Wan; Hu, Zhenzhen

2018-01-04

Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter that attenuates cocaine-induced locomotor activity when injected into the nucleus accumbens (NAc). Our previous work first confirmed that the inhibitory mechanism of the CART peptide on cocaine-induced locomotor activity is related to a reduction in cocaine-enhanced phosphorylated Ca 2+ /calmodulin-dependent protein kinaseIIα (pCaMKIIα) and the enhancement of cocaine-induced D3R function. This study investigated whether CART peptide inhibited cocaine-induced locomotor activity via inhibition of interactions between pCaMKIIα and the D3 dopamine receptor (D3R). We demonstrated that lentivirus-mediated gene transfer transiently increased pCaMKIIα expression, which peaked at 10 days after microinjection into the rat NAc shell, and induced a significant increase in Ca 2+ influx along with greater behavioral sensitivity in the open field test after intraperitoneal injections of cocaine (15 mg/kg). However, western blot analysis and coimmunoprecipitation demonstrated that CART peptide treatment in lentivirus-transfected CaMKIIα-over-expressing NAc rat tissues or cells prior to cocaine administration inhibited the cocaine-induced Ca 2+ influx and attenuated the cocaine-increased pCaMKIIα expression in lentivirus-transfected CaMKIIα-over-expressing cells. CART peptide decreased the cocaine-enhanced phosphorylated cAMP response element binding protein (pCREB) expression via inhibition of the pCaMKIIα-D3R interaction, which may account for the prolonged locomotor sensitization induced by repeated cocaine treatment in lentivirus-transfected CaMKIIα-over-expressing cells. These results provide strong evidence for the inhibitory modulation of CART peptide in cocaine-induced locomotor sensitization. © 2018 International Society for Neurochemistry.

Rapid-scan Fourier-transform coherent anti-Stokes Raman scattering spectroscopy with heterodyne detection.

PubMed

Hiramatsu, Kotaro; Luo, Yizhi; Ideguchi, Takuro; Goda, Keisuke

2017-11-01

High-speed Raman spectroscopy has become increasingly important for analyzing chemical dynamics in real time. To address the need, rapid-scan Fourier-transform coherent anti-Stokes Raman scattering (FT-CARS) spectroscopy has been developed to realize broadband CARS measurements at a scan rate of more than 20,000 scans/s. However, the detection sensitivity of FT-CARS spectroscopy is inherently low due to the limited number of photons detected during each scan. In this Letter, we show our experimental demonstration of enhanced sensitivity in rapid-scan FT-CARS spectroscopy by heterodyne detection. Specifically, we implemented heterodyne detection by superposing the CARS electric field with an external local oscillator (LO) for their interference. The CARS signal was amplified by simply increasing the power of the LO without the need for increasing the incident power onto the sample. Consequently, we achieved enhancement in signal intensity and the signal-to-noise ratio by factors of 39 and 5, respectively, compared to FT-CARS spectroscopy with homodyne detection. The sensitivity-improved rapid-scan FT-CARS spectroscopy is expected to enable the sensitive real-time observation of chemical dynamics in a broad range of settings, such as combustion engines and live biological cells.

800 C Silicon Carbide (SiC) Pressure Sensors for Engine Ground Testing

NASA Technical Reports Server (NTRS)

Okojie, Robert S.

2016-01-01

MEMS-based 4H-SiC piezoresistive pressure sensors have been demonstrated at 800 C, leading to the discovery of strain sensitivity recovery with increasing temperatures above 400 C, eventually achieving up to, or near, 100 recovery of the room temperature values at 800 C. This result will allow the insertion of highly sensitive pressure sensors closer to jet, rocket, and hypersonic engine combustion chambers to improve the quantification accuracy of combustor dynamics, performance, and increase safety margin. Also, by operating at higher temperature and locating closer to the combustion chamber, reduction of the length (weight) of pressure tubes that are currently used will be achieved. This will result in reduced costlb to access space.

Reduced size first-order subsonic and supersonic aeroelastic modeling

NASA Technical Reports Server (NTRS)

Karpel, Mordechay

1990-01-01

Various aeroelastic, aeroservoelastic, dynamic-response, and sensitivity analyses are based on a time-domain first-order (state-space) formulation of the equations of motion. The formulation of this paper is based on the minimum-state (MS) aerodynamic approximation method, which yields a low number of aerodynamic augmenting states. Modifications of the MS and the physical weighting procedures make the modeling method even more attractive. The flexibility of constraint selection is increased without increasing the approximation problem size; the accuracy of dynamic residualization of high-frequency modes is improved; and the resulting model is less sensitive to parametric changes in subsequent analyses. Applications to subsonic and supersonic cases demonstrate the generality, flexibility, accuracy, and efficiency of the method.

MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells

PubMed Central

Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

2015-01-01

Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach. PMID:25949869

MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells.

PubMed

Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

2015-01-01

Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach.

AMP-activated Protein Kinase Phosphorylates Cardiac Troponin I at Ser-150 to Increase Myofilament Calcium Sensitivity and Blunt PKA-dependent Function*

PubMed Central

Nixon, Benjamin R.; Thawornkaiwong, Ariyoporn; Jin, Janel; Brundage, Elizabeth A.; Little, Sean C.; Davis, Jonathan P.; Solaro, R. John; Biesiadecki, Brandon J.

2012-01-01

AMP-activated protein kinase (AMPK) is an energy-sensing enzyme central to the regulation of metabolic homeostasis. In the heart AMPK is activated during cardiac stress-induced ATP depletion and functions to stimulate metabolic pathways that restore the AMP/ATP balance. Recently it was demonstrated that AMPK phosphorylates cardiac troponin I (cTnI) at Ser-150 in vitro. We sought to determine if the metabolic regulatory kinase AMPK phosphorylates cTnI at Ser-150 in vivo to alter cardiac contractile function directly at the level of the myofilament. Rabbit cardiac myofibrils separated by two-dimensional isoelectric focusing subjected to a Western blot with a cTnI phosphorylation-specific antibody demonstrates that cTnI is endogenously phosphorylated at Ser-150 in the heart. Treatment of myofibrils with the AMPK holoenzyme increased cTnI Ser-150 phosphorylation within the constraints of the muscle lattice. Compared with controls, cardiac fiber bundles exchanged with troponin containing cTnI pseudo-phosphorylated at Ser-150 demonstrate increased sensitivity of calcium-dependent force development, blunting of both PKA-dependent calcium desensitization, and PKA-dependent increases in length dependent activation. Thus, in addition to the defined role of AMPK as a cardiac metabolic energy gauge, these data demonstrate AMPK Ser-150 phosphorylation of cTnI directly links the regulation of cardiac metabolic demand to myofilament contractile energetics. Furthermore, the blunting effect of cTnI Ser-150 phosphorylation cross-talk can uncouple the effects of myofilament PKA-dependent phosphorylation from β-adrenergic signaling as a novel thin filament contractile regulatory signaling mechanism. PMID:22493448

Giant photocurrent enhancement by transition metal doping in quantum dot sensitized solar cells

NASA Astrophysics Data System (ADS)

Rimal, Gaurab; Pimachev, Artem K.; Yost, Andrew J.; Poudyal, Uma; Maloney, Scott; Wang, Wenyong; Chien, TeYu; Dahnovsky, Yuri; Tang, Jinke

2016-09-01

A huge enhancement in the incident photon-to-current efficiency of PbS quantum dot (QD) sensitized solar cells by manganese doping is observed. In the presence of Mn dopants with relatively small concentration (4 at. %), the photoelectric current increases by an average of 300% (up to 700%). This effect cannot be explained by the light absorption mechanism because both the experimental and theoretical absorption spectra demonstrate several times decreases in the absorption coefficient. To explain such dramatic increase in the photocurrent we propose the electron tunneling mechanism from the LUMO of the QD excited state to the Zn2SnO4 (ZTO) semiconductor photoanode. This change is due to the presence of the Mn instead of Pb atom at the QD/ZTO interface. The ab initio calculations confirm this mechanism. This work proposes an alternative route for a significant improvement of the efficiency for quantum dot sensitized solar cells.

Molecular recognition using receptor-free nanomechanical infrared spectroscopy based on a quantum cascade laser

PubMed Central

Kim, Seonghwan; Lee, Dongkyu; Liu, Xunchen; Van Neste, Charles; Jeon, Sangmin; Thundat, Thomas

2013-01-01

Speciation of complex mixtures of trace explosives presents a formidable challenge for sensors that rely on chemoselective interfaces due to the unspecific nature of weak intermolecular interactions. Nanomechanical infrared (IR) spectroscopy provides higher selectivity in molecular detection without using chemoselective interfaces by measuring the photothermal effect of adsorbed molecules on a thermally sensitive microcantilever. In addition, unlike conventional IR spectroscopy, the detection sensitivity is drastically enhanced by increasing the IR laser power, since the photothermal signal comes from the absorption of IR photons and nonradiative decay processes. By using a broadly tunable quantum cascade laser for the resonant excitation of molecules, we increased the detection sensitivity by one order of magnitude compared to the use of a conventional IR monochromator. Here, we demonstrate the successful speciation and quantification of picogram levels of ternary mixtures of similar explosives (trinitrotoluene (TNT), cyclotrimethylene trinitramine (RDX), and pentaerythritol tetranitrate (PETN)) using nanomechanical IR spectroscopy. PMID:23346368

Design and Analysis of a New Hair Sensor for Multi-Physical Signal Measurement

PubMed Central

Yang, Bo; Hu, Di; Wu, Lei

2016-01-01

A new hair sensor for multi-physical signal measurements, including acceleration, angular velocity and air flow, is presented in this paper. The entire structure consists of a hair post, a torsional frame and a resonant signal transducer. The hair post is utilized to sense and deliver the physical signals of the acceleration and the air flow rate. The physical signals are converted into frequency signals by the resonant transducer. The structure is optimized through finite element analysis. The simulation results demonstrate that the hair sensor has a frequency of 240 Hz in the first mode for the acceleration or the air flow sense, 3115 Hz in the third and fourth modes for the resonant conversion, and 3467 Hz in the fifth and sixth modes for the angular velocity transformation, respectively. All the above frequencies present in a reasonable modal distribution and are separated from interference modes. The input-output analysis of the new hair sensor demonstrates that the scale factor of the acceleration is 12.35 Hz/g, the scale factor of the angular velocity is 0.404 nm/deg/s and the sensitivity of the air flow is 1.075 Hz/(m/s)2, which verifies the multifunction sensitive characteristics of the hair sensor. Besides, the structural optimization of the hair post is used to improve the sensitivity of the air flow rate and the acceleration. The analysis results illustrate that the hollow circular hair post can increase the sensitivity of the air flow and the II-shape hair post can increase the sensitivity of the acceleration. Moreover, the thermal analysis confirms the scheme of the frequency difference for the resonant transducer can prominently eliminate the temperature influences on the measurement accuracy. The air flow analysis indicates that the surface area increase of hair post is significantly beneficial for the efficiency improvement of the signal transmission. In summary, the structure of the new hair sensor is proved to be feasible by comprehensive simulation and analysis. PMID:27399716

Seeing the Body Distorts Tactile Size Perception

ERIC Educational Resources Information Center

Longo, Matthew R.; Sadibolova, Renata

2013-01-01

Vision of the body modulates somatosensation, even when entirely non-informative about stimulation. For example, seeing the body increases tactile spatial acuity, but reduces acute pain. While previous results demonstrate that vision of the body modulates somatosensory sensitivity, it is unknown whether vision also affects metric properties of…

Use of Paired Serum Samples for Serodiagnosis of Typhoid Fever

PubMed Central

House, Deborah; Chinh, Nguyen T.; Diep, To S.; Parry, Christopher M.; Wain, John; Dougan, Gordon; White, Nicholas J.; Hien, Tran Tinh; Farrar, Jeremy J.

2005-01-01

Using an enzyme-linked immunosorbent assay we demonstrate that, in adult patients with typhoid fever, the sensitivity of a serological test based on the detection of anti-lipopolysaccharide immunoglobulin G is increased when used with paired serum samples taken 1 week apart. PMID:16145168

Measurement of the line-of-sight velocity of high-altitude barium clouds A technique

NASA Technical Reports Server (NTRS)

Mende, S. B.; Harris, S. E.

1982-01-01

It is demonstrated that for maximizing the scientific output of future ionospheric and magnetospheric ion cloud release experiments a new type of instrument is required which will measure the line-of-sight velocity of the ion cloud by the Doppler technique. A simple instrument was constructed using a 5-cm diam solid Fabry-Perot etalon coupled to a low-light-level integrating TV camera. It was demonstrated that the system has both the sensitivity and spectral resolution for detection of ion clouds and measurement of their line-of-sight Doppler velocity. The tests consisted of (1) a field experiment using a rocket barium cloud release to check sensitivity, and (2) laboratory experiments to show the spectral resolving capabilities of the system. The instrument was found to be operational if the source was brighter than approximately 1 kR, and it had a wavelength resolution much better than 0.2 A, which corresponds to approximately 12 km/sec or in the case of barium ion an acceleration potential of 100 V. The instrument is rugged and, therefore, simple to use in field experiments or on flight instruments. The sensitivity limit of the instrument can be increased by increasing the size of the etalon.

Sensitivity control of optical fiber biosensors utilizing turnaround point long period gratings with self-assembled polymer coatings

NASA Astrophysics Data System (ADS)

Gifford, Erika; Wang, Z.; Ramachandran, S.; Heflin, J. R.

2007-09-01

Ionic self-assembled multilayers (ISAMs) adsorbed on long period fiber gratings (LPGs) can serve as an inexpensive, robust, portable, biosensor platform. The ISAM technique is a layer-by-layer deposition technique that creates thin films on the nanoscale level. The combination of ISAMs with LPGs yields exceptional sensitivity of the optical fiber transmission spectrum. We have shown theoretically that the resonant wavelength shift for a thin-film coated LPG can be caused by the variation of the film's refractive index and/or the variation of the thickness of the film. We have experimentally demonstrated that the deposition of nm-thick ISAM films on LPGs induces shifts in the resonant wavelength of > 1.6 nm per nm of thin film. It has also been shown that the sensitivity of the LPG to the thickness of the ISAM film increases with increased film thickness. We have further demonstrated that ISAM-coated LPGs can function effectively as biosensors by using the biotin-streptavidin system and by using the Bacillus anthracis (Anthrax) antibody- PA (Protective Antigen) system. Experiments have been successfully performed in both air and solution, which illustrates the versatility of the biosensor. The results confirm that ISAM-LPGs yield a reusable, thermally-stable, and robust platform for designing and building efficient optical biosensors.

Neural Sensitivity to Absolute and Relative Anticipated Reward in Adolescents

PubMed Central

Vaidya, Jatin G.; Knutson, Brian; O'Leary, Daniel S.; Block, Robert I.; Magnotta, Vincent

2013-01-01

Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of absolute and relative rewards. To do so, we modified a commonly used monetary incentive delay (MID) task in order to examine brain activity to relative anticipated reward value (neural sensitivity to the value of a reward as a function of other available rewards). This design also made it possible to examine developmental differences in brain activation to absolute anticipated reward magnitude (the degree to which neural activity increases with increasing reward magnitude). While undergoing fMRI, 18 adolescents and 18 adult participants were presented with cues associated with different reward magnitudes. After the cue, participants responded to a target to win money on that trial. Presentation of cues was blocked such that two reward cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus, the relative value of the $1.00 reward varied depending on whether it was paired with a smaller or larger reward. Reflecting age differences in neural responses to relative anticipated reward (i.e., reference dependent processing), adults, but not adolescents, demonstrated greater activity to a $1 reward when it was the larger of the two available rewards. Adults also demonstrated a more linear increase in ventral striatal activity as a function of increasing absolute reward magnitude compared to adolescents. Additionally, reduced ventral striatal sensitivity to absolute anticipated reward (i.e., the difference in activity to medium versus small rewards) correlated with higher levels of trait Impulsivity. Thus, ventral striatal activity in anticipation of absolute and relative rewards develops with age. Absolute reward processing is also linked to individual differences in Impulsivity. PMID:23544046

Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice.

PubMed

Piccinelli, Ana Claudia; Morato, Priscila Neder; Dos Santos Barbosa, Marcelo; Croda, Julio; Sampson, Jared; Kong, Xiangpeng; Konkiewitz, Elisabete Castelon; Ziff, Edward B; Amaya-Farfan, Jaime; Kassuya, Cândida Aparecida Leite

2017-04-01

We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Male Swiss mice received gp120, IL-1β or TNF-α intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification. Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1β and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1β-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1β injection. These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1β and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1β application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1β emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences. Copyright © 2016. Published by Elsevier Inc.

Reflective terahertz (THz) imaging: system calibration using hydration phantoms

NASA Astrophysics Data System (ADS)

Bajwa, Neha; Garritano, James; Lee, Yoon Kyung; Tewari, Priyamvada; Sung, Shijun; Maccabi, Ashkan; Nowroozi, Bryan; Babakhanian, Meghedi; Sanghvi, Sajan; Singh, Rahul; Grundfest, Warren; Taylor, Zachary

2013-02-01

Terahertz (THz) hydration sensing continues to gain traction in the medical imaging community due to its unparalleled sensitivity to tissue water content. Rapid and accurate detection of fluid shifts following induction of thermal skin burns as well as remote corneal hydration sensing have been previously demonstrated in vivo using reflective, pulsed THz imaging. The hydration contrast sensing capabilities of this technology were recently confirmed in a parallel 7 Tesla Magnetic Resonance (MR) imaging study, in which burn areas are associated with increases in local mobile water content. Successful clinical translation of THz sensing, however, still requires quantitative assessments of system performance measurements, specifically hydration concentration sensitivity, with tissue substitutes. This research aims to calibrate the sensitivity of a novel, reflective THz system to tissue water content through the use of hydration phantoms for quantitative comparisons of THz hydration imagery.Gelatin phantoms were identified as an appropriate tissue-mimicking model for reflective THz applications, and gel composition, comprising mixtures of water and protein, was varied between 83% to 95% hydration, a physiologically relevant range. A comparison of four series of gelatin phantom studies demonstrated a positive linear relationship between THz reflectivity and water concentration, with statistically significant hydration sensitivities (p < .01) ranging between 0.0209 - 0.038% (reflectivity: %hydration). The THz-phantom interaction is simulated with a three-layer model using the Transfer Matrix Method with agreement in hydration trends. Having demonstrated the ability to accurately and noninvasively measure water content in tissue equivalent targets with high sensitivity, reflective THz imaging is explored as a potential tool for early detection and intervention of corneal pathologies.

Stochastic sensitivity of a bistable energy model for visual perception

NASA Astrophysics Data System (ADS)

Pisarchik, Alexander N.; Bashkirtseva, Irina; Ryashko, Lev

2017-01-01

Modern trends in physiology, psychology and cognitive neuroscience suggest that noise is an essential component of brain functionality and self-organization. With adequate noise the brain as a complex dynamical system can easily access different ordered states and improve signal detection for decision-making by preventing deadlocks. Using a stochastic sensitivity function approach, we analyze how sensitive equilibrium points are to Gaussian noise in a bistable energy model often used for qualitative description of visual perception. The probability distribution of noise-induced transitions between two coexisting percepts is calculated at different noise intensity and system stability. Stochastic squeezing of the hysteresis range and its transition from positive (bistable regime) to negative (intermittency regime) are demonstrated as the noise intensity increases. The hysteresis is more sensitive to noise in the system with higher stability.

ACOEM practice guidelines: opioids and safety-sensitive work.

PubMed

Hegmann, Kurt T; Weiss, Michael S; Bowden, Kirk; Branco, Fernando; DuBrueler, Kimberly; Els, Charl; Mandel, Steven; McKinney, David W; Miguel, Rafael; Mueller, Kathryn L; Nadig, Robert J; Schaffer, Michael I; Studt, Larry; Talmage, James B; Travis, Russell L; Winters, Thomas; Thiese, Matthew S; Harris, Jeffrey S

2014-07-01

ACOEM has updated the treatment guidelines concerning opioids. This report highlights the safety-sensitive work recommendation that has been developed. Comprehensive literature reviews were accomplished with article abstraction, critiquing, grading, evidence table compilation, and guideline finalization by a multidisciplinary expert panel to develop evidence-based guidance. A total of 12 moderate-quality studies were identified to address motor vehicle crash risk, and none regarding other work among opioid-using patients. Acute or chronic opioid use is not recommended for patients who perform safety-sensitive jobs. These jobs include operating motor vehicles, other modes of transportation, forklift driving, overhead crane operation, heavy equipment operation and tasks involving high levels of cognitive function and judgment. Quality evidence consistently demonstrates increased risk of vehicle crashes and is recommended as the surrogate for other safety-sensitive work tasks.

Exogenous attention enhances 2nd-order contrast sensitivity

PubMed Central

Barbot, Antoine; Landy, Michael S.; Carrasco, Marisa

2011-01-01

Natural scenes contain a rich variety of contours that the visual system extracts to segregrate the retinal image into perceptually coherent regions. Covert spatial attention helps extract contours by enhancing contrast sensitivity for 1st-order, luminance-defined patterns at attended locations, while reducing sensitivity at unattended locations, relative to neutral attention allocation. However, humans are also sensitive to 2nd-order patterns such as spatial variations of texture, which are predominant in natural scenes and cannot be detected by linear mechanisms. We assess whether and how exogenous attention—the involuntary and transient capture of spatial attention—affects the contrast sensitivity of channels sensitive to 2nd-order, texture-defined patterns. Using 2nd-order, texture-defined stimuli, we demonstrate that exogenous attention increases 2nd-order contrast sensitivity at the attended location, while decreasing it at unattended locations, relative to a neutral condition. By manipulating both 1st- and 2nd-order spatial frequency, we find that the effects of attention depend both on 2nd-order spatial frequency of the stimulus and the observer’s 2nd-order spatial resolution at the target location. At parafoveal locations, attention enhances 2nd-order contrast sensitivity to high, but not to low 2nd-order spatial frequencies; at peripheral locations attention also enhances sensitivity to low 2nd-order spatial frequencies. Control experiments rule out the possibility that these effects might be due to an increase in contrast sensitivity at the 1st-order stage of visual processing. Thus, exogenous attention affects 2nd-order contrast sensitivity at both attended and unattended locations. PMID:21356228

Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport

PubMed Central

Velez, Juliana; Pan, Rongqing; Lee, Jason T.C.; Enciso, Leonardo; Suarez, Marta; Duque, Jorge Eduardo; Jaramillo, Daniel; Lopez, Catalina; Morales, Ludis; Bornmann, William; Konopleva, Marina; Krystal, Gerald; Andreeff, Michael; Samudio, Ismael

2016-01-01

Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax. PMID:27283492

Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport.

PubMed

Velez, Juliana; Pan, Rongqing; Lee, Jason T C; Enciso, Leonardo; Suarez, Marta; Duque, Jorge Eduardo; Jaramillo, Daniel; Lopez, Catalina; Morales, Ludis; Bornmann, William; Konopleva, Marina; Krystal, Gerald; Andreeff, Michael; Samudio, Ismael

2016-08-09

Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax.

Investigation of Ion Transmission Effects on Intact Protein Quantification in a Triple Quadrupole Mass Spectrometer

NASA Astrophysics Data System (ADS)

Wang, Evelyn H.; Appulage, Dananjaya Kalu; McAllister, Erin A.; Schug, Kevin A.

2017-09-01

Recently, direct intact protein quantitation using triple quadrupole mass spectrometry (QqQ-MS) and multiple reaction monitoring (MRM) was demonstrated (J. Am. Soc. Mass Spectrom. 27, 886-896 (2016)). Even though QqQ-MS is known to provide extraordinary detection sensitivity for quantitative analysis, we found that intact proteins exhibited a less than 5% ion transmission from the first quadrupole to the third quadrupole mass analyzer in the presence of zero collision energy (ZCE). With the goal to enhance intact protein quantitation sensitivity, ion scattering effects, proton transfer effects, and mass filter resolution widths were examined for their contributions to the lost signal. Protein standards myoglobin and ubiquitin along with small molecules reserpine and vancomycin were analyzed together with various collision induced dissociation (CID) gases (N2, He, and Ar) at different gas pressures. Mass resolution settings played a significant role in reducing ion transmission signal. By narrowing the mass resolution window by 0.35 m/z on each side, roughly 75%-90% of the ion signal was lost. The multiply charged proteins experienced additional proton transfer effects, corresponding to 10-fold signal reduction. A study of increased sensitivity of the method was also conducted with various MRM summation techniques. Although the degree of enhancement was analyte-dependent, an up to 17-fold increase in sensitivity was observed for ubiquitin using a summation of multiple MRM transitions. Biological matrix, human urine, and equine plasma were spiked with proteins to demonstrate the specificity of the method. This study provides additional insight into optimizing the use and sensitivity of QqQ-MS for intact protein quantification. [Figure not available: see fulltext.

Poly(ADP-ribose) Polymerase Inhibitors Sensitize Cancer Cells to Death Receptor-mediated Apoptosis by Enhancing Death Receptor Expression*

PubMed Central

Meng, X. Wei; Koh, Brian D.; Zhang, Jin-San; Flatten, Karen S.; Schneider, Paula A.; Billadeau, Daniel D.; Hess, Allan D.; Smith, B. Douglas; Karp, Judith E.; Kaufmann, Scott H.

2014-01-01

Recombinant human tumor necrosis factor-α-related apoptosis inducing ligand (TRAIL), agonistic monoclonal antibodies to TRAIL receptors, and small molecule TRAIL receptor agonists are in various stages of preclinical and early phase clinical testing as potential anticancer drugs. Accordingly, there is substantial interest in understanding factors that affect sensitivity to these agents. In the present study we observed that the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and veliparib sensitize the myeloid leukemia cell lines ML-1 and K562, the ovarian cancer line PEO1, non-small cell lung cancer line A549, and a majority of clinical AML isolates, but not normal marrow, to TRAIL. Further analysis demonstrated that PARP inhibitor treatment results in activation of the FAS and TNFRSF10B (death receptor 5 (DR5)) promoters, increased Fas and DR5 mRNA, and elevated cell surface expression of these receptors in sensitized cells. Chromatin immunoprecipitation demonstrated enhanced binding of the transcription factor Sp1 to the TNFRSF10B promoter in the presence of PARP inhibitor. Knockdown of PARP1 or PARP2 (but not PARP3 and PARP4) not only increased expression of Fas and DR5 at the mRNA and protein level, but also recapitulated the sensitizing effects of the PARP inhibition. Conversely, Sp1 knockdown diminished the PARP inhibitor effects. In view of the fact that TRAIL is part of the armamentarium of natural killer cells, these observations identify a new facet of PARP inhibitor action while simultaneously providing the mechanistic underpinnings of a novel therapeutic combination that warrants further investigation. PMID:24895135

The Positive Inotropic Effect of Pyruvate Involves an Increase in Myofilament Calcium Sensitivity

PubMed Central

Torres, Carlos A. A.; Varian, Kenneth D.; Canan, Cynthia H.; Davis, Jonathan P.; Janssen, Paul M. L.

2013-01-01

Pyruvate is a metabolic fuel that is a potent inotropic agent. Despite its unique inotropic and antioxidant properties, the molecular mechanism of its inotropic mechanism is still largely unknown. To examine the inotropic effect of pyruvate in parallel with intracellular calcium handling under near physiological conditions, we measured pH, myofilament calcium sensitivity, developed force, and calcium transients in ultra thin rabbit heart trabeculae at 37 °C loaded iontophoretically with the calcium indicator bis-fura-2. By contrasting conditions of control versus sarcoplasmic reticulum block (with either cyclopiazonic acid and ryanodine or with thapsigargin) we were able to characterize and isolate the effects of pyruvate on sarcoplasmic reticulum calcium handling and developed force. A potassium contracture technique was subsequently utilized to assess the force-calcium relationship and thus the myofilament calcium sensitivity. Pyruvate consistently increased developed force whether or not the sarcoplasmic reticulum was blocked (16.8±3.5 to 24.5±5.1 vs. 6.9±2.6 to 12.5±4.4 mN/mm2, non-blocked vs. blocked sarcoplasmic reticulum respectively, p<0.001, n = 9). Furthermore, the sensitizing effect of pyruvate on the myofilaments was demonstrated by potassium contractures (EC50 at baseline versus 20 minutes of pyruvate infusion (peak force development) was 701±94 vs. 445±65 nM, p<0.01, n = 6). This study is the first to demonstrate that a leftward shift in myofilament calcium sensitivity is an important mediator of the inotropic effect of pyruvate. This finding can have important implications for future development of therapeutic strategies in the management of heart failure. PMID:23691074

Bronchial inflammation induced PKCζ over-expression: involvement in mechanical properties of airway smooth muscle.

PubMed

Morin, Caroline; Fortin, Samuel; Rousseau, Eric

2012-02-01

Protein kinase C variants (PKCs) have been involved in the control of airway smooth muscle (ASM) tone, and abnormalities in PKC-dependent signaling have been associated with respiratory diseases such as asthma. In this study, the role of atypical PKCζ in airway hyperresponsiveness was investigated, using an in-vitro model of TNFα-treated human bronchi and an in vivo guinea pig model of chronic asthma. Our results demonstrated that PKCζ-specific inhibition produced a significant increase in isoproterenol sensitivity in TNFα-treated bronchi and ovalbumin (OVA)-sensitized guinea pig bronchi. The role of epoxy-eicosanoids, known to exert anti-inflammatory effects in lung, on PKCζ expression and activity in these models was evaluated. An enhanced PKCζ protein expression was delineated in TNFα-treated bronchi when compared with control (untreated) and epoxy-eicosanoid-treated bronchi. Measurements of Ca(2+) sensitivity, performed in TNFα-treated bronchi, demonstrated that treatment with myristoylated (Myr) PKCζ peptide inhibitor resulted in significant reductions of pCa-induced tension. Epoxy-eicosanoid treatments had similar effects on Ca(2+) sensitivity in TNFα-treated bronchi. In control and epoxy-eicosanoid-treated bronchi, the phosphorylated forms of p38MAPK and CPI-17 were significantly decreased compared with the TNFα-treated bronchi. An enhanced expression of PKCζ was ascertained in our in-vivo model of allergic asthma. Hence an increased Ca(2+) sensitivity could be explained by the phosphorylation of p38-MAPK, which in turn leads to phosphorylation and activation of the CPI-17 regulatory protein. This process was reversed upon treatment with the Myr-PKCζ-peptide inhibitor. The present data provide relevant evidence regarding the role of PKCζ in human and rodent models of airways inflammation.

Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics

PubMed Central

Cideciyan, Artur V.; Aleman, Tomas S.; Boye, Sanford L.; Schwartz, Sharon B.; Kaushal, Shalesh; Roman, Alejandro J.; Pang, Ji-jing; Sumaroka, Alexander; Windsor, Elizabeth A. M.; Wilson, James M.; Flotte, Terence R.; Fishman, Gerald A.; Heon, Elise; Stone, Edwin M.; Byrne, Barry J.; Jacobson, Samuel G.; Hauswirth, William W.

2008-01-01

The RPE65 gene encodes the isomerase of the retinoid cycle, the enzymatic pathway that underlies mammalian vision. Mutations in RPE65 disrupt the retinoid cycle and cause a congenital human blindness known as Leber congenital amaurosis (LCA). We used adeno-associated virus-2-based RPE65 gene replacement therapy to treat three young adults with RPE65-LCA and measured their vision before and up to 90 days after the intervention. All three patients showed a statistically significant increase in visual sensitivity at 30 days after treatment localized to retinal areas that had received the vector. There were no changes in the effect between 30 and 90 days. Both cone- and rod-photoreceptor-based vision could be demonstrated in treated areas. For cones, there were increases of up to 1.7 log units (i.e., 50 fold); and for rods, there were gains of up to 4.8 log units (i.e., 63,000 fold). To assess what fraction of full vision potential was restored by gene therapy, we related the degree of light sensitivity to the level of remaining photoreceptors within the treatment area. We found that the intervention could overcome nearly all of the loss of light sensitivity resulting from the biochemical blockade. However, this reconstituted retinoid cycle was not completely normal. Resensitization kinetics of the newly treated rods were remarkably slow and required 8 h or more for the attainment of full sensitivity, compared with <1 h in normal eyes. Cone-sensitivity recovery time was rapid. These results demonstrate dramatic, albeit imperfect, recovery of rod- and cone-photoreceptor-based vision after RPE65 gene therapy. PMID:18809924

Quantitation of MRI sensitivity to quasi-monodisperse microbubble contrast agents for spatially resolved manometry.

PubMed

Bencsik, Martin; Al-Rwaili, Amgad; Morris, Robert; Fairhurst, David J; Mundell, Victoria; Cave, Gareth; McKendry, Jonathan; Evans, Stephen

2013-11-01

The direct in-vivo measurement of fluid pressure cannot be achieved with MRI unless it is done with the contribution of a contrast agent. No such contrast agents are currently available commercially, whilst those demonstrated previously only produced qualitative results due to their broad size distribution. Our aim is to quantitate then model the MR sensitivity to the presence of quasi-monodisperse microbubble populations. Lipid stabilised microbubble populations with mean radius 1.2 ± 0.8 μm have been produced by mechanical agitation. Contrast agents with increasing volume fraction of bubbles up to 4% were formed and the contribution the bubbles bring to the relaxation rate was quantitated. A periodic pressure change was also continuously applied to the same contrast agent, until MR signal changes were only due to bubble radius change and not due to a change in bubble density. The MR data compared favourably with the prediction of an improved numerical simulation. An excellent MR sensitivity of 23 % bar(-1) has been demonstrated. This work opens up the possibility of generating microbubble preparations tailored to specific applications with optimised MR sensitivity, in particular MRI based in-vivo manometry. Copyright © 2012 Wiley Periodicals, Inc.

Pressure-sensitive strain sensor based on a single percolated Ag nanowire layer embedded in colorless polyimide

NASA Astrophysics Data System (ADS)

Lee, Chan-Jae; Jun, Sungwoo; Ju, Byeong-Kwon; Kim, Jong-Woong

2017-06-01

This paper presents the fabrication of an elastomer-free, transparent, pressure-sensitive strain sensor consisting of a specially designed silver nanowire (AgNW) pattern and colorless polyimide (cPI). A percolated AgNW network was patterned with a simple tandem compound circuit, which was then embedded in the surface of the cPI via inverted layer processing. The resulting film-type sensor was highly transparent ( 93.5% transmittance at 550 nm) and mechanically stable (capable of resisting 10000 cycles of bending to a 500 μm radius of curvature). We demonstrated that a thin, transparent, and mechanically stable electrode can be produced using a combination of AgNWs and cPI, and used to produce a system sensitive to pressure-induced bending. The capacitance of the AgNW tandem compound electrode pattern grew via fringing, which increased with the pressure-induced bending applied to the surface of the sensor. The sensitivity was four times higher than that of an elastomeric pressure sensor made with the same design. Finally, we demonstrated a skin-like pressure sensor attached to the inside wrist of a human arm.

A Probabilistic Design Method Applied to Smart Composite Structures

NASA Technical Reports Server (NTRS)

Shiao, Michael C.; Chamis, Christos C.

1995-01-01

A probabilistic design method is described and demonstrated using a smart composite wing. Probabilistic structural design incorporates naturally occurring uncertainties including those in constituent (fiber/matrix) material properties, fabrication variables, structure geometry and control-related parameters. Probabilistic sensitivity factors are computed to identify those parameters that have a great influence on a specific structural reliability. Two performance criteria are used to demonstrate this design methodology. The first criterion requires that the actuated angle at the wing tip be bounded by upper and lower limits at a specified reliability. The second criterion requires that the probability of ply damage due to random impact load be smaller than an assigned value. When the relationship between reliability improvement and the sensitivity factors is assessed, the results show that a reduction in the scatter of the random variable with the largest sensitivity factor (absolute value) provides the lowest failure probability. An increase in the mean of the random variable with a negative sensitivity factor will reduce the failure probability. Therefore, the design can be improved by controlling or selecting distribution parameters associated with random variables. This can be implemented during the manufacturing process to obtain maximum benefit with minimum alterations.

Therapeutic response to metformin in an underweight patient with polycystic ovarian syndrome.

PubMed

Al-Ozairi, Ebaa; Quinton, Richard; Advani, Andrew

2008-10-01

To report a case where insulin sensitization restored menses in an underweight woman with polycystic ovarian syndrome (PCOS). Case report. Tertiary care center. A 19-year-old woman with a body mass index of 16.9 kg/m(2), severe hirsutism, and oligomenorrhea. Insulin sensitization with metformin. Impact of metformin therapy on menstrual cycle and serum T and fasting insulin levels. Metformin, without weight loss or increased physical activity, resulted in restoration of menstrual cycle, reduction in serum T, and improvement in insulin resistance (IR). This case highlights the contribution of PCOS-related IR, distinct from visceral adiposity, and demonstrates the effectiveness of pharmacological insulin-sensitization independent of weight loss or lifestyle adjustments.

The temperature and tension characteristics of the FBGs embedded in the polythene sheath of an optical cable

NASA Astrophysics Data System (ADS)

Chen, Guanghui; Zhao, Ming; Sha, Jianbo; Zhang, Jun; Wu, Bingyan; Lin, Chen; Zhang, Mingliang; Gao, Kan

2015-10-01

The five of FBG were embedded in the PE sheath of a tether optical cable, which has about 18mm diameter and 7000mm length. The temperature and tension characteristics of the FBGs embedded in the polythene (PE) sheath had been demonstrated quantitatively. The Bragg wavelength of the embedded FBG shift linearly with the change of pulling force loaded on the tether optical cable and its tension sensitivity is about 3.75 pm/kg. The results of temperature experiment suggest the embedded FBG have been sensitized by PE material, so that its temperature sensitivity increase from 9.37pm/°C to about 12.51pm/°C.

Effects of a Teacher Professional Development Intervention on Peer Relationships in Secondary Classrooms

ERIC Educational Resources Information Center

Mikami, Amori Yee; Gregory, Anne; Allen, Joseph P.; Pianta, Robert C.; Lun, Janetta

2011-01-01

We investigated the effects of My Teaching Partner-Secondary (MTP-S), a teacher professional development intervention, on students' peer relationships in middle and high school classrooms. MTP-S targets increasing teachers' positive interactions with students and sensitive instructional practices and has demonstrated improvements in students'…

Acute and delayed effects of intermittant ozone on cardiovascular and thermoregulatory responses of young and aged rats

EPA Science Inventory

Ozone (03) is associated with cardiovascular and respiratory diseases. The aged population is considered to be more sensitive to air pollutants but relatively few studies have demonstrated increased susceptibility in animal models of aging. To study the acute and delayed physiolo...

Improvement of insulin sensitivity in response to exercise training in type 2 diabetes mellitus is associated with vascular endothelial growth factor A expression.

PubMed

Wagner, Henrik; Fischer, Helene; Degerblad, Marie; Alvarsson, Michael; Gustafsson, Thomas

2016-09-01

Insulin sensitivity changes in response to exercise training demonstrate a large variation. Vascular endothelial growth factor A could promote increased insulin sensitivity through angiogenesis. We investigated associations between changes in expression of key genes and insulin sensitivity, aerobic capacity and glycaemic control following exercise training in diabetes mellitus type 2. Subjects with diabetes mellitus type 2 underwent 12 weeks of structured exercise. Euglycaemic clamp, exercise test and HbA1c were performed. Muscle biopsies were obtained for mRNA expression. A total of 16 subjects completed the study. Change in vascular endothelial growth factor A expression was positively associated with an increase in insulin sensitivity (p = 0.004) and with a decrease in HbA1c (p = 0.034). Vascular endothelial growth factor A receptor-1 expression showed similar associations. The variation in physical adaptation to exercise training in diabetes mellitus type 2 was associated with changes in expression of vascular endothelial growth factor A in muscle. This difference in induced gene expression could contribute to the variation in exercise training effects on insulin sensitivity. Measures of capillary blood flow need to be assessed in future studies. © The Author(s) 2016.

Sensitivity to binaural timing in bilateral cochlear implant users.

PubMed

van Hoesel, Richard J M

2007-04-01

Various measures of binaural timing sensitivity were made in three bilateral cochlear implant users, who had demonstrated moderate-to-good interaural time delay (ITD) sensitivity at 100 pulses-per-second (pps). Overall, ITD thresholds increased at higher pulse rates, lower levels, and shorter durations, although intersubject differences were evident. Monaural rate-discrimination thresholds, using the same stimulation parameters, showed more substantial elevation than ITDs with increased rate. ITD sensitivity with 6000 pps stimuli, amplitude-modulated at 100 Hz, was similar to that with unmodulated pulse trains at 100 pps, but at 200 and 300 Hz performance was poorer than with unmodulated signals. Measures of sensitivity to binaural beats with unmodulated pulse-trains showed that all three subjects could use time-varying ITD cues at 100 pps, but not 300 pps, even though static ITD sensitivity was relatively unaffected over that range. The difference between static and dynamic ITD thresholds is discussed in terms of relative contributions from initial and later arriving cues, which was further examined in an experiment using two-pulse stimuli as a function of interpulse separation. In agreement with the binaural-beat data, findings from that experiment showed poor discrimination of ITDs on the second pulse when the interval between pulses was reduced to a few milliseconds.

Palmitoylethanolamide Supplementation during Sensitization Prevents Airway Allergic Symptoms in the Mouse

PubMed Central

Roviezzo, Fiorentina; Rossi, Antonietta; Caiazzo, Elisabetta; Orlando, Pierangelo; Riemma, Maria A.; Iacono, Valentina M.; Guarino, Andrea; Ialenti, Armando; Cicala, Carla; Peritore, Alessio; Capasso, Raffaele; Di Marzo, Vincenzo; Izzo, Angelo A.

2017-01-01

One important risk factor for the development of asthma is allergen sensitization. Recent increasing evidence suggests a prominent role of mast cells in asthma pathophysiology. Since Palmitoylethanolamide (PEA), an endogenous lipid mediator chemically related to – and co-released with- the endocannabinoid anandamide, behaves as a local autacoid down-regulator of mast cell activation and inflammation, we explored the possible contribution of PEA in allergic sensitization, by using ovalbumin (OVA) as sensitizing agent in the mouse. PEA levels were dramatically reduced in the bronchi of OVA-treated animals. This effect was coupled to a significant up-regulation of CB2 and GPR55 receptors, two of the proposed molecular PEA targets, in bronchi harvested from allergen-sensitized mice. PEA supplementation (10 mg/kg, 15 min before each allergen exposure) prevented OVA-induced bronchial hyperreactivity, but it did not affect IgE plasma increase. On the other hand, PEA abrogated allergen-induced cell recruitment as well as pulmonary inflammation. Evaluation of pulmonary sections evidenced a significant inhibitory action of PEA on pulmonary mast cell recruitment and degranulation, an effect coupled to a reduction of leukotriene C4 production. These findings demonstrate that allergen sensitization negatively affects PEA bronchial levels and suggest that its supplementation has the potential to prevent the development of asthma-like features. PMID:29311913

High sensitivity to short wavelengths in a lizard and implications for understanding the evolution of visual systems in lizards

PubMed Central

Fleishman, Leo J.; Loew, Ellis R.; Whiting, Martin J.

2011-01-01

Progress in developing animal communication theory is frequently constrained by a poor understanding of sensory systems. For example, while lizards have been the focus of numerous studies in visual signalling, we only have data on the spectral sensitivities of a few species clustered in two major clades (Iguania and Gekkota). Using electroretinography and microspectrophotometry, we studied the visual system of the cordylid lizard Platysaurus broadleyi because it represents an unstudied clade (Scinciformata) with respect to visual systems and because UV signals feature prominently in its social behaviour. The retina possessed four classes of single and one class of double cones. Sensitivity in the ultraviolet region (UV) was approximately three times higher than previously reported for other lizards. We found more colourless oil droplets (associated with UV-sensitive (UVS) and short wavelength-sensitive (SWS) photoreceptors), suggesting that the increased sensitivity was owing to the presence of more UVS photoreceptors. Using the Vorobyev–Osorio colour discrimination model, we demonstrated that an increase in the number of UVS photoreceptors significantly enhances a lizard's ability to discriminate conspecific male throat colours. Visual systems in diurnal lizards appear to be broadly conserved, but data from additional clades are needed to confirm this. PMID:21389031

Obesity Increases Sensitivity to Endotoxin Liver Injury: Implications for the Pathogenesis of Steatohepatitis

NASA Astrophysics Data System (ADS)

Yang, Shi Qi; Zhi Lin, Hui; Lane, M. Daniel; Clemens, Mark; Diehl, Anna Mae

1997-03-01

Genetically obese fatty/fatty rats and obese/obese mice exhibit increased sensitivity to endotoxin hepatotoxicity, quickly developing steatohepatitis after exposure to low doses of lipopolysaccharide (LPS). Among obese animals, females are more sensitive to endotoxin liver injury than males. LPS induction of tumor necrosis factor α (TNFα ), the proven affecter of endotoxin liver injury, is no greater in the livers, white adipose tissues, or sera of obese animals than in those of lean controls. Indeed, the lowest serum concentrations of TNF occur in female obese rodents, which exhibit the most endotoxin-induced liver injury. Several cytokines that modulate the biological activity of TNF are regulated abnormally in the livers of obese animals. After exposure to LPS, mRNA of interferon γ , which sensitizes hepatocytes to TNF toxicity, is overexpressed, and mRNA levels of interleukin 10, a TNF inhibitor, are decreased. The phagocytic activity of liver macrophages and the hepatic expression of a gene encoding a macrophage-specific receptor are also decreased in obesity. This new animal model of obesity-associated liver disease demonstrates that hepatic macrophage dysfunction occurs in obesity and suggests that this might promote steatohepatitis by sensitizing hepatocytes to endotoxin.

Estimating the Triple-Point Isotope Effect and the Corresponding Uncertainties for Cryogenic Fixed Points

NASA Astrophysics Data System (ADS)

Tew, W. L.

2008-02-01

The sensitivities of melting temperatures to isotopic variations in monatomic and diatomic atmospheric gases using both theoretical and semi-empirical methods are estimated. The current state of knowledge of the vapor-pressure isotope effects (VPIE) and triple-point isotope effects (TPIE) is briefly summarized for the noble gases (except He), and for selected diatomic molecules including oxygen. An approximate expression is derived to estimate the relative shift in the melting temperature with isotopic substitution. In general, the magnitude of the effects diminishes with increasing molecular mass and increasing temperature. Knowledge of the VPIE, molar volumes, and heat of fusion are sufficient to estimate the temperature shift or isotopic sensitivity coefficient via the derived expression. The usefulness of this approach is demonstrated in the estimation of isotopic sensitivities and uncertainties for triple points of xenon and molecular oxygen for which few documented estimates were previously available. The calculated sensitivities from this study are considerably higher than previous estimates for Xe, and lower than other estimates in the case of oxygen. In both these cases, the predicted sensitivities are small and the resulting variations in triple point temperatures due to mass fractionation effects are less than 20 μK.

Sensitivity of water resources in the Delaware River basin to climate variability and change

USGS Publications Warehouse

Ayers, Mark A.; Wolock, David M.; McCabe, Gregory J.; Hay, Lauren E.; Tasker, Gary D.

1994-01-01

Because of the greenhouse effect, projected increases in atmospheric carbon dioxide levels might cause global warming, which in turn could result in changes in precipitation patterns and evapotranspiration and in increases in sea level. This report describes the greenhouse effect; discusses the problems and uncertainties associated with the detection, prediction, and effects of climate change; and presents the results of sensitivity analyses of how climate change might affect water resources in the Delaware River basin. Sensitivity analyses suggest that potentially serious shortfalls of certain water resources in the basin could result if some scenarios for climate change come true . The results of model simulations of the basin streamflow demonstrate the difficulty in distinguishing the effects that climate change versus natural climate variability have on streamflow and water supply . The future direction of basin changes in most water resources, furthermore, cannot be precisely determined because of uncertainty in current projections of regional temperature and precipitation . This large uncertainty indicates that, for resource planning, information defining the sensitivities of water resources to a range of climate change is most relevant . The sensitivity analyses could be useful in developing contingency plans for evaluating and responding to changes, should they occur.

Compositional effects on the ignition of FACE gasolines [Compositional effects on the ignition of FACE gasoline fuels: experiments, surrogate fuel formulation, and chemical kinetic modeling

DOE PAGES

Sarathy, S. Mani; Kukkadapu, Goutham; Mehl, Marco; ...

2016-05-08

As regulatory measures for improved fuel economy and decreased emissions are pushing gasoline engine combustion technologies towards extreme conditions (i.e., boosted and intercooled intake with exhaust gas recirculation), fuel ignition characteristics become increasingly important for enabling stable operation. Here, this study explores the effects of chemical composition on the fundamental ignition behavior of gasoline fuels. Two well-characterized, high-octane, non-oxygenated FACE (Fuels for Advanced Combustion Engines) gasolines, FACE F and FACE G, having similar antiknock indices but different octane sensitivities and chemical compositions are studied. Ignition experiments were conducted in shock tubes and a rapid compression machine (RCM) at nominal pressuresmore » of 20 and 40 atm, equivalence ratios of 0.5 and 1.0, and temperatures ranging from 650 to 1270 K. Results at temperatures above 900 K indicate that ignition delay time is similar for these fuels. However, RCM measurements below 900 K demonstrate a stronger negative temperature coefficient behavior for FACE F gasoline having lower octane sensitivity. In addition, RCM pressure profiles under two-stage ignition conditions illustrate that the magnitude of low-temperature heat release (LTHR) increases with decreasing fuel octane sensitivity. However, intermediate-temperature heat release is shown to increase as fuel octane sensitivity increases. Various surrogate fuel mixtures were formulated to conduct chemical kinetic modeling, and complex multicomponent surrogate mixtures were shown to reproduce experimentally observed trends better than simpler two- and three-component mixtures composed of n-heptane, iso-octane, and toluene. Measurements in a Cooperative Fuels Research (CFR) engine demonstrated that the multicomponent surrogates accurately captured the antiknock quality of the FACE gasolines. Simulations were performed using multicomponent surrogates for FACE F and G to reveal the underlying chemical kinetics linking fuel composition with ignition characteristics. Finally, a key discovery of this work is the kinetic coupling between aromatics and naphthenes, which affects the radical pool population and thereby controls ignition.« less

Compositional effects on the ignition of FACE gasolines [Compositional effects on the ignition of FACE gasoline fuels: experiments, surrogate fuel formulation, and chemical kinetic modeling

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

Sarathy, S. Mani; Kukkadapu, Goutham; Mehl, Marco

As regulatory measures for improved fuel economy and decreased emissions are pushing gasoline engine combustion technologies towards extreme conditions (i.e., boosted and intercooled intake with exhaust gas recirculation), fuel ignition characteristics become increasingly important for enabling stable operation. Here, this study explores the effects of chemical composition on the fundamental ignition behavior of gasoline fuels. Two well-characterized, high-octane, non-oxygenated FACE (Fuels for Advanced Combustion Engines) gasolines, FACE F and FACE G, having similar antiknock indices but different octane sensitivities and chemical compositions are studied. Ignition experiments were conducted in shock tubes and a rapid compression machine (RCM) at nominal pressuresmore » of 20 and 40 atm, equivalence ratios of 0.5 and 1.0, and temperatures ranging from 650 to 1270 K. Results at temperatures above 900 K indicate that ignition delay time is similar for these fuels. However, RCM measurements below 900 K demonstrate a stronger negative temperature coefficient behavior for FACE F gasoline having lower octane sensitivity. In addition, RCM pressure profiles under two-stage ignition conditions illustrate that the magnitude of low-temperature heat release (LTHR) increases with decreasing fuel octane sensitivity. However, intermediate-temperature heat release is shown to increase as fuel octane sensitivity increases. Various surrogate fuel mixtures were formulated to conduct chemical kinetic modeling, and complex multicomponent surrogate mixtures were shown to reproduce experimentally observed trends better than simpler two- and three-component mixtures composed of n-heptane, iso-octane, and toluene. Measurements in a Cooperative Fuels Research (CFR) engine demonstrated that the multicomponent surrogates accurately captured the antiknock quality of the FACE gasolines. Simulations were performed using multicomponent surrogates for FACE F and G to reveal the underlying chemical kinetics linking fuel composition with ignition characteristics. Finally, a key discovery of this work is the kinetic coupling between aromatics and naphthenes, which affects the radical pool population and thereby controls ignition.« less

Phased Array 3D MR Spectroscopic Imaging of the Brain at 7 Tesla

PubMed Central

Xu, Duan; Cunningham, Charles H; Chen, Albert P.; Li, Yan; Kelley, Douglas AC; Mukherjee, Pratik; Pauly, John M.; Nelson, Sarah J.; Vigneron, Daniel B.

2008-01-01

Ultrahigh field 7T MR scanners offer the potential for greatly improved MR spectroscopic imaging due to increased sensitivity and spectral resolution. Prior 7T human single-voxel MRS studies have shown significant increases in SNR and spectral resolution as compared to lower magnetic fields, but have not demonstrated the increase in spatial resolution and multivoxel coverage possible with 7T MR spectroscopic imaging. The goal of this study was to develop specialized rf pulses and sequences for 3D MRSI at 7T to address the challenges of increased chemical shift misregistration, B1 power limitations, and increased spectral bandwidth. The new 7T MRSI sequence was tested in volunteer studies and demonstrated the feasibility of obtaining high SNR phased-array 3D MRSI from the human brain. PMID:18486386

Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A)-Mediated changes in Fas Expression and Fas-Dependent Apoptosis: Role of Lyn/Syk activation

PubMed Central

Incrocci, Ryan; Hussain, Samira; Stone, Amanda; Bieging, Kathryn; Alt, Lauren A.C.; Fay, Michael J.; Swanson-Mungerson, Michelle

2015-01-01

Epstein-Barr virus Latent Membrane Protein 2A (LMP2A) is expressed in EBV-infected B cells in the germinal center, a site of significant apoptosis induced by engagement of Fas on activated B cells. Signals from the B cell receptor (BCR) protect germinal center B cells from Fas-mediated apoptosis, and since LMP2A is a BCR mimic, we hypothesized that LMP2A would also protect B cells from Fas-mediated apoptosis. Surprisingly, latently-infected human and murine B cell lines expressing LMP2A were more sensitive to Fas-mediated apoptosis, as determined by increases in Annexin-V staining, and cleavage of caspase-8, −3 and PARP. Additional studies show that LMP2A-expressing B cell lines demonstrate a Lyn- and Syk-dependent increase in sensitivity to Fas-mediated apoptosis, due to an LMP2A-dependent enhancement in Fas expression. These findings demonstrate the ability for LMP2A to directly increase a pro-apoptotic molecule and have implications for EBV latency as well as the treatment of EBV-associated malignancies. PMID:26255694

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

PubMed Central

Merrill, Liana; Malley, Susan

2013-01-01

Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P ≤ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P ≤ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P ≤ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P ≤ 0.01) increased at all monofilament forces tested (0.1–4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P ≤ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity. PMID:23657640

Generation and Evaluation of Prophylactic mRNA Vaccines Against Allergy.

PubMed

Weiss, Richard; Scheiblhofer, Sandra; Thalhamer, Josef

2017-01-01

Due to the worldwide increase in allergies and a limited efficacy of therapeutic interventions, the need for prophylactic vaccination against allergies has been recognized. mRNA and DNA vaccines have demonstrated their high potential for preventing allergic sensitization by inducing an immunological bias that prevents TH2 sensitization. However, only mRNA vaccines fulfill the stringent safety requirements for vaccination of healthy children. In this chapter, we describe the generation of conventional as well as self-replicating mRNA vaccines and methods to test their prophylactic efficacy in animal models.

Voltage-induced ferromagnetic resonance in magnetic tunnel junctions.

PubMed

Zhu, Jian; Katine, J A; Rowlands, Graham E; Chen, Yu-Jin; Duan, Zheng; Alzate, Juan G; Upadhyaya, Pramey; Langer, Juergen; Amiri, Pedram Khalili; Wang, Kang L; Krivorotov, Ilya N

2012-05-11

We demonstrate excitation of ferromagnetic resonance in CoFeB/MgO/CoFeB magnetic tunnel junctions (MTJs) by the combined action of voltage-controlled magnetic anisotropy (VCMA) and spin transfer torque (ST). Our measurements reveal that GHz-frequency VCMA torque and ST in low-resistance MTJs have similar magnitudes, and thus that both torques are equally important for understanding high-frequency voltage-driven magnetization dynamics in MTJs. As an example, we show that VCMA can increase the sensitivity of an MTJ-based microwave signal detector to the sensitivity level of semiconductor Schottky diodes.

Development of a highly-sensitive Penning ionization electron spectrometer using the magnetic bottle effect

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

Ota, Masahiro; Ishiguro, Yuki; Nakajima, Yutaro

2016-02-01

This paper reports on a highly-sensitive retarding-type electron spectrometer for a continuous source of electrons, in which the electron collection efficiency is increased by utilizing the magnetic bottle effect. This study demonstrates an application to Penning ionization electron spectroscopy using collisional ionization with metastable He*(2{sup 3}S) atoms. Technical details and performances of the instrument are presented. This spectrometer can be used for studies of functional molecules and assemblies, and exterior electron densities are expected to be selectively observed by the Penning ionization.

USE OF EXPERT RATINGS AS SAMPLING STRATA FOR A MORE COST-EFFECTIVE PROBABILITY SAMPLE OF A RARE POPULATION

PubMed Central

McCaffrey, Daniel; Perlman, Judith; Marshall, Grant N.; Hambarsoomians, Katrin

2010-01-01

We consider situations in which externally observable characteristics allow experts to quickly categorize individual households as likely or unlikely to contain a member of a rare target population. This classification can form the basis of disproportionate stratified sampling such that households classified as “unlikely” are sampled at a lower rate than those classified as “likely,” thereby reducing screening costs. Design weights account for this approach and allow unbiased estimates for the target population. We demonstrate that with sensitivity and specificity of expert classification at least 70%, and ideally at least 80%, our approach can economically increase effective sample size for a rare population. We develop heuristics for implementing this approach and demonstrate that sensitivity drives design effects and screening costs whereas specificity only drives the latter. We demonstrate that the potential gains from this approach increase as the target population becomes rarer. We further show that for most applications, unlikely strata should be sampled at 1/6 to ½ the rate of likely strata. This approach was applied to a survey of Cambodian immigrants in which the 82% of households rated “unlikely” were sampled at ¼ the rate as “likely” households, reducing screening from 9.4 to 4.0 approaches per complete. Sensitivity and specificity were 86% and 91% respectively. Weighted estimation had a design effect of 1.26 so screening costs per effective sample size were reduced 47%. We also note that in this instance, expert classification appeared to be uncorrelated with survey outcomes of interest among eligibles. PMID:20936050

Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

PubMed Central

Lo, Yuan Hung; Peachey, Tom; Abramson, David; McCulloch, Andrew

2013-01-01

Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004) to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling. PMID:24222910

Flexible Graphene Transistor Architecture for Optical Sensor Technology

NASA Astrophysics Data System (ADS)

Ordonez, Richard Christopher

The unique electrical and optoelectronic properties of graphene allow tunable conductivity and broadband electromagnetic absorption that spans the ultraviolet and infrared regimes. However, in the current state-of-art graphene sensor architectures, junction resistance and doping concentration are predominant factors that affect signal strength and sensitivity. Unfortunately, graphene produces high contact resistances with standard electrode materials ( few kilo-ohms), therefore, signal is weak and large carrier concentrations are required to probe sensitivity. Moreover, the atomic thickness of graphene enables the potential for flexible electronics, but there has not been a successful graphene sensor architecture that demonstrates stable operation on flexible substrates and with minimal fabrication cost. In this study, the author explores a novel 3-terminal transistor architecture that integrates twodimensional graphene, liquid metal, and electrolytic gate dielectrics (LM-GFETs: Liquid Metal and Graphene Field-Effect Transistors ). The goal is to deliver a sensitive, flexible, and lightweight transistor architecture that will improve sensor technology and maneuverability. The reported high thermal conductivity of graphene provides potential for room-temperature thermal management without the need of thermal-electric and gas cooling systems that are standard in sensor platforms. Liquid metals provide a unique opportunity for conformal electrodes that maximize surface area contact, therefore, enable flexibility, lower contact resistance, and reduce damage to the graphene materials involved. Lastly, electrolytic gate dielectrics provide conformability and high capacitances needed for high on/off rations and electrostatic gating. Results demonstrated that with minimal fabrication steps the proposed flexible graphene transistor architecture demonstrated ambipolar current-voltage transfer characteristics that are comparable to the current state-of-the-art. An additional investigation demonstrated PN junction operation and the successful integration of the proposed architecture into an optoelectronic application with the use of semiconductor quantum dots in contact with the graphene material that acted as optical absorbers to increase detector gain. Applications that can benefit from such technology advancement include Nano-satellites (Nanosat), Underwater autonomous vehicles (UAV), and airborne platforms in which flexibility and sensitivity are critical parameters that must be optimized to increase mission duration and range.

"When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect.

PubMed

Salmon, Stefanie J; Adriaanse, Marieke A; De Vet, Emely; Fennis, Bob M; De Ridder, Denise T D

2014-01-01

Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion.

“When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

PubMed Central

Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

2014-01-01

Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion. PMID:25009523

Citizen science identifies the effects of nitrogen deposition, climate and tree species on epiphytic lichens across the UK.

PubMed

Welden, N A; Wolseley, P A; Ashmore, M R

2018-01-01

A national citizen survey quantified the abundance of epiphytic lichens that are known to be either sensitive or tolerant to nitrogen (N) deposition. Records were collected across the UK from over 10,000 individual trees of 22 deciduous species. Mean abundance of tolerant and sensitive lichens was related to mean N deposition rates and climatic variables at a 5 km scale, and the response of lichens was compared on the three most common trees (Quercus, Fraxinus and Acer) and by assigning all 22 tree species to three bark pH groups. The abundance of N-sensitive lichens on trunks decreased with increasing total N deposition, while that of N-tolerant lichens increased. The abundance of N-sensitive lichens on trunks was reduced close to a busy road, while the abundance of N-tolerant lichens increased. The abundance of N-tolerant lichen species on trunks was lower on Quercus and other low bark pH species, but the abundance of N-sensitive lichens was similar on different tree species. Lichen abundance relationships with total N deposition did not differ between tree species or bark pH groups. The response of N-sensitive lichens to reduced nitrogen was greater than to oxidised N, and the response of N-tolerant lichens was greater to oxidised N than to reduced N. There were differences in the response of N-sensitive and N-tolerant lichens to rainfall, humidity and temperature. Relationships with N deposition and climatic variables were similar for lichen presence on twigs as for lichen abundance on trunks, but N-sensitive lichens increased, rather than decreased, on twigs of Quercus/low bark pH species. The results demonstrate the unique power of citizen science to detect and quantify the air pollution impacts over a wide geographical range, and specifically to contribute to understanding of lichen responses to different chemical forms of N deposition, local pollution sources and bark chemistry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrophysiological Responses of Gustatory Receptor Neurons on the Labella of the Common Malaria Mosquito, Anopheles quadrimaculatus (Diptera: Culicidae).

PubMed

Sparks, Jackson T; Dickens, Joseph C

2016-05-11

We recorded electrical responses from sensory cells associated with gustatory sensilla on the labella of female Anopheles quadrimaculatus Say to salt, sucrose, quinine (a feeding deterrent), and the insect repellent, N,N-diethyl-3-methylbenzamide (DEET). A salt-sensitive cell responded to increasing concentrations of sodium chloride. A second cell was activated by increasing sucrose concentrations, while quinine, DEET, or a mixture of quinine + DEET elicited spike activity from a third cell, an apparent bitter- or deterrent-sensitive cell. Both quinine and DEET suppressed activity of the sugar-sensitive cell; sucrose suppressed activity of the bitter- or deterrent-sensitive cell. These results demonstrate separate gustatory pathways for a feeding stimulant and aversive contact cues mediated through distinct sensory inputs on the labellum. This sensory appendage may serve as a useful target to disrupt feeding behavior in this and other anopheline species, which transmit diseases like malaria to human populations. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the United States.

Study of the influence of the agarose hydrogel layer thickness on sensitivity of the coated silica microsphere resonator to humidity.

PubMed

Mallik, Arun Kumar; Farrell, Gerald; Wu, Qiang; Semenova, Yuliya

2017-05-10

In this paper, we investigate both theoretically and experimentally the influence of the agarose hydrogel layer thickness on the sensitivity of a proposed relative humidity (RH) sensor based on a silica microsphere resonator coated with agarose hydrogel. The operating principle of the sensor relies on excitation of whispering gallery modes (WGMs) in the coated silica microsphere using the evanescent field of a tapered fiber. A change in the ambient relative humidity is detected by measuring the wavelength shift of the WGMs in the transmission spectrum of the tapered fiber. Using perturbation theory, we analyze the influence of the agarose coating thickness on the sensitivity of the proposed sensor and compare the results of this analysis with experimental findings for different coating layer thicknesses. We demonstrate that an increase in the coating layer thickness initially leads to an increase in the sensitivity to RH and reaches saturation at higher values of the agarose layer thickness. The results of the study are useful for the design and optimization of microsphere sensor parameters to meet a performance specification.

Evaluation of joint effusion in rabbits by color Doppler, power Doppler, and contrast-enhanced power Doppler ultrasonography.

PubMed

Lim, Gye-Yeon; Im, Soo Ah; Jung, Won Sang; Lee, Jae Mun; Lee, Ah Won

2005-09-01

The aim of this prospective study was to evaluate the diagnostic value of power Doppler ultrasonography (PDUS) and contrast-enhanced PDUS (CEPDUS) in the depiction and characterization of experimentally induced arthritis in the rabbit. Thirty rabbits were divided into three groups consisting of one control group (saline injection group) and two experimental groups: a suppurative arthritis group and a chemically induced synovitis group. The same amount (1 ml) of each agent was directly injected into the right hip joint. Serial color Doppler ultrasound (CDUS), PDUS, and CEPDUS images were obtained before and after injection. We observed that all of the infected knees in the suppurative arthritis group with Staphylococcus aureus demonstrated an increased signal on PDUS after inoculation. A minimal power Doppler signal was presented in the chemically induced synovitis group with talc injection, but none of the control knees demonstrated any increased signals. CEPDUS was the most sensitive imaging modality for evaluating the increase of blood flows in suppurative arthritis and was subsequently followed by PDUS and CDUS. The increased signals obtained with PDUS represent increased local blood flows; therefore, this technique can be used for evaluating the degree of inflammation. Furthermore, using the contrast agent enhances the sensitivity of PDUS, and it can even be useful for differentiating borderline cases. Copyright 2005 Wiley Periodicals, Inc

Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid.

PubMed

Drewes, Asbjørn-Mohr; Reddy, Hariprasad; Staahl, Camilla; Pedersen, Jan; Funch-Jensen, Peter; Arendt-Nielsen, Lars; Gregersen, Hans

2005-07-28

Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization. Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine. The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change. Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs.

Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid

PubMed Central

Drewes, Asbjorn Mohr; Reddy, Hariprasad; Staahl, Camilla; Pedersen, Jan; Funch-Jensen, Peter; Arendt-Nielsen, Lars; Gregersen, Hans

2005-01-01

AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization. METHODS: Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine. RESULTS: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change. CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs. PMID:16038036

Comparison of standard- and nano-flow liquid chromatography platforms for MRM-based quantitation of putative plasma biomarker proteins.

PubMed

Percy, Andrew J; Chambers, Andrew G; Yang, Juncong; Domanski, Dominik; Borchers, Christoph H

2012-09-01

The analytical performance of a standard-flow ultra-high-performance liquid chromatography (UHPLC) and a nano-flow high-performance liquid chromatography (HPLC) system, interfaced to the same state-of-the-art triple-quadrupole mass spectrometer, were compared for the multiple reaction monitoring (MRM)-mass spectrometry (MS)-based quantitation of a panel of 48 high-to-moderate-abundance cardiovascular disease-related plasma proteins. After optimization of the MRM transitions for sensitivity and testing for chemical interference, the optimum sensitivity, loading capacity, gradient, and retention-time reproducibilities were determined. We previously demonstrated the increased robustness of the standard-flow platform, but we expected that the standard-flow platform would have an overall lower sensitivity. This study was designed to determine if this decreased sensitivity could be compensated for by increased sample loading. Significantly fewer interferences with the MRM transitions were found for the standard-flow platform than for the nano-flow platform (2 out of 103 transitions compared with 42 out of 103 transitions, respectively), which demonstrates the importance of interference-testing when nano-flow systems are used. Using only interference-free transitions, 36 replicate LC/MRM-MS analyses resulted in equal signal reproducibilities between the two platforms (9.3 % coefficient of variation (CV) for 88 peptide targets), with superior retention-time precision for the standard-flow platform (0.13 vs. 6.1 % CV). Surprisingly, for 41 of the 81 proteotypic peptides in the final assay, the standard-flow platform was more sensitive while for 9 of 81 the nano-flow platform was more sensitive. For these 81 peptides, there was a good correlation between the two sets of results (R(2) = 0.98, slope = 0.97). Overall, the standard-flow platform had superior performance metrics for most peptides, and is a good choice if sufficient sample is available.

Systematic review of randomised controlled trials of the effects of caffeine or caffeinated drinks on blood glucose concentrations and insulin sensitivity in people with diabetes mellitus.

PubMed

Whitehead, N; White, H

2013-04-01

Compounds other than macronutrients have been shown to influence blood glucose concentrations and insulin sensitivity in people with diabetes, with caffeine being one such substance. The present study systematically reviewed the evidence of the effects of caffeine on blood glucose concentrations and/or insulin sensitivity in people with diabetes. Four databases, including MEDLINE and EMBASE, were searched up to 1 February 2012. Randomised controlled trials (RCTs) investigating the effects of caffeine on blood glucose and/or insulin sensitivity in humans, diagnosed with type I, type II or gestational diabetes mellitus (GDM), were included. Quality assessment and data extraction were conducted and agreed by both authors. Of 253 articles retrieved, nine trials (134 participants) were identified. Trials in people with type II diabetes demonstrated that the ingestion of caffeine (approximately 200-500 mg) significantly increased blood glucose concentrations by 16-28% of the area under the curve (AUC) and insulin concentrations by 19-48% of the AUC when taken prior to a glucose load, at the same time as decreasing insulin sensitivity by 14-37%. In type I diabetes, trials indicated enhanced recognition and a reduced duration of hypoglycaemic episodes following ingestion of 400-500 mg caffeine, without altering glycated haemoglobin. In GDM, a single trial demonstrated that approximately 200 mg of caffeine induced a decrease in insulin sensitivity by 18% and a subsequent increase in blood glucose concentrations by 19% of the AUC. Evidence indicates a negative effect of caffeine intake on blood glucose control in individuals with type II diabetes, as replicated in a single trial in GDM. Larger-scale RCTs of longer duration are needed to determine the effects of timing and dose. Early indications of a reduced duration and an improved awareness of hypoglycaemia in type I diabetes require further confirmation. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

Modeling the Sensitivity of Field Surveys for Detection of Environmental DNA (eDNA)

PubMed Central

Schultz, Martin T.; Lance, Richard F.

2015-01-01

The environmental DNA (eDNA) method is the practice of collecting environmental samples and analyzing them for the presence of a genetic marker specific to a target species. Little is known about the sensitivity of the eDNA method. Sensitivity is the probability that the target marker will be detected if it is present in the water body. Methods and tools are needed to assess the sensitivity of sampling protocols, design eDNA surveys, and interpret survey results. In this study, the sensitivity of the eDNA method is modeled as a function of ambient target marker concentration. The model accounts for five steps of sample collection and analysis, including: 1) collection of a filtered water sample from the source; 2) extraction of DNA from the filter and isolation in a purified elution; 3) removal of aliquots from the elution for use in the polymerase chain reaction (PCR) assay; 4) PCR; and 5) genetic sequencing. The model is applicable to any target species. For demonstration purposes, the model is parameterized for bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix) assuming sampling protocols used in the Chicago Area Waterway System (CAWS). Simulation results show that eDNA surveys have a high false negative rate at low concentrations of the genetic marker. This is attributed to processing of water samples and division of the extraction elution in preparation for the PCR assay. Increases in field survey sensitivity can be achieved by increasing sample volume, sample number, and PCR replicates. Increasing sample volume yields the greatest increase in sensitivity. It is recommended that investigators estimate and communicate the sensitivity of eDNA surveys to help facilitate interpretation of eDNA survey results. In the absence of such information, it is difficult to evaluate the results of surveys in which no water samples test positive for the target marker. It is also recommended that invasive species managers articulate concentration-based sensitivity objectives for eDNA surveys. In the absence of such information, it is difficult to design appropriate sampling protocols. The model provides insights into how sampling protocols can be designed or modified to achieve these sensitivity objectives. PMID:26509674

Modeling the Sensitivity of Field Surveys for Detection of Environmental DNA (eDNA).

PubMed

Schultz, Martin T; Lance, Richard F

2015-01-01

The environmental DNA (eDNA) method is the practice of collecting environmental samples and analyzing them for the presence of a genetic marker specific to a target species. Little is known about the sensitivity of the eDNA method. Sensitivity is the probability that the target marker will be detected if it is present in the water body. Methods and tools are needed to assess the sensitivity of sampling protocols, design eDNA surveys, and interpret survey results. In this study, the sensitivity of the eDNA method is modeled as a function of ambient target marker concentration. The model accounts for five steps of sample collection and analysis, including: 1) collection of a filtered water sample from the source; 2) extraction of DNA from the filter and isolation in a purified elution; 3) removal of aliquots from the elution for use in the polymerase chain reaction (PCR) assay; 4) PCR; and 5) genetic sequencing. The model is applicable to any target species. For demonstration purposes, the model is parameterized for bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix) assuming sampling protocols used in the Chicago Area Waterway System (CAWS). Simulation results show that eDNA surveys have a high false negative rate at low concentrations of the genetic marker. This is attributed to processing of water samples and division of the extraction elution in preparation for the PCR assay. Increases in field survey sensitivity can be achieved by increasing sample volume, sample number, and PCR replicates. Increasing sample volume yields the greatest increase in sensitivity. It is recommended that investigators estimate and communicate the sensitivity of eDNA surveys to help facilitate interpretation of eDNA survey results. In the absence of such information, it is difficult to evaluate the results of surveys in which no water samples test positive for the target marker. It is also recommended that invasive species managers articulate concentration-based sensitivity objectives for eDNA surveys. In the absence of such information, it is difficult to design appropriate sampling protocols. The model provides insights into how sampling protocols can be designed or modified to achieve these sensitivity objectives.

Stress-dependent elastic properties of shales—laboratory experiments at seismic and ultrasonic frequencies

NASA Astrophysics Data System (ADS)

Szewczyk, Dawid; Bauer, Andreas; Holt, Rune M.

2018-01-01

Knowledge about the stress sensitivity of elastic properties and velocities of shales is important for the interpretation of seismic time-lapse data taken as part of reservoir and caprock surveillance of both unconventional and conventional oil and gas fields (e.g. during 4-D monitoring of CO2 storage). Rock physics models are often developed based on laboratory measurements at ultrasonic frequencies. However, as shown previously, shales exhibit large seismic dispersion, and it is possible that stress sensitivities of velocities are also frequency dependent. In this work, we report on a series of seismic and ultrasonic laboratory tests in which the stress sensitivity of elastic properties of Mancos shale and Pierre shale I were investigated. The shales were tested at different water saturations. Dynamic rock engineering parameters and elastic wave velocities were examined on core plugs exposed to isotropic loading. Experiments were carried out in an apparatus allowing for static-compaction and dynamic measurements at seismic and ultrasonic frequencies within single test. For both shale types, we present and discuss experimental results that demonstrate dispersion and stress sensitivity of the rock stiffness, as well as P- and S-wave velocities, and stiffness anisotropy. Our experimental results show that the stress-sensitivity of shales is different at seismic and ultrasonic frequencies, which can be linked with simultaneously occurring changes in the dispersion with applied stress. Measured stress sensitivity of elastic properties for relatively dry samples was higher at seismic frequencies however, the increasing saturation of shales decreases the difference between seismic and ultrasonic stress-sensitivities, and for moist samples stress-sensitivity is higher at ultrasonic frequencies. Simultaneously, the increased saturation highly increases the dispersion in shales. We have also found that the stress-sensitivity is highly anisotropic in both shales and that in some of the cases higher stress-sensitivity of elastic properties can be seen in the direction parallel to the bedding plane.

A neural hypothesis for stress-induced headache.

PubMed

Cathcart, Stuart

2009-12-01

The mechanisms by which stress contributes to CTH are not clearly understood. The commonly accepted notion of muscle hyper-reactivity to stress in CTH sufferers is not supported in the research data. We propose a neural model whereby stress acts supra-spinally to aggravate already increased pain sensitivity in CTH sufferers. Indirect support for the model comes from emerging research elucidating complex supra-spinal networks through which psychological stress may contribute to and even cause pain. Similarly, emerging research demonstrates supra-spinal pain processing abnormalities in CTH sufferers. While research with CTH sufferers offering direct support for the model is lacking at present, initial work by our group is consistent with the models predictions, particularly, that stress aggravates already increased pain sensitivity in CTH sufferers.

A sub-sampled approach to extremely low-dose STEM

DOE PAGES

Stevens, A.; Luzi, L.; Yang, H.; ...

2018-01-22

The inpainting of deliberately and randomly sub-sampled images offers a potential means to image specimens at a high resolution and under extremely low-dose conditions (≤1 e -/Å 2) using a scanning transmission electron microscope. We show that deliberate sub-sampling acquires images at least an order of magnitude faster than conventional low-dose methods for an equivalent electron dose. More importantly, when adaptive sub-sampling is implemented to acquire the images, there is a significant increase in the resolution and sensitivity which accompanies the increase in imaging speed. Lastly, we demonstrate the potential of this method for beam sensitive materials and in-situ observationsmore » by experimentally imaging the node distribution in a metal-organic framework.« less

Compressing turbulence and sudden viscous dissipation with compression-dependent ionization state

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

Davidovits, Seth; Fisch, Nathaniel J.

Turbulent plasma flow, amplified by rapid three-dimensional compression, can be suddenly dissipated under continuing compression. Furthermore, this effect relies on the sensitivity of the plasma viscosity to the temperature, μ ~ T 5 / 2 . The plasma viscosity is also sensitive to the plasma ionization state. Here, we show that the sudden dissipation phenomenon may be prevented when the plasma ionization state increases during compression, and we demonstrate the regime of net viscosity dependence on compression where sudden dissipation is guaranteed. In addition, it is shown that, compared to cases with no ionization, ionization during compression is associated withmore » larger increases in turbulent energy and can make the difference between growing and decreasing turbulent energy.« less

Compressing turbulence and sudden viscous dissipation with compression-dependent ionization state

DOE PAGES

Davidovits, Seth; Fisch, Nathaniel J.

2016-11-14

Turbulent plasma flow, amplified by rapid three-dimensional compression, can be suddenly dissipated under continuing compression. Furthermore, this effect relies on the sensitivity of the plasma viscosity to the temperature, μ ~ T 5 / 2 . The plasma viscosity is also sensitive to the plasma ionization state. Here, we show that the sudden dissipation phenomenon may be prevented when the plasma ionization state increases during compression, and we demonstrate the regime of net viscosity dependence on compression where sudden dissipation is guaranteed. In addition, it is shown that, compared to cases with no ionization, ionization during compression is associated withmore » larger increases in turbulent energy and can make the difference between growing and decreasing turbulent energy.« less

A sub-sampled approach to extremely low-dose STEM

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

Stevens, A.; Luzi, L.; Yang, H.

The inpainting of deliberately and randomly sub-sampled images offers a potential means to image specimens at a high resolution and under extremely low-dose conditions (≤1 e -/Å 2) using a scanning transmission electron microscope. We show that deliberate sub-sampling acquires images at least an order of magnitude faster than conventional low-dose methods for an equivalent electron dose. More importantly, when adaptive sub-sampling is implemented to acquire the images, there is a significant increase in the resolution and sensitivity which accompanies the increase in imaging speed. Lastly, we demonstrate the potential of this method for beam sensitive materials and in-situ observationsmore » by experimentally imaging the node distribution in a metal-organic framework.« less

Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the locomotor stimulating effects of cocaine in adolescent female rats.

PubMed

Serafine, Katherine M; Labay, Caitlin; France, Charles P

2016-08-01

Eating a diet high in fat can lead to obesity, chronic metabolic disease, and increased inflammation in both the central and peripheral nervous systems. Dietary supplements that are high in omega-3 polyunsaturated fatty acids can reduce or prevent these negative health consequences in rats. Eating high fat chow also increases the sensitivity of rats to behavioral effects of drugs acting on dopamine systems (e.g., cocaine), and this effect is greatest in adolescent females. The present experiment tested the hypothesis that dietary supplementation with fish oil prevents high fat chow induced increases in sensitivity to cocaine in adolescent female rats. Female Sprague-Dawley rats (post-natal day 25-27) ate standard laboratory chow (5.7% fat), high fat chow (34.4% fat), or high fat chow supplemented with fish oil (20% w/w). Cocaine dose dependently (1-17.8mg/kg) increased locomotion and induced sensitization across 6 weeks of once-weekly testing in all rats; however, these effects were greatest in rats eating high fat chow. Dietary supplementation with fish oil prevented enhanced locomotion and sensitization in rats eating high fat chow. There were no differences in inflammatory markers in plasma or the hypothalamus among dietary conditions. These results demonstrate that dietary supplementation with fish oil can prevent high fat diet-induced sensitization to cocaine, but they fail to support the view that these effects are due to changes in proinflammatory cytokines. These data add to a growing literature on the relationship between diet and drug abuse and extend the potential health benefits of fish oil to stimulant drug abuse prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the locomotor stimulating effects of cocaine in adolescent female rats

PubMed Central

Serafine, Katherine M.; Labay, Caitlin; France, Charles P.

2016-01-01

BACKGROUND Eating a diet high in fat can lead to obesity, chronic metabolic disease, and increased inflammation in both the central and peripheral nervous systems. Dietary supplements that are high in omega-3 polyunsaturated fatty acids can reduce or prevent these negative health consequences in rats. Eating high fat chow also increases the sensitivity of rats to behavioral effects of drugs acting on dopamine systems (e.g., cocaine), and this effect is greatest in adolescent females. METHODS The present experiment tested the hypothesis that dietary supplementation with fish oil prevents high fat chow induced increases in sensitivity to cocaine in adolescent female rats. Female Sprague-Dawley rats (post-natal day 25–27) ate standard laboratory chow (5.7% fat), high fat chow (34.4% fat), or high fat chow supplemented with fish oil (20% w/w). Cocaine dose dependently (1–17.8 mg/kg) increased locomotion and induced sensitization across 6 weeks of once-weekly testing in all rats; however, these effects were greatest in rats eating high fat chow. RESULTS Dietary supplementation with fish oil prevented enhanced locomotion and sensitization in rats eating high fat chow. There were no differences in inflammatory markers in plasma or the hypothalamus among dietary conditions. CONCLUSIONS These results demonstrate that dietary supplementation with fish oil can prevent high fat diet-induced sensitization to cocaine, but they fail to support the view that these effects are due to changes in proinflammatory cytokines. These data add to a growing literature on the relationship between diet and drug abuse and extend the potential health benefits of fish oil to stimulant drug abuse prevention. PMID:27242289

Sensitivity of wildlife habitat models to uncertainties in GIS data

NASA Technical Reports Server (NTRS)

Stoms, David M.; Davis, Frank W.; Cogan, Christopher B.

1992-01-01

Decision makers need to know the reliability of output products from GIS analysis. For many GIS applications, it is not possible to compare these products to an independent measure of 'truth'. Sensitivity analysis offers an alternative means of estimating reliability. In this paper, we present a CIS-based statistical procedure for estimating the sensitivity of wildlife habitat models to uncertainties in input data and model assumptions. The approach is demonstrated in an analysis of habitat associations derived from a GIS database for the endangered California condor. Alternative data sets were generated to compare results over a reasonable range of assumptions about several sources of uncertainty. Sensitivity analysis indicated that condor habitat associations are relatively robust, and the results have increased our confidence in our initial findings. Uncertainties and methods described in the paper have general relevance for many GIS applications.

Spatial and spectral characterization of acid rain stress in Canadian Shield lakes

NASA Technical Reports Server (NTRS)

Marshall, Elizabeth J.; Tanis, Frederick J.

1989-01-01

Results from this study demonstrate that a remote sensor can discriminate lake clarity based upon reflection. The basic hypothesis was that seasonal and multiyear changes in lake optical transparency are indicative of sensitivity to acidic deposition. In many acid-sensitive lakes optical transparency is controlled by the amount of dissolved organic carbon (DOC) present. DOC is a strong absorbing, nonscattering material which has the greatest impact at short visible wavelengths, including Thematic Mapper band 1. Acid-sensitive lakes have high concentrations of aluminum which have been mobilized by acidic components contained in the runoff. Aluminum complexing with DOC is considered to be the primary mechanism to account for observed increases in lake transparency in acid-sensitive lakes. Thus seasonal changes in the optical transparency of lakes should provide an indication of the stress due to acid deposition and loading.

Influence of increased mechanical loading by hypergravity on the microtubule cytoskeleton and prostaglandin E2 release in primary osteoblasts

NASA Technical Reports Server (NTRS)

Searby, Nancy D.; Steele, Charles R.; Globus, Ruth K.

2005-01-01

Cells respond to a wide range of mechanical stimuli such as fluid shear and strain, although the contribution of gravity to cell structure and function is not understood. We hypothesized that bone-forming osteoblasts are sensitive to increased mechanical loading by hypergravity. A centrifuge suitable for cell culture was developed and validated, and then primary cultures of fetal rat calvarial osteoblasts at various stages of differentiation were mechanically loaded using hypergravity. We measured microtubule network morphology as well as release of the paracrine factor prostaglandin E2 (PGE2). In immature osteoblasts, a stimulus of 10x gravity (10 g) for 3 h increased PGE2 2.5-fold and decreased microtubule network height 1.12-fold without affecting cell viability. Hypergravity (3 h) caused dose-dependent (5-50 g) increases in PGE2 (5.3-fold at 50 g) and decreases (1.26-fold at 50 g) in microtubule network height. PGE2 release depended on duration but not orientation of the hypergravity load. As osteoblasts differentiated, sensitivity to hypergravity declined. We conclude that primary osteoblasts demonstrate dose- and duration-dependent sensitivity to gravitational loading, which appears to be blunted in mature osteoblasts.

Expressing negative emotions to children: Mothers' aversion sensitivity and children's adjustment.

PubMed

Moed, Anat; Dix, Theodore; Anderson, Edward R; Greene, Shannon M

2017-03-01

Research is unclear about when expressing negative emotions to children performs valuable socialization and regulatory functions and when, instead, it undermines children's adjustment. In this study, we isolated 1 kind of negative expression to test the aversion sensitivity hypothesis: that rapid increases in mothers' negativity as a function of increases in the aversiveness of children's behavior are uniquely problematic for children. During multiple assessments of a divorcing sample over 2 years (N = 284), 12-min interactions between mothers and their 4- to 11-year-old children were recorded. Forty-seven observed child behaviors were ranked from low to high aversive. Within-dyad changes demonstrated that mothers' general negativity-their tendency to express negative emotion at high rates-was unrelated to children's adjustment. In contrast, mothers' aversion-focused negativity-their tendency to increase negative emotional expression rapidly as the aversiveness of children's behavior increased-predicted children's poor social competence, poor emotion regulation, and externalizing behavior problems at the next assessment. The findings suggest that negative expression that reflects mothers' affective sensitivity to aversive child behavior may promote interaction patterns and adaptations in children that are particularly likely to place children at risk for adjustment problems. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Organic-on-silicon complementary metal-oxide-semiconductor colour image sensors.

PubMed

Lim, Seon-Jeong; Leem, Dong-Seok; Park, Kyung-Bae; Kim, Kyu-Sik; Sul, Sangchul; Na, Kyoungwon; Lee, Gae Hwang; Heo, Chul-Joon; Lee, Kwang-Hee; Bulliard, Xavier; Satoh, Ryu-Ichi; Yagi, Tadao; Ro, Takkyun; Im, Dongmo; Jung, Jungkyu; Lee, Myungwon; Lee, Tae-Yon; Han, Moon Gyu; Jin, Yong Wan; Lee, Sangyoon

2015-01-12

Complementary metal-oxide-semiconductor (CMOS) colour image sensors are representative examples of light-detection devices. To achieve extremely high resolutions, the pixel sizes of the CMOS image sensors must be reduced to less than a micron, which in turn significantly limits the number of photons that can be captured by each pixel using silicon (Si)-based technology (i.e., this reduction in pixel size results in a loss of sensitivity). Here, we demonstrate a novel and efficient method of increasing the sensitivity and resolution of the CMOS image sensors by superposing an organic photodiode (OPD) onto a CMOS circuit with Si photodiodes, which consequently doubles the light-input surface area of each pixel. To realise this concept, we developed organic semiconductor materials with absorption properties selective to green light and successfully fabricated highly efficient green-light-sensitive OPDs without colour filters. We found that such a top light-receiving OPD, which is selective to specific green wavelengths, demonstrates great potential when combined with a newly designed Si-based CMOS circuit containing only blue and red colour filters. To demonstrate the effectiveness of this state-of-the-art hybrid colour image sensor, we acquired a real full-colour image using a camera that contained the organic-on-Si hybrid CMOS colour image sensor.

Organic-on-silicon complementary metal–oxide–semiconductor colour image sensors

PubMed Central

Lim, Seon-Jeong; Leem, Dong-Seok; Park, Kyung-Bae; Kim, Kyu-Sik; Sul, Sangchul; Na, Kyoungwon; Lee, Gae Hwang; Heo, Chul-Joon; Lee, Kwang-Hee; Bulliard, Xavier; Satoh, Ryu-Ichi; Yagi, Tadao; Ro, Takkyun; Im, Dongmo; Jung, Jungkyu; Lee, Myungwon; Lee, Tae-Yon; Han, Moon Gyu; Jin, Yong Wan; Lee, Sangyoon

2015-01-01

Complementary metal–oxide–semiconductor (CMOS) colour image sensors are representative examples of light-detection devices. To achieve extremely high resolutions, the pixel sizes of the CMOS image sensors must be reduced to less than a micron, which in turn significantly limits the number of photons that can be captured by each pixel using silicon (Si)-based technology (i.e., this reduction in pixel size results in a loss of sensitivity). Here, we demonstrate a novel and efficient method of increasing the sensitivity and resolution of the CMOS image sensors by superposing an organic photodiode (OPD) onto a CMOS circuit with Si photodiodes, which consequently doubles the light-input surface area of each pixel. To realise this concept, we developed organic semiconductor materials with absorption properties selective to green light and successfully fabricated highly efficient green-light-sensitive OPDs without colour filters. We found that such a top light-receiving OPD, which is selective to specific green wavelengths, demonstrates great potential when combined with a newly designed Si-based CMOS circuit containing only blue and red colour filters. To demonstrate the effectiveness of this state-of-the-art hybrid colour image sensor, we acquired a real full-colour image using a camera that contained the organic-on-Si hybrid CMOS colour image sensor. PMID:25578322

Enhancement of photoluminescence intensity of erbium doped silica containing Ge nanocrystals: distance dependent interactions

NASA Astrophysics Data System (ADS)

Manna, S.; Aluguri, R.; Bar, R.; Das, S.; Prtljaga, N.; Pavesi, L.; Ray, S. K.

2015-01-01

Photo-physical processes in Er-doped silica glass matrix containing Ge nanocrystals prepared by the sol-gel method are presented in this article. Strong photoluminescence at 1.54 μm, important for fiber optics telecommunication systems, is observed from the different sol-gel derived glasses at room temperature. We demonstrate that Ge nanocrystals act as strong sensitizers for Er3+ ions emission and the effective Er excitation cross section increases by almost four orders of magnitude with respect to the one without Ge nanocrystals. Rate equations are considered to demonstrate the sensitization of erbium luminescence by Ge nanocrystals. Analyzing the erbium effective excitation cross section, extracted from the flux dependent rise and decay times, a Dexter type of short range energy transfer from a Ge nanocrystal to erbium ion is established.

Relationship of Triamine-Biocide Tolerance of Salmonella enterica Serovar Senftenberg to Antimicrobial Susceptibility, Serum Resistance and Outer Membrane Proteins.

PubMed

Futoma-Kołoch, Bożena; Dudek, Bartłomiej; Kapczyńska, Katarzyna; Krzyżewska, Eva; Wańczyk, Martyna; Korzekwa, Kamila; Rybka, Jacek; Klausa, Elżbieta; Bugla-Płoskońska, Gabriela

2017-07-11

A new emerging phenomenon is the association between the incorrect use of biocides in the process of disinfection in farms and the emergence of cross-resistance in Salmonella populations. Adaptation of the microorganisms to the sub-inhibitory concentrations of the disinfectants is not clear, but may result in an increase of sensitivity or resistance to antibiotics, depending on the biocide used and the challenged Salmonella serovar. Exposure of five Salmonella enterica subsp. enterica serovar Senftenberg ( S. Senftenberg) strains to triamine-containing disinfectant did not result in variants with resistance to antibiotics, but has changed their susceptibility to normal human serum (NHS). Three biocide variants developed reduced sensitivity to NHS in comparison to the sensitive parental strains, while two isolates lost their resistance to serum. For S. Senftenberg, which exhibited the highest triamine tolerance (6 × MIC) and intrinsic sensitivity to 22.5% and 45% NHS, a downregulation of flagellin and enolase has been demonstrated, which might suggest a lower adhesion and virulence of the bacteria. This is the first report demonstrating the influence of biocide tolerance on NHS resistance. In conclusion, there was a potential in S. Senftenberg to adjust to the conditions, where the biocide containing triamine was present. However, the adaptation did not result in the increase of antibiotic resistance, but manifested in changes within outer membrane proteins' patterns. The strategy of bacterial membrane proteins' analysis provides an opportunity to adjust the ways of infection treatments, especially when it is connected to the life-threating bacteremia caused by Salmonella species.

Relationship of Triamine-Biocide Tolerance of Salmonella enterica Serovar Senftenberg to Antimicrobial Susceptibility, Serum Resistance and Outer Membrane Proteins

PubMed Central

Futoma-Kołoch, Bożena; Dudek, Bartłomiej; Kapczyńska, Katarzyna; Wańczyk, Martyna; Korzekwa, Kamila; Rybka, Jacek; Klausa, Elżbieta; Bugla-Płoskońska, Gabriela

2017-01-01

A new emerging phenomenon is the association between the incorrect use of biocides in the process of disinfection in farms and the emergence of cross-resistance in Salmonella populations. Adaptation of the microorganisms to the sub-inhibitory concentrations of the disinfectants is not clear, but may result in an increase of sensitivity or resistance to antibiotics, depending on the biocide used and the challenged Salmonella serovar. Exposure of five Salmonella enterica subsp. enterica serovar Senftenberg (S. Senftenberg) strains to triamine-containing disinfectant did not result in variants with resistance to antibiotics, but has changed their susceptibility to normal human serum (NHS). Three biocide variants developed reduced sensitivity to NHS in comparison to the sensitive parental strains, while two isolates lost their resistance to serum. For S. Senftenberg, which exhibited the highest triamine tolerance (6 × MIC) and intrinsic sensitivity to 22.5% and 45% NHS, a downregulation of flagellin and enolase has been demonstrated, which might suggest a lower adhesion and virulence of the bacteria. This is the first report demonstrating the influence of biocide tolerance on NHS resistance. In conclusion, there was a potential in S. Senftenberg to adjust to the conditions, where the biocide containing triamine was present. However, the adaptation did not result in the increase of antibiotic resistance, but manifested in changes within outer membrane proteins’ patterns. The strategy of bacterial membrane proteins’ analysis provides an opportunity to adjust the ways of infection treatments, especially when it is connected to the life-threating bacteremia caused by Salmonella species. PMID:28696348

Enhancing sensitivity of high resolution optical coherence tomography using an optional spectrally encoded extended source (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yu, Xiaojun; Liu, Xinyu; Chen, Si; Wang, Xianghong; Liu, Linbo

2016-03-01

High-resolution optical coherence tomography (OCT) is of critical importance to disease diagnosis because it is capable of providing detailed microstructural information of the biological tissues. However, a compromise usually has to be made between its spatial resolutions and sensitivity due to the suboptimal spectral response of the system components, such as the linear camera, the dispersion grating, and the focusing lenses, etc. In this study, we demonstrate an OCT system that achieves both high spatial resolutions and enhanced sensitivity through utilizing a spectrally encoded source. The system achieves a lateral resolution of 3.1 μm and an axial resolution of 2.3 μm in air; when with a simple dispersive prism placed in the infinity space of the sample arm optics, the illumination beam on the sample is transformed into a line source with a visual angle of 10.3 mrad. Such an extended source technique allows a ~4 times larger maximum permissible exposure (MPE) than its point source counterpart, which thus improves the system sensitivity by ~6dB. In addition, the dispersive prism can be conveniently switched to a reflector. Such flexibility helps increase the penetration depth of the system without increasing the complexity of the current point source devices. We conducted experiments to characterize the system's imaging capability using the human fingertip in vivo and the swine eye optic never disc ex vivo. The higher penetration depth of such a system over the conventional point source OCT system is also demonstrated in these two tissues.

Cytochrome c conformations resolved by the photon counting histogram: Watching the alkaline transition with single-molecule sensitivity

PubMed Central

Perroud, Thomas D.; Bokoch, Michael P.; Zare, Richard N.

2005-01-01

We apply the photon counting histogram (PCH) model, a fluorescence technique with single-molecule sensitivity, to study pH-induced conformational changes of cytochrome c. PCH is able to distinguish different protein conformations based on the brightness of a fluorophore sensitive to its local environment. We label cytochrome c through its single free cysteine with tetramethylrhodamine-5-maleimide (TMR), a fluorophore with specific brightnesses that we associate with specific protein conformations. Ensemble measurements demonstrate two different fluorescence responses with increasing pH: (i) a decrease in fluorescence intensity caused by the alkaline transition of cytochrome c (pH 7.0–9.5), and (ii) an increase in intensity when the protein unfolds (pH 9.5–10.8). The magnitudes of these two responses depend strongly on the molar ratio of TMR used to label cytochrome c. Using PCH we determine that this effect arises from the proportion of a nonfunctional conformation in the sample, which can be differentiated from the functional conformation. We further determine the causes of each ensemble fluorescence response: (i) during the alkaline transition, the fluorophore enters a dark state and discrete conformations are observed, and (ii) as cytochrome c unfolds, the fluorophore incrementally brightens, but discrete conformations are no longer resolved. Moreover, we also show that functional TMR-cytochrome c undergoes a response of identical magnitude regardless of the proportion of nonfunctional protein in the sample. As expected for a technique with single-molecule sensitivity, we demonstrate that PCH can directly observe the most relevant conformation, unlike ensemble fluorometry. PMID:16314563

Au/NiFe/M(Au, MoS2, graphene) trilayer magnetoplasmonics DNA-hybridized sensors with high record of sensitivity

NASA Astrophysics Data System (ADS)

Faridi, Ehsan; Moradi, Maryam; Ansari, Narges; Ghasemi, Amir Hossein Baradaran; Afshar, Amir; Mohseni, Seyed Majid

2017-12-01

The demonstration of biosensors based on the surface plasmon effect holds promise for future high-sensitive electrodeless biodetection. The combination of magnetic effects with surface plasmon waves brings additional freedom to improve sensitivity and signal selectivity. Stacking biosensors with two-dimensional (2-D) materials, e.g., graphene (Gr) and MoS2, can influence plasmon waves and facilitate surface physiochemical properties as additional versatility aspects. We demonstrate magnetoplasmonic biosensors through the detuning of surface plasmon oscillation modes affected by magnetic effect via the presence of the NiFe (Py) layer and different light absorbers of Gr, MoS2, and Au ultrathin layers in three stacks of Au/Py/M(MoS2, Gr, Au) trilayers. We found minimum reflection, resonance angle shift, and transverse magneto-optical Kerr effect (TMOKE) responses of all sensors in the presence of the ss-DNA monolayer. Very few changes of ˜5×10-7 in the ss-DNA's refractive index result in valuable TMOKE response. We found that the presence of three-layer Gr and two-layer MoS2 on top of the Au/Py bilayer can dramatically increase the sensitivity by nine and four times, respectively, than the conventional Au/Co/Au trilayer. Our results show the highest reported DNA sensitivity based on the coupling of light with 2-D materials in magnetoplasmonic devices.

Identification of potential barriers to nurse-sensitive outcome demonstration.

PubMed

Beckel, Jean; Wolf, Gail; Wilson, Roxanne; Hoolahan, Susan

2013-12-01

The objective of this study was to determine differences in chief nursing officer, Magnet(®) program director, nurse leader, and direct care RN perspectives of potential barriers to demonstration of nurse-sensitive outcomes. The Magnet Recognition Program(®) and other designations are focusing on patient outcomes. No evidence is available addressing barriers to demonstration of nursing outcomes at multiple levels of practice. A Likert scale tool was developed and administered to 526 attendees at the 2012 national Magnet conference. Questions related to available resources, benchmarks, outcome demonstration process understanding, perception of value, and competing priorities. Significant perception differences by role were demonstrated related to available resources, competing priorities, and process understanding supporting demonstration of nurse-sensitive outcomes. No significant differences were identified related to benchmarks or perception of process value to the organization. This study provides new information demonstrating potential barriers to demonstration of nurse-sensitive outcomes differing by role. Opportunity exists to develop systems and processes to reduce perceived barriers among the nursing workforce.

Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus.

PubMed

Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C; Pasricha, Pankaj J; Li, Xingde; Yu, Shaoyong

2015-03-15

Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. Copyright © 2015 the American Physiological Society.

Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus

PubMed Central

Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C.; Pasricha, Pankaj J.; Li, Xingde

2015-01-01

Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. PMID:25591867

Omega-3 Eicosapentaenoic Acid Decreases CD133 Colon Cancer Stem-Like Cell Marker Expression While Increasing Sensitivity to Chemotherapy

PubMed Central

De Carlo, Flavia; Witte, Theodore R.; Hardman, W. Elaine; Claudio, Pier Paolo

2013-01-01

Colorectal cancer is the third leading cause of cancer-related death in the western world. In vitro and in vivo experiments showed that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can attenuate the proliferation of cancer cells, including colon cancer, and increase the efficacy of various anticancer drugs. However, these studies address the effects of n-3 PUFAs on the bulk of the tumor cells and not on the undifferentiated colon cancer stem-like cells (CSLCs) that are responsible for tumor formation and maintenance. CSLCs have also been linked to the acquisition of chemotherapy resistance and to tumor relapse. Colon CSLCs have been immunophenotyped using several antibodies against cellular markers including CD133, CD44, EpCAM, and ALDH. Anti-CD133 has been used to isolate a population of colon cancer cells that retains stem cells properties (CSLCs) from both established cell lines and primary cell cultures. We demonstrated that the n-3 PUFA, eicosapentaenoic acid (EPA), was actively incorporated into the membrane lipids of COLO 320 DM cells. 25 uM EPA decreased the cell number of the overall population of cancer cells, but not of the CD133 (+) CSLCs. Also, we observed that EPA induced down-regulation of CD133 expression and up-regulation of colonic epithelium differentiation markers, Cytokeratin 20 (CK20) and Mucin 2 (MUC2). Finally, we demonstrated that EPA increased the sensitivity of COLO 320 DM cells (total population) to both standard-of-care chemotherapies (5-Fluorouracil and oxaliplatin), whereas EPA increased the sensitivity of the CD133 (+) CSLCs to only 5-Fluorouracil. PMID:23874993

Characterization of peripheral and central sensitization after dorsal root ganglion intervention in patients with unilateral lumbosacral radicular pain: a prospective pilot study.

PubMed

Mehta, V; Snidvongs, S; Ghai, B; Langford, R; Wodehouse, T

2017-06-01

Quantitative sensory testing (QST) has been used to predict the outcome of epidural steroid injections in lumbosacral radicular pain and has the potential to be an important tool in the selection of appropriate treatment (such as epidural steroid injections vs surgery) for patients with chronic radicular pain. In addition, QST assists in identification of the pain pathways of peripheral and central sensitization in selected groups of patients. Twenty-three patients were given dorsal root ganglion (DRG) infiltration with local anaesthesia and steroid ('DRG block'), and those who demonstrated at least 50% pain relief were offered pulsed radiofrequency (PRF) to the DRG. Questionnaires and QST scores were measured before the DRG blocks and at 1 week and 3 months after their procedure. Those who received PRF also answered questionnaires and underwent QST measurements at 1 week and 3 months after their procedure. There was a significant increase in pressure pain threshold scores after DRG blocks. A reduced conditioned pain modulation response was seen before DRG, which increased after the procedure. Ten out of 23 patients underwent PRF to the DRG, and an increase in pressure pain threshold scores after PRF was observed. The conditioned pain modulation response was maintained in this group and increased after PRF. The study demonstrates that patients with unilateral radicular low back pain who receive dorsal root ganglion interventions show changes in pressure pain thresholds and conditioned pain modulation that are consistent with a 'normalization' of peripheral and central sensitization. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Effects of Radiation on the Microbiota and Intestinal Inflammatory Disease

DTIC Science & Technology

2017-09-01

microbial communities induced by intestinal radiation exposure. Currently, we demonstrate that these changes correlate with increased sensitivity to...Accomplishment: Place a description of the latest scientific accomplishment here. Limit the comments to three lines or less to make them fit; be succinct. These comments are valuable since they show progress.

Dual functions of YF3:Eu3+ for improving photovoltaic performance of dye-sensitized solar cells

PubMed Central

Wu, Jihuai; Wang, Jiangli; Lin, Jianming; Xiao, Yaoming; Yue, Gentian; Huang, Miaoliang; Lan, Zhang; Huang, Yunfang; Fan, Leqing; Yin, Shu; Sato, Tsugio

2013-01-01

In order to enhance the photovoltaic performance of dye-sensitized solar cell (DSSC), a novel design is demonstrated by introducing rare-earth compound europium ion doped yttrium fluoride (YF3:Eu3+) in TiO2 film in the DSSC. As a conversion luminescence medium, YF3:Eu3+ transfers ultraviolet light to visible light via down-conversion, and increases incident harvest and photocurrent of DSSC. As a p-type dopant, Eu3+ elevates the Fermi level of TiO2 film and thus heightens photovoltage of the DSSC. The conversion luminescence and p-type doping effect are demonstrated by photoluminescence spectra and Mott-Schottky plots. When the ratio of YF3:Eu3+/TiO2 in the doping layer is optimized as 5 wt.%, the light-to-electric energy conversion efficiency of the DSSC reaches 7.74%, which is increased by 32% compared to that of the DSSC without YF3:Eu3+ doping. Double functions of doped rare-earth compound provide a new route for enhancing the photovoltaic performance of solar cells. PMID:23792787

Decreased alertness due to sleep loss increases pain sensitivity in mice

PubMed Central

Alexandre, Chloe; Latremoliere, Alban; Ferreira, Ashley; Miracca, Giulia; Yamamoto, Mihoko; Scammell, Thomas E; Woolf, Clifford J

2018-01-01

Extended daytime and nighttime activities are major contributors to the growing sleep deficiency epidemic1,2, as is the high prevalence of sleep disorders like insomnia. The consequences of chronic insufficient sleep for health remain uncertain3. Sleep quality and duration predict presence of pain the next day in healthy subjects4–7, suggesting that sleep disturbances alone may worsen pain, and experimental sleep deprivation in humans supports this claim8,9. We demonstrate that sleep loss, but not sleep fragmentation, in healthy mice increases sensitivity to noxious stimuli (referred to as ‘pain’) without general sensory hyper-responsiveness. Moderate daily repeated sleep loss leads to a progressive accumulation of sleep debt and also to exaggerated pain responses, both of which are rescued after restoration of normal sleep. Caffeine and modafinil, two wake-promoting agents that have no analgesic activity in rested mice, immediately normalize pain sensitivity in sleep-deprived animals, without affecting sleep debt. The reversibility of mild sleep-loss-induced pain by wake-promoting agents reveals an unsuspected role for alertness in setting pain sensitivity. Clinically, insufficient or poor-quality sleep may worsen pain and this enhanced pain may be reduced not by analgesics, whose effectiveness is reduced, but by increasing alertness or providing better sleep. PMID:28481358

Increased imaging speed and force sensitivity for bio-applications with small cantilevers using a conventional AFM setup

PubMed Central

Leitner, Michael; Fantner, Georg E.; Fantner, Ernest J.; Ivanova, Katerina; Ivanov, Tzvetan; Rangelow, Ivo; Ebner, Andreas; Rangl, Martina; Tang, Jilin; Hinterdorfer, Peter

2012-01-01

In this study, we demonstrate the increased performance in speed and sensitivity achieved by the use of small AFM cantilevers on a standard AFM system. For this, small rectangular silicon oxynitride cantilevers were utilized to arrive at faster atomic force microscopy (AFM) imaging times and more sensitive molecular recognition force spectroscopy (MRFS) experiments. The cantilevers we used had lengths between 13 and 46 μm, a width of about 11 μm, and a thickness between 150 and 600 nm. They were coated with chromium and gold on the backside for a better laser reflection. We characterized these small cantilevers through their frequency spectrum and with electron microscopy. Due to their small size and high resonance frequency we were able to increase the imaging speed by a factor of 10 without any loss in resolution for images from several μm scansize down to the nanometer scale. This was shown on bacterial surface layers (s-layer) with tapping mode under aqueous, near physiological conditions and on nuclear membranes in contact mode in ambient environment. In addition, we showed that single molecular forces can be measured with an up to 5 times higher force sensitivity in comparison to conventional cantilevers with similar spring constants. PMID:22721963

Enhanced Enzyme-Linked Immunosorbent Assay for Detection of Antibodies to Virus-Like Particles of Human Papillomavirus

PubMed Central

Studentsov, Yevgeniy Y.; Schiffman, Mark; Strickler, Howard D.; Ho, Gloria Y. F.; Pang, Yuk-Ying Susana; Schiller, John; Herrero, Rolando; Burk, Robert D.

2002-01-01

Measurement of antibodies to human papillomavirus (HPV) is complicated by many factors. Although enzyme-linked immunosorbent assays (ELISAs) that use virus-like particles (VLPs) have proved useful, the assays have, in general, had moderate sensitivities and low signal-to-noise ratios. To enhance the performance of the assay, a systematic investigation was undertaken to examine key variables used in ELISAs for the detection of antibodies to VLPs of HPV. Incorporation of two vinyl polymers, polyvinyl alcohol (molecular weight, 50,000) (PVA-50) and polyvinylpyrrolidone (molecular weight, 360,000) (PVP-360), was found to increase the sensitivity as well as the specificity of the assay for the detection of antibodies to VLPs of HPV. In particular, the addition of PVA-50 to the blocking solution reduced the amount of nonspecific binding of antibodies to VLPs and the microplate surface, whereas the addition of PVP-360 increased the sensitivity of antibody detection. The new ELISA demonstrated increased sensitivity and specificity for the detection of cervical HPV type 16 infection compared to those of a prototype assay with coded clinical serum samples from women with known cervicovaginal HPV infection status. It is anticipated that the enhanced ELISA conditions will have wide application to a large number of clinical diagnostic assays. PMID:11980956

High sensitivity, high surface area Enzyme-linked Immunosorbent Assay (ELISA).

PubMed

Singh, Harpal; Morita, Takahiro; Suzuki, Yuma; Shimojima, Masayuki; Le Van, An; Sugamata, Masami; Yang, Ming

2015-01-01

Enzyme-linked immunosorbent assays (ELISA) are considered the gold standard in the demonstration of various immunological reactions with an application in the detection of infectious diseases such as during outbreaks or in patient care. This study aimed to produce an ELISA-based diagnostic with an increased sensitivity of detection compared to the standard 96-well method in the immunologic diagnosis of infectious diseases. A '3DStack' was developed using readily available, low cost fabrication technologies namely nanoimprinting and press stamping with an increased surface area of 4 to 6 times more compared to 96-well plates. This was achieved by stacking multiple nanoimprinted polymer sheets. The flow of analytes between the sheets was enhanced by rotating the 3DStack and confirmed by Finite-Element (FE) simulation. An Immunoglobulin G (IgG) ELISA for the detection of antibodies in human serum raised against Rubella virus was performed for validation. An improved sensitivity of up to 1.9 folds higher was observed using the 3DStack compared to the standard method. The increased surface area of the 3DStack developed using nanoimprinting and press stamping technologies, and the flow pattern between sheets generated by rotating the 3DStack were potential contributors to a more sensitive ELISA-based diagnostic device.

Upregulation of T-type Ca2+ channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons.

PubMed

Duzhyy, Dmytro E; Viatchenko-Karpinski, Viacheslav Y; Khomula, Eugen V; Voitenko, Nana V; Belan, Pavel V

2015-05-20

Previous studies have shown that increased excitability of capsaicin-sensitive DRG neurons and thermal hyperalgesia in rats with short-term (2-4 weeks) streptozotocin-induced diabetes is mediated by upregulation of T-type Ca(2+) current. In longer-term diabetes (after the 8th week) thermal hyperalgesia is changed to hypoalgesia that is accompanied by downregulation of T-type current in capsaicin-sensitive small-sized nociceptors. At the same time pain symptoms of diabetic neuropathy other than thermal persist in STZ-diabetic animals and patients during progression of diabetes into later stages suggesting that other types of DRG neurons may be sensitized and contribute to pain. In this study, we examined functional expression of T-type Ca(2+) channels in capsaicin-insensitive DRG neurons and excitability of these neurons in longer-term diabetic rats and in thermally hypoalgesic diabetic rats. Here we have demonstrated that in STZ-diabetes T-type current was upregulated in capsaicin-insensitive low-pH-sensitive small-sized nociceptive DRG neurons of longer-term diabetic rats and thermally hypoalgesic diabetic rats. This upregulation was not accompanied by significant changes in biophysical properties of T-type channels suggesting that a density of functionally active channels was increased. Sensitivity of T-type current to amiloride (1 mM) and low concentration of Ni(2+) (50 μM) implicates prevalence of Cav3.2 subtype of T-type channels in the capsaicin-insensitive low-pH-sensitive neurons of both naïve and diabetic rats. The upregulation of T-type channels resulted in the increased neuronal excitability of these nociceptive neurons revealed by a lower threshold for action potential initiation, prominent afterdepolarizing potentials and burst firing. Sodium current was not significantly changed in these neurons during long-term diabetes and could not contribute to the diabetes-induced increase of neuronal excitability. Capsaicin-insensitive low-pH-sensitive type of DRG neurons shows diabetes-induced upregulation of Cav3.2 subtype of T-type channels. This upregulation results in the increased excitability of these neurons and may contribute to nonthermal nociception at a later-stage diabetes.

The VP40 protein of Marburg virus exhibits impaired budding and increased sensitivity to human tetherin following mouse adaptation.

PubMed

Feagins, Alicia R; Basler, Christopher F

2014-12-01

The Marburg virus VP40 protein is a viral matrix protein that spontaneously buds from cells. It also functions as an interferon (IFN) signaling antagonist by targeting Janus kinase 1 (JAK1). A previous study demonstrated that the VP40 protein of the Ravn strain of Marburg virus (Ravn virus [RAVV]) failed to block IFN signaling in mouse cells, whereas the mouse-adapted RAVV (maRAVV) VP40 acquired the ability to inhibit IFN responses in mouse cells. The increased IFN antagonist function of maRAVV VP40 mapped to residues 57 and 165, which were mutated during the mouse adaptation process. In the present study, we demonstrate that maRAVV VP40 lost the capacity to efficiently bud from human cell lines, despite the fact that both parental and maRAVV VP40s bud efficiently from mouse cell lines. The impaired budding in human cells corresponds with the appearance of protrusions on the surface of maRAVV VP40-expressing Huh7 cells and with an increased sensitivity of maRAVV VP40 to restriction by human tetherin but not mouse tetherin. However, transfer of the human tetherin cytoplasmic tail to mouse tetherin restored restriction of maRAVV VP40. Residues 57 and 165 were demonstrated to contribute to the failure of maRAVV VP40 to bud from human cells, and residue 57 was demonstrated to alter VP40 oligomerization, as assessed by coprecipitation assay, and to determine sensitivity to human tetherin. This suggests that RAVV VP40 acquired, during adaptation to mice, changes in its oligomerization potential that enhanced IFN antagonist function. However, this new capacity impaired RAVV VP40 budding from human cells. Filoviruses, which include Marburg viruses and Ebola viruses, are zoonotic pathogens that cause severe disease in humans and nonhuman primates but do not cause similar disease in wild-type laboratory strains of mice unless first adapted to these animals. Although mouse adaptation has been used as a method to develop small animal models of pathogenesis, the molecular determinants associated with filovirus mouse adaptation are poorly understood. Our study demonstrates how genetic changes that accrued during mouse adaptation of the Ravn strain of Marburg virus have impacted the budding function of the viral VP40 matrix protein. Strikingly, we find impairment of mouse-adapted VP40 budding function in human but not mouse cell lines, and we correlate the impairment with an increased sensitivity of VP40 to restriction by human but not mouse tetherin and with changes in VP40 oligomerization. These data suggest that there are functional costs associated with filovirus adaptation to new hosts and implicate tetherin as a filovirus host restriction factor. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

High sensitive reflection type long period fiber grating biosensor for real time detection of thyroglobulin, a differentiated thyroid cancer biomarker: the Smart Health project

NASA Astrophysics Data System (ADS)

Quero, G.; Severino, R.; Vaiano, P.; Consales, M.; Ruvo, M.; Sandomenico, A.; Borriello, A.; Giordano, M.; Zuppolini, S.; Diodato, L.; Cutolo, A.; Cusano, A.

2015-09-01

We report the development of a reflection-type long period fiber grating (LPG) biosensor able to perform the real time detection of thyroid cancer markers in the needle washout of fine-needle aspiration biopsy. A standard LPG is first transformed in a practical probe working in reflection mode, then it is coated by an atactic-polystyrene overlay in order to increase its surrounding refractive index sensitivity and to provide, at the same time, the desired interfacial properties for a stable bioreceptor immobilization. The results provide a clear demonstration of the effectiveness and sensitivity of the developed biosensing platform, allowing the in vitro detection of human Thyroglobulin at sub-nanomolar concentrations.

Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems With Switching [Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems

DOE PAGES

Zhang, Hong; Abhyankar, Shrirang; Constantinescu, Emil; ...

2017-01-24

Sensitivity analysis is an important tool for describing power system dynamic behavior in response to parameter variations. It is a central component in preventive and corrective control applications. The existing approaches for sensitivity calculations, namely, finite-difference and forward sensitivity analysis, require a computational effort that increases linearly with the number of sensitivity parameters. In this paper, we investigate, implement, and test a discrete adjoint sensitivity approach whose computational effort is effectively independent of the number of sensitivity parameters. The proposed approach is highly efficient for calculating sensitivities of larger systems and is consistent, within machine precision, with the function whosemore » sensitivity we are seeking. This is an essential feature for use in optimization applications. Moreover, our approach includes a consistent treatment of systems with switching, such as dc exciters, by deriving and implementing the adjoint jump conditions that arise from state-dependent and time-dependent switchings. The accuracy and the computational efficiency of the proposed approach are demonstrated in comparison with the forward sensitivity analysis approach. In conclusion, this paper focuses primarily on the power system dynamics, but the approach is general and can be applied to hybrid dynamical systems in a broader range of fields.« less

Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems With Switching [Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems

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

Zhang, Hong; Abhyankar, Shrirang; Constantinescu, Emil

Sensitivity analysis is an important tool for describing power system dynamic behavior in response to parameter variations. It is a central component in preventive and corrective control applications. The existing approaches for sensitivity calculations, namely, finite-difference and forward sensitivity analysis, require a computational effort that increases linearly with the number of sensitivity parameters. In this paper, we investigate, implement, and test a discrete adjoint sensitivity approach whose computational effort is effectively independent of the number of sensitivity parameters. The proposed approach is highly efficient for calculating sensitivities of larger systems and is consistent, within machine precision, with the function whosemore » sensitivity we are seeking. This is an essential feature for use in optimization applications. Moreover, our approach includes a consistent treatment of systems with switching, such as dc exciters, by deriving and implementing the adjoint jump conditions that arise from state-dependent and time-dependent switchings. The accuracy and the computational efficiency of the proposed approach are demonstrated in comparison with the forward sensitivity analysis approach. In conclusion, this paper focuses primarily on the power system dynamics, but the approach is general and can be applied to hybrid dynamical systems in a broader range of fields.« less

The march from early life food sensitization to allergic disease: a systematic review and meta-analyses of birth cohort studies.

PubMed

Alduraywish, S A; Lodge, C J; Campbell, B; Allen, K J; Erbas, B; Lowe, A J; Dharmage, S C

2016-01-01

There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question. We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitization and allergic disease in birth cohorts. MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitization in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group. The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitization was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitization is related to an increased risk of wheeze/asthma (pooled OR 2.9; 95% CI 2.0-4.0), eczema (pooled OR 2.7; 95% CI 1.7-4.4) and allergic rhinitis (pooled OR 3.1; 95% CI 1.9-4.9) from 4 to 8 years. Food sensitization in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Temperature sensitivity and enzymatic mechanisms of soil organic matter decomposition along an altitudinal gradient on Mount Kilimanjaro

NASA Astrophysics Data System (ADS)

Blagodatskaya, Evgenia; Blagodatsky, Sergey; Khomyakov, Nikita; Myachina, Olga; Kuzyakov, Yakov

2016-02-01

Short-term acceleration of soil organic matter decomposition by increasing temperature conflicts with the thermal adaptation observed in long-term studies. Here we used the altitudinal gradient on Mt. Kilimanjaro to demonstrate the mechanisms of thermal adaptation of extra- and intracellular enzymes that hydrolyze cellulose, chitin and phytate and oxidize monomers (14C-glucose) in warm- and cold-climate soils. We revealed that no response of decomposition rate to temperature occurs because of a cancelling effect consisting in an increase in half-saturation constants (Km), which counteracts the increase in maximal reaction rates (Vmax with temperature). We used the parameters of enzyme kinetics to predict thresholds of substrate concentration (Scrit) below which decomposition rates will be insensitive to global warming. Increasing values of Scrit, and hence stronger canceling effects with increasing altitude on Mt. Kilimanjaro, explained the thermal adaptation of polymer decomposition. The reduction of the temperature sensitivity of Vmax along the altitudinal gradient contributed to thermal adaptation of both polymer and monomer degradation. Extrapolating the altitudinal gradient to the large-scale latitudinal gradient, these results show that the soils of cold climates with stronger and more frequent temperature variation are less sensitive to global warming than soils adapted to high temperatures.

A retrospective analysis of preoperative staging modalities for oral squamous cell carcinoma.

PubMed

Kähling, Ch; Langguth, T; Roller, F; Kroll, T; Krombach, G; Knitschke, M; Streckbein, Ph; Howaldt, H P; Wilbrand, J-F

2016-12-01

An accurate preoperative assessment of cervical lymph node status is a prerequisite for individually tailored cancer therapies in patients with oral squamous cell carcinoma. The detection of malignant spread and its treatment crucially influence the prognosis. The aim of the present study was to analyze the different staging modalities used among patients with a diagnosis of primary oral squamous cell carcinoma between 2008 and 2015. An analysis of preoperative staging findings, collected by clinical palpation, ultrasound, and computed tomography (CT), was performed. The results obtained were compared with the results of the final histopathological findings of the neck dissection specimens. A statistical analysis using McNemar's test was performed. The sensitivity of CT for the detection of malignant cervical tumor spread was 74.5%. The ultrasound obtained a sensitivity of 60.8%. Both CT and ultrasound demonstrated significantly enhanced sensitivity compared to the clinical palpation with a sensitivity of 37.1%. No significant difference was observed between CT and ultrasound. A combination of different staging modalities increased the sensitivity significantly compared with ultrasound staging alone. No significant difference in sensitivity was found between the combined use of different staging modalities and CT staging alone. The highest sensitivity, of 80.0%, was obtained by a combination of all three staging modalities: clinical palpation, ultrasound and CT. The present study indicates that CT has an essential role in the preoperative staging of patients with oral squamous cell carcinoma. Its use not only significantly increases the sensitivity of cervical lymph node metastasis detection but also offers a preoperative assessment of local tumor spread and resection borders. An additional non-invasive cervical lymph node examination increases the sensitivity of the tumor staging process and reduces the risk of occult metastasis. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response

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

Viel, Francis; Duzenli, Cheryl; British Columbia Cancer Agency, Department of Medical Physics, Vancouver Centre

2014-08-15

Introduction: Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA. Materials and Methods: Linac log file data andmore » a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate. Results: Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range. Conclusions: QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.« less

Angiotensin II modulates salty and sweet taste sensitivities.

PubMed

Shigemura, Noriatsu; Iwata, Shusuke; Yasumatsu, Keiko; Ohkuri, Tadahiro; Horio, Nao; Sanematsu, Keisuke; Yoshida, Ryusuke; Margolskee, Robert F; Ninomiya, Yuzo

2013-04-10

Understanding the mechanisms underlying gustatory detection of dietary sodium is important for the prevention and treatment of hypertension. Here, we show that Angiotensin II (AngII), a major mediator of body fluid and sodium homeostasis, modulates salty and sweet taste sensitivities, and that this modulation critically influences ingestive behaviors in mice. Gustatory nerve recording demonstrated that AngII suppressed amiloride-sensitive taste responses to NaCl. Surprisingly, AngII also enhanced nerve responses to sweeteners, but had no effect on responses to KCl, sour, bitter, or umami tastants. These effects of AngII on nerve responses were blocked by the angiotensin II type 1 receptor (AT1) antagonist CV11974. In behavioral tests, CV11974 treatment reduced the stimulated high licking rate to NaCl and sweeteners in water-restricted mice with elevated plasma AngII levels. In taste cells AT1 proteins were coexpressed with αENaC (epithelial sodium channel α-subunit, an amiloride-sensitive salt taste receptor) or T1r3 (a sweet taste receptor component). These results suggest that the taste organ is a peripheral target of AngII. The specific reduction of amiloride-sensitive salt taste sensitivity by AngII may contribute to increased sodium intake. Furthermore, AngII may contribute to increased energy intake by enhancing sweet responses. The linkage between salty and sweet preferences via AngII signaling may optimize sodium and calorie intakes.

Enhancing Effect of Continuous Cobalt-60 Gamma-Radiation on Susceptibility to Anaphylactic Shock in Mice

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

Hale, William M.; Stoner, Richard D.

1958-05-01

Continuous exposure to gamma -radiation at a dose rate of 4 rep/hr enhanced the severity of anaphylactnic shock ln mice sensitized with tetanus toxoid and challenged 1 hour or 7 days postradiation with fluid tetanus toxoid. A sharp increase in susceptibility to fatal anaphylaxis was observed as the accumulated dose was increased from 192 to 288 rep. Recovery from the enhancing effect of continuous gamma -radiation began during the second week postradiation; complete recovery occurred during the third week after an accumulated dose of 672 rep. Anaphylactic shock was demonstrable in mice sensitized 6 months before challenge with the specificmore » antigen. An enhanced susceptibility to fatal anaphylaxis was obtained when these animals were given an accumulated dose of 288 rep and challenged 1 hour postradiation. Passive anaphylaxis was more severe in irradiated mice sensitized with homopogous antitoxin 1 hour postradiation and challenged the following day with tetanus toxoid. The antihistaminic agent Thephorin afforded complete protection from fatal anaphypaxis in irradiated mice. (auth)« less

Allergic Potential and Immunotoxicity Induced by Topical Application of 1-Chloro-4-(Trifluoromethyl)Benzene (PCBTF) in a Murine Model

PubMed Central

Franko, Jennifer; Jackson, Laurel G.; Meade, B. Jean; Anderson, Stacey E.

2011-01-01

The purpose of the studies in this paper was to evaluate the allergic potential, immunotoxicity, and irritancy of the occupationally relevant chemical, 1-chloro-4-(trifluoromethyl)benzene, also known as parachlorobenzotrifluoride (PCBTF), following dermal exposure in a murine model. Evaluation of the sensitization potential, conducted using the local lymph node assay (LLNA) at concentrations ranging from 50% to 100%, identified a dose-dependent increase in lymphocyte proliferation with a calculated EC3 value of 53.1%. While no elevations in total or specific IgE were observed after exposure to any concentration of the chemical, significant increases in IFN-γ protein production by stimulated draining lymphoid cells were observed, indicating a T-cell-mediated response. Dermal exposure to PCBTF was not found to alter the immune response to a T-cell-dependant antigen. These results demonstrate that PCBTF has the potential to induce allergic sensitization following dermal exposure and based on LLNA results would be classified as a weak sensitizer. PMID:21747864

Design and experimental validation of Unilateral Linear Halbach magnet arrays for single-sided magnetic resonance.

PubMed

Bashyam, Ashvin; Li, Matthew; Cima, Michael J

2018-07-01

Single-sided NMR has the potential for broad utility and has found applications in healthcare, materials analysis, food quality assurance, and the oil and gas industry. These sensors require a remote, strong, uniform magnetic field to perform high sensitivity measurements. We demonstrate a new permanent magnet geometry, the Unilateral Linear Halbach, that combines design principles from "sweet-spot" and linear Halbach magnets to achieve this goal through more efficient use of magnetic flux. We perform sensitivity analysis using numerical simulations to produce a framework for Unilateral Linear Halbach design and assess tradeoffs between design parameters. Additionally, the use of hundreds of small, discrete magnets within the assembly allows for a tunable design, improved robustness to variability in magnetization strength, and increased safety during construction. Experimental validation using a prototype magnet shows close agreement with the simulated magnetic field. The Unilateral Linear Halbach magnet increases the sensitivity, portability, and versatility of single-sided NMR. Copyright © 2018 Elsevier Inc. All rights reserved.

Design and experimental validation of Unilateral Linear Halbach magnet arrays for single-sided magnetic resonance

NASA Astrophysics Data System (ADS)

Bashyam, Ashvin; Li, Matthew; Cima, Michael J.

2018-07-01

Single-sided NMR has the potential for broad utility and has found applications in healthcare, materials analysis, food quality assurance, and the oil and gas industry. These sensors require a remote, strong, uniform magnetic field to perform high sensitivity measurements. We demonstrate a new permanent magnet geometry, the Unilateral Linear Halbach, that combines design principles from "sweet-spot" and linear Halbach magnets to achieve this goal through more efficient use of magnetic flux. We perform sensitivity analysis using numerical simulations to produce a framework for Unilateral Linear Halbach design and assess tradeoffs between design parameters. Additionally, the use of hundreds of small, discrete magnets within the assembly allows for a tunable design, improved robustness to variability in magnetization strength, and increased safety during construction. Experimental validation using a prototype magnet shows close agreement with the simulated magnetic field. The Unilateral Linear Halbach magnet increases the sensitivity, portability, and versatility of single-sided NMR.

Prolonged effect of stress at weaning on the brain serotonin metabolism and sexuality of female rats.

PubMed

Tekes, K; Hantos, M; Gyenge, M; Karabélyos, Cs; Csaba, G

2006-12-01

Weanling female rats were stressed (by water and food deprivation for two days) and three months later the following indexes were studied: 5-HT and 5-HIAA levels in five brain regions, blood plasma and cerebrospinal fluid (CSF), sexual activity and nocistatin level of the plasma and CSF. The 5-HIAA content of hypothalamus and brainstem was significantly decreased (in the brainstem with one third) and in the striatum significantly increased. Plasma nocistatin level was significantly increased. Meyerson index and lordosis quotient were similar to control, but the estrus frequency almost doubled in the stressed animals. Much more defense reactions were observed in the stressed females during trials of mating. The results demonstrate that, 1) the perinatal period is not only sensitive to the remote-effects of stress but later could also be stress-sensitive critical periods, and 2) the continuously differentiating (e.g. bone marrow) cells are sensitive to late imprinting by stress, as well as to the brain and the sexual system.

Improving Light Harvesting in Dye-Sensitized Solar Cells Using Hybrid Bimetallic Nanostructures

DOE PAGES

Zarick, Holly F.; Erwin, William R.; Boulesbaa, Abdelaziz; ...

2016-01-25

In this paper, we demonstrate improved light trapping in dye-sensitized solar cells (DSSCs) with hybrid bimetallic gold core/silver shell nanostructures. Silica-coated bimetallic nanostructures (Au/Ag/SiO 2 NSs) integrated in the active layer of DSSCs resulted in 7.51% power conversion efficiency relative to 5.97% for reference DSSCs, giving rise to 26% enhancement in device performance. DSSC efficiencies were governed by the particle density of Au/Ag/SiO 2 NSs with best performing devices utilizing only 0.44 wt % of nanostructures. We performed transient absorption spectroscopy of DSSCs with variable concentrations of Au/Ag/SiO 2 NSs and observed an increase in amplitude and decrease in lifetimemore » with increasing particle density relative to reference. Finally, we attributed this trend to plasmon resonant energy transfer and population of the singlet excited states of the sensitizer molecules at the optimum concentration of NSs promoting enhanced exciton generation and rapid charge transfer into TiO 2.« less

Uteroplacental insufficiency temporally exacerbates salt-induced hypertension associated with a reduced natriuretic response in male rat offspring.

PubMed

Gallo, Linda A; Walton, Sarah L; Mazzuca, Marc Q; Tare, Marianne; Parkington, Helena C; Wlodek, Mary E; Moritz, Karen M

2018-03-31

Low weight at birth increases the risk of developing chronic diseases in adulthood A diet that is high in salt is known to elevate blood pressure, which is a major risk factor for cardiovascular and kidney diseases The present study demonstrates that growth restricted male rats have a heightened sensitivity to high dietary salt, in the context of raised systolic blood pressure, reduced urinary sodium excretion and stiffer mesenteric resistance vessels Other salt-induced effects, such as kidney hyperfiltration, albuminuria and glomerular damage, were not exacerbated by being born small The present study demonstrates that male offspring born small have an increased cardiovascular susceptibility to high dietary salt, such that that minimizing salt intake is probably of particular benefit to this at-risk population ABSTRACT: Intrauterine growth restriction increases the risk of developing chronic diseases in adulthood. Lifestyle factors, such as poor dietary choices, may elevate this risk. We determined whether being born small increases the sensitivity to a dietary salt challenge, in the context of hypertension, kidney disease and arterial stiffness. Bilateral uterine vessel ligation or sham surgery (offspring termed Restricted and Control, respectively) was performed on 18-day pregnant Wistar Kyoto rats. Male offspring were allocated to receive a diet high in salt (8% sodium chloride) or remain on standard rat chow (0.52% sodium chloride) from 20 to 26 weeks of age for 6 weeks. Systolic blood pressure (tail-cuff), renal function (24 h urine excretions) and vascular stiffness (pressure myography) were assessed. Restricted males were born 15% lighter than Controls and remained smaller throughout the study. Salt-induced hypertension was exacerbated in Restricted offspring, reaching a peak systolic pressure of ∼175 mmHg earlier than normal weight counterparts. The natriuretic response to high dietary salt in Restricted animals was less than in Controls and may explain the early rise in arterial pressure. Growth restricted males allocated to a high salt diet also had increased passive arterial stiffness of mesenteric resistance arteries. Other aspects of renal function, including salt-induced hyperfiltration, albuminuria and glomerular damage, were not exacerbated by uteroplacental insufficiency. The present study demonstrates that male offspring exposed to uteroplacental insufficiency and born small have an increased sensitivity to salt-induced hypertension and arterial remodelling. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Validation of a modified FRAX® tool for improving outpatient efficiency--part of the "Catch Before a Fall" initiative.

PubMed

Parker, Simon; Ciaccio, Maria; Cook, Erica; Davenport, Graham; Cooper, Alun; Grange, Simon; Smitham, Peter

2015-01-01

We have validated our touch-screen-modified FRAX® tool against the traditional healthcare professional-led questionnaire, demonstrating strong concordance between doctor- and patient-derived results. We will use this in outpatient clinics and general practice to increase our capture rate of at-risk patients, making valuable use of otherwise wasted patient waiting times. Outpatient clinics offer an opportunity to collect valuable health information from a captive population. We have previously developed a modified fracture risk assessment (FRAX®) tool, enabling patients to self-assess their osteoporotic fracture risk in a touch-screen computer format and demonstrated its acceptability with patients. We aim to validate the accuracy of our tool against the traditional questionnaire. Fifty patients over 50 years of age within the fracture clinic independently completed a paper equivalent of our touch-screen-modified FRAX® questionnaire. Responses were analysed against the traditional healthcare professional (HCP)-led questionnaire which was carried out afterwards. Correlation was assessed by sensitivity, specificity, Cohen's kappa statistic and Fisher's exact test for each potential FRAX® outcome of "treat", "measure BMD" and "lifestyle advice". Age range was 51-98 years. The FRAX® tool was completed by 88 % of patients; six patients lacked confidence in estimating either their height or weight. Following question adjustment according to patient response and feedback, our tool achieved >95 % sensitivity and specificity for the "treat" and "lifestyle advice" groups, and 79 % sensitivity and 100 % specificity in the "measure BMD" group. Cohen's kappa value ranged from 0.823 to 0.995 across all groups, demonstrating "very good" agreement for all. Fisher's exact test demonstrated significant concordance between doctor and patient decisions. Our modified tool provides a simple, accurate and reliable method for patients to self-report their own FRAX® score outside the clinical contact period, thus releasing the HCP from the time required to complete the questionnaire and potentially increasing our capture rate of at-risk patients.

Satellite remote sensing of H2SO4 aerosol using the 8- to 12-microns window region: Application to Mount Pinatubo

NASA Technical Reports Server (NTRS)

Ackerman, Steven A.; Strabala, Kathleen I.

1994-01-01

Monitoring stratospheric aerosols containing H2SO4 using the brightness temperature (BT) difference between 11 and 8.3 microns (BT(sub 8)-BT(sub 11)) spectral channels is demonstrated using theoretical calculations and satellite observations. Assuming an aqueous solution of 50% and 75% sulfuric acid, radiative transfer calculations indicate that over oceans an increase in the optical depth of the stratospheric aerosol results in an increase in BT(sub 8)-BT(sub 11). Theoretical simulations suggest that the technique is sensitive to visible optical depths greater than approximately 0.15. The simulations also demonstrate a lack of sensitivity to the particle size distribution. Changes in pre- and post-Pinatubo observations by the High-resolution Infrared Radiation Sounder 2 (HIRS2) on board the NOAA 10 are consistent with observed optical depth measurements and confirm the sensitivity of these channels to the presence of the aerosol. The technique is also applied to cold tropical convective clouds and desert regions where the signal, though evident, is less conclusive. Time series analysis is applied to the NOAA 10 and NOAA 12 combined BT(sub 8-BT(sub 11) observations to detect the periodicity of the spread of the volcanic aerosol. Over a region of the southern Pacific a 18- to 26-day period is present. Model simulations were conducted to demonstrate a trispectral with observations near 8, 11, and 12 microns. The trispectral approach has high potential in that the spectral signature of cirrus, water vapor, and H2SO4 aerosols are different. Observations from NOAA 10 and NOAA 11 are combined to demonstrate the capabilities of these infrared wavelengths of detecting the aerosol. The signal is clearly evident when a region of the South Atlantic is compared for pre- and post-Pinatubo conditions.

Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells

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

Lopez, Veronica; Saraff, Kumuda; Medh, Jheem D., E-mail: jheem.medh@csun.edu

2009-11-06

Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-{gamma}) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-{gamma} activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-{gamma} in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted inmore » a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.« less

Palmitate stimulates glucose transport in rat adipocytes by a mechanism involving translocation of the insulin sensitive glucose transporter (GLUT4)

NASA Technical Reports Server (NTRS)

Hardy, R. W.; Ladenson, J. H.; Henriksen, E. J.; Holloszy, J. O.; McDonald, J. M.

1991-01-01

In rat adipocytes, palmitate: a) increases basal 2-deoxyglucose transport 129 +/- 27% (p less than 0.02), b) decreases the insulin sensitive glucose transporter (GLUT4) in low density microsomes and increases GLUT4 in plasma membranes and c) increases the activity of the insulin receptor tyrosine kinase. Palmitate-stimulated glucose transport is not additive with the effect of insulin and is not inhibited by the protein kinase C inhibitors staurosporine and sphingosine. In rat muscle, palmitate: a) does not affect basal glucose transport in either the soleus or epitrochlearis and b) inhibits insulin-stimulated glucose transport by 28% (p less than 0.005) in soleus but not in epitrochlearis muscle. These studies demonstrate a potentially important differential role for fatty acids in the regulation of glucose transport in different insulin target tissues.

Substance P enhances the activation of AMPK and cellular lipid accumulation in 3T3‑L1 cells in response to high levels of glucose.

PubMed

Dubon, Maria Jose; Byeon, Yeji; Park, Ki-Sook

2015-12-01

The rescue of glucose tolerance and insulin‑sensitivity in peripheral tissues, including adipose tissue, is essential in therapeutic strategies for diabetes. The present study demonstrated that substance P (SP) increases the accumulation of lipids in 3T3‑L1 cells during their differentiation into adipocytes in response to a high concentration of glucose. SP reciprocally regulated the activities of AMP‑activated protein kinase (AMPK) and Akt: SP enhanced the activation of AMPK, although the activity of Akt was downregulated. Notably, SP induced an increase in the expression level of glucose transporter 4 in the 3T3‑L1 adipocytes. Therefore, it is possible that SP leads to an increase in glucose uptake and the accumulation of lipids in adipocytes, and may contribute towards the rescue of insulin‑sensitivity in diabetes.

Mechanical Structural Design of a MEMS-Based Piezoresistive Accelerometer for Head Injuries Monitoring: A Computational Analysis by Increments of the Sensor Mass Moment of Inertia †

PubMed Central

Messina, Marco; Njuguna, James; Palas, Chrysovalantis

2018-01-01

This work focuses on the proof-mass mechanical structural design improvement of a tri-axial piezoresistive accelerometer specifically designed for head injuries monitoring where medium-G impacts are common; for example, in sports such as racing cars or American Football. The device requires the highest sensitivity achievable with a single proof-mass approach, and a very low error (<1%) as the accuracy for these types of applications is paramount. The optimization method differs from previous work as it is based on the progressive increment of the sensor proof-mass mass moment of inertia (MMI) in all three axes. Three different designs are presented in this study, where at each step of design evolution, the MMI of the sensor proof-mass gradually increases in all axes. The work numerically demonstrates that an increment of MMI determines an increment of device sensitivity with a simultaneous reduction of cross-axis sensitivity in the particular axis under study. This is due to the linkage between the external applied stress and the distribution of mass (of the proof-mass), and therefore of its mass moment of inertia. Progressively concentrating the mass on the axes where the piezoresistors are located (i.e., x- and y-axis) by increasing the MMI in the x- and y-axis, will undoubtedly increase the longitudinal stresses applied in that areas for a given external acceleration, therefore increasing the piezoresistors fractional resistance change and eventually positively affecting the sensor sensitivity. The final device shows a sensitivity increase of about 80% in the z-axis and a reduction of cross-axis sensitivity of 18% respect to state-of-art sensors available in the literature from a previous work of the authors. Sensor design, modelling, and optimization are presented, concluding the work with results, discussion, and conclusion. PMID:29351221

Interventional MRI: tapering improves the distal sensitivity of the loopless antenna.

PubMed

Qian, Di; El-Sharkawy, AbdEl-Monem M; Atalar, Ergin; Bottomley, Paul A

2010-03-01

The "loopless antenna" is an interventional MRI detector consisting of a tuned coaxial cable and an extended inner conductor or "whip". A limitation is the poor sensitivity afforded at, and immediately proximal to, its distal end, which is exacerbated by the extended whip length when the whip is uniformly insulated. It is shown here that tapered insulation dramatically improves the distal sensitivity of the loopless antenna by pushing the current sensitivity toward the tip. The absolute signal-to-noise ratio is numerically computed by the electromagnetic method-of-moments for three resonant 3-T antennae with no insulation, uniform insulation, and with linearly tapered insulation. The analysis shows that tapered insulation provides an approximately 400% increase in signal-to-noise ratio in trans-axial planes 1 cm from the tip and a 16-fold increase in the sensitive area as compared to an equivalent, uniformly insulated antenna. These findings are directly confirmed by phantom experiments and by MRI of an aorta specimen. The results demonstrate that numerical electromagnetic signal-to-noise ratio analysis can accurately predict the loopless detector's signal-to-noise ratio and play a central role in optimizing its design. The manifold improvement in distal signal-to-noise ratio afforded by redistributing the insulation should improve the loopless antenna's utility for interventional MRI. (c) 2010 Wiley-Liss, Inc.

Sensitivity of water resources in the Delaware River basin to climate variability and change

USGS Publications Warehouse

Ayers, Mark A.; Wolock, David M.; McCabe, Gregory J.; Hay, Lauren E.; Tasker, Gary D.

1993-01-01

Because of the "greenhouse effect," projected increases in atmospheric carbon dioxide levels might cause global warming, which in turn could result in changes in precipitation patterns and evapotranspiration and in increases in sea level. This report describes the greenhouse effect; discusses the problems and uncertainties associated with the detection, prediction, and effects of climatic change, and presents the results of sensitivity-analysis studies of the potential effects of climate change on water resources in the Delaware River basin. On the basis of sensitivity analyses, potentially serious shortfalls of certain water resources in the basin could result if some climatic-change scenarios become true. The results of basin streamflow-model simulations in this study demonstrate the difficulty in distinguishing effects of climatic change on streamflow and water supply from effects of natural variability in current climate. The future direction of basin changes in most water resources, furthermore, cannot be determined precisely because of uncertainty in current projections of regional temperature and precipitation. This large uncertainty indicates that, for resource planning, information defining the sensitivities of water resources to a range of climate change is most relevant. The sensitivity analyses could be useful in developing contingency plans on how to evaluate and respond to changes, should they occur.

Design and numerical analysis of highly sensitive Au-MoS2-graphene based hybrid surface plasmon resonance biosensor

NASA Astrophysics Data System (ADS)

Rahman, M. Saifur; Anower, Md. Shamim; Hasan, Md. Rabiul; Hossain, Md. Biplob; Haque, Md. Ismail

2017-08-01

We demonstrate a highly sensitive Au-MoS2-Graphene based hybrid surface plasmon resonance (SPR) biosensor for the detection of DNA hybridization. The performance parameters of the proposed sensor are investigated in terms of sensitivity, detection accuracy and quality factor at operating wavelength of 633 nm. We observed in the numerical study that sensitivity can be greatly increased by adding MoS2 layer in the middle of a Graphene-on-Au layer. It is shown that by using single layer of MoS2 in between gold and graphene layer, the proposed biosensor exhibits simultaneously high sensitivity of 87.8 deg/RIU, high detection accuracy of 1.28 and quality factor of 17.56 with gold layer thickness of 50 nm. This increased performance is due to the absorption ability and optical characteristics of graphene biomolecules and high fluorescence quenching ability of MoS2. On the basis of changing in SPR angle and minimum reflectance, the proposed sensor can sense nucleotides bonding happened between double-stranded DNA (dsDNA) helix structures. Therefore, this sensor can successfully detect the hybridization of target DNAs to the probe DNAs pre-immobilized on the Au-MoS2-Graphene hybrid with capability of distinguishing single-base mismatch.

Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

NASA Technical Reports Server (NTRS)

Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

2003-01-01

Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

Co-integrating plasmonics with Si3N4 photonics towards a generic CMOS compatible PIC platform for high-sensitivity multi-channel biosensors: the H2020 PlasmoFab approach (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tsiokos, Dimitris M.; Dabos, George; Ketzaki, Dimitra; Weeber, Jean-Claude; Markey, Laurent; Dereux, Alain; Giesecke, Anna Lena; Porschatis, Caroline; Chmielak, Bartos; Wahlbrink, Thorsten; Rochracher, Karl; Pleros, Nikos

2017-05-01

Silicon photonics meet most fabrication requirements of standard CMOS process lines encompassing the photonics-electronics consolidation vision. Despite this remarkable progress, further miniaturization of PICs for common integration with electronics and for increasing PIC functional density is bounded by the inherent diffraction limit of light imposed by optical waveguides. Instead, Surface Plasmon Polariton (SPP) waveguides can guide light at sub-wavelength scales at the metal surface providing unique light-matter interaction properties, exploiting at the same time their metallic nature to naturally integrate with electronics in high-performance ASPICs. In this article, we demonstrate the main goals of the recently introduced H2020 project PlasmoFab towards addressing the ever increasing needs for low energy, small size and high performance mass manufactured PICs by developing a revolutionary yet CMOS-compatible fabrication platform for seamless co-integration of plasmonics with photonic and supporting electronic. We demonstrate recent advances on the hosting SiN photonic hosting platform reporting on low-loss passive SiN waveguide and Grating Coupler circuits for both the TM and TE polarization states. We also present experimental results of plasmonic gold thin-film and hybrid slot waveguide configurations that can allow for high-sensitivity sensing, providing also the ongoing activities towards replacing gold with Cu, Al or TiN metal in order to yield the same functionality over a CMOS metallic structure. Finally, the first experimental results on the co-integrated SiN+plasmonic platform are demonstrated, concluding to an initial theoretical performance analysis of the CMOS plasmo-photonic biosensor that has the potential to allow for sensitivities beyond 150000nm/RIU.

Improvement of a PCR test to diagnose infection by Mansonella ozzardi.

PubMed

Vera, Luana Janaína Souza; Basano, Sergio de Almeida; Camargo, Juliana de Souza Almeida Aranha; França, Andonai Krauze de; Ferreira, Ricardo de Godoi Mattos; Casseb, Almeida Andrade; Medeiros, Jansen Fernandes; Fontes, Gilberto; Camargo, Luís Marcelo Aranha

2011-01-01

Mansonelliasis is caused by Mansonella ozzardi. It is widespread in the Amazon region, with a high prevalence. The common exam of thick blood smears stained with Giemsa shows low efficacy levels and has been an obstacle to diagnosing individuals with low blood parasitemia. In order to increase diagnosis efficacy, the PCR technique was improved. PCR demonstrated the best performance, with sensitivity and negative predictive values (NPV) of 100%, followed by blood filtration through membrane filters, which showed a sensitivity of 88.9% and a NPV of 84.6%, when compared to thick blood smears.

Small-displacement sensing system based on multiple total internal reflections in heterodyne interferometry.

PubMed

Wang, Shinn-Fwu; Chiu, Ming-Hung; Chen, Wei-Wu; Kao, Fu-Hsi; Chang, Rong-Seng

2009-05-01

A small-displacement sensing system based on multiple total internal reflections in heterodyne interferometry is proposed. In this paper, a small displacement can be obtained only by measuring the variation in phase difference between s- and p-polarization states for the total internal reflection effect. In order to improve the sensitivity, we increase the number of total internal reflections by using a parallelogram prism. The theoretical resolution of the method is better than 0.417 nm. The method has some merits, e.g., high resolution, high sensitivity, and real-time measurement. Also, its feasibility is demonstrated.

Fiber Bragg grating cryogenic temperature sensors

NASA Astrophysics Data System (ADS)

Gupta, Sanjay; Mizunami, Toru; Yamao, Takashi; Shimomura, Teruo

1996-09-01

Temperature sensing to as low as 80 K was demonstrated with 1.55- mu m fiber Bragg gratings. The gratings were bonded on substrates to increase sensitivity, and a shift of the reflection wavelength was measured. The temperature sensitivity was 0.02 nm/K at 100 K when an aluminum substrate was used and 0.04 nm/K at 100 K when a poly(methyl methacrylate) substrate was used. These values are smaller than those at room temperature because of the nonlinearity of both the thermal expansion and the thermo-optic effect. Extension to the liquid helium temperature is also discussed.

Non-enzymatic glucose detection based on phenylboronic acid modified optical fibers

NASA Astrophysics Data System (ADS)

Sun, Xiaolan; Li, Nana; Zhou, Bin; Zhao, Wei; Liu, Liyuan; Huang, Chao; Ma, Longfei; Kost, Alan R.

2018-06-01

A non-enzymatic, sensitive glucose sensor was fabricated based on an evanescent wave absorbing optical fiber probe. The optical fiber sensor was functionalized by fixing a poly (phenylboronic acid) (polyPBA) film onto the conical region of the single mode fiber. The reflected light intensity of the polyPBA-functionalized fiber sensor increased proportionally with glucose concentration in the range of 0-60 mM, and the sensor showed good reproducibility and stability. The developed sensor possessed a high sensitivity of 0.1787%/mM and good linearity. The measurement of glucose concentration in human serum was also demonstrated.

On vibrational imperfection sensitivity of Augusti's model structure in the vicinity of a non-linear static state

NASA Technical Reports Server (NTRS)

Elishakoff, Isaac; Marcus, S.; Starnes, J. H., JR.

1998-01-01

In this paper we present a closed-form solution for vibrational imperfection sensitivity the effect of small imperfections on the vibrational frequencies of perturbed motion around the static equilibrium state of Augusti's model Structure (a rigid link, pinned at one end to a rigid foundation and supported at the other by a linear extensional spring that retains its horizontality, as the system deflects). We also treat a modified version of that model with attendant slightly different dynamics. It is demonstrated that the vibrational frequencies decreases as the initial imperfections increase.

Tuning the physical properties of organic sensitizers by replacing triphenylamine with new donors for dye sensitized solar cells - a theoretical approach.

PubMed

Ramkumar, Sekar; Manidurai, Paulraj

2017-02-15

New donor molecules with low ionization potential have been theoretically designed by replacing the benzene moieties in triphenylamine (TPA) with thiophene as well as furan. The designed new donors also exhibited planar structure, making an angle of 120° around the nitrogen atom that results in resonance effects through π-bonds of aryl rings. New sensitizers have been theoretically studied using DFT and TD-DFT by adopting these designed donors. UV-Vis absorption spectra, light harvesting ability (LHE) and electron injection ability (ΔG inject ) of the designed sensitizers have been calculated by taking L0 as reference. Orbital overlapping between donor and acceptor facilitates intra-molecular charge transfer, thereby increasing the interfacial electron injection from the sensitizer to the semiconductor nanoparticles. Our theoretical results demonstrate that sensitizers DTPA-AA and DFPA-AA have broader absorption and lower ΔG inject respectively compare to L0, this opens a new way for designing sensitizers for dye sensitized solar cells (DSSCs). All the dyes designed were found to be good light harvesters. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced biosensing resolution with foundry fabricated individually addressable dual-gated ISFETs.

PubMed

Duarte-Guevara, Carlos; Lai, Fei-Lung; Cheng, Chun-Wen; Reddy, Bobby; Salm, Eric; Swaminathan, Vikhram; Tsui, Ying-Kit; Tuan, Hsiao Chin; Kalnitsky, Alex; Liu, Yi-Shao; Bashir, Rashid

2014-08-19

The adaptation of semiconductor technologies for biological applications may lead to a new era of inexpensive, sensitive, and portable diagnostics. At the core of these developing technologies is the ion-sensitive field-effect transistor (ISFET), a biochemical to electrical transducer with seamless integration to electronic systems. We present a novel structure for a true dual-gated ISFET that is fabricated with a silicon-on-insulator (SOI) complementary metal-oxide-semiconductor process by Taiwan Semiconductor Manufacturing Company (TSMC). In contrast to conventional SOI ISFETs, each transistor has an individually addressable back-gate and a gate oxide that is directly exposed to the solution. The elimination of the commonly used floating gate architecture reduces the chance of electrostatic discharge and increases the potential achievable transistor density. We show that when operated in a "dual-gate" mode, the transistor response can exhibit sensitivities to pH changes beyond the Nernst limit. This enhancement in sensitivity was shown to increase the sensor's signal-to-noise ratio, allowing the device to resolve smaller pH changes. An improved resolution can be used to enhance small signals and increase the sensor accuracy when monitoring small pH dynamics in biological reactions. As a proof of concept, we demonstrate that the amplified sensitivity and improved resolution result in a shorter detection time and a larger output signal of a loop-mediated isothermal DNA amplification reaction (LAMP) targeting a pathogenic bacteria gene, showing benefits of the new structure for biosensing applications.

Graphene-Based Long-Period Fiber Grating Surface Plasmon Resonance Sensor for High-Sensitivity Gas Sensing

PubMed Central

Wei, Wei; Nong, Jinpeng; Zhang, Guiwen; Tang, Linlong; Jiang, Xiao; Chen, Na; Luo, Suqin; Lan, Guilian; Zhu, Yong

2016-01-01

A graphene-based long-period fiber grating (LPFG) surface plasmon resonance (SPR) sensor is proposed. A monolayer of graphene is coated onto the Ag film surface of the LPFG SPR sensor, which increases the intensity of the evanescent field on the surface of the fiber and thereby enhances the interaction between the SPR wave and molecules. Such features significantly improve the sensitivity of the sensor. The experimental results demonstrate that the sensitivity of the graphene-based LPFG SPR sensor can reach 0.344 nm%−1 for methane, which is improved 2.96 and 1.31 times with respect to the traditional LPFG sensor and Ag-coated LPFG SPR sensor, respectively. Meanwhile, the graphene-based LPFG SPR sensor exhibits excellent response characteristics and repeatability. Such a SPR sensing scheme offers a promising platform to achieve high sensitivity for gas-sensing applications. PMID:28025483

Performance evaluation of a lossy transmission lines based diode detector at cryogenic temperature.

PubMed

Villa, E; Aja, B; de la Fuente, L; Artal, E

2016-01-01

This work is focused on the design, fabrication, and performance analysis of a square-law Schottky diode detector based on lossy transmission lines working under cryogenic temperature (15 K). The design analysis of a microwave detector, based on a planar gallium-arsenide low effective Schottky barrier height diode, is reported, which is aimed for achieving large input return loss as well as flat sensitivity versus frequency. The designed circuit demonstrates good sensitivity, as well as a good return loss in a wide bandwidth at Ka-band, at both room (300 K) and cryogenic (15 K) temperatures. A good sensitivity of 1000 mV/mW and input return loss better than 12 dB have been achieved when it works as a zero-bias Schottky diode detector at room temperature, increasing the sensitivity up to a minimum of 2200 mV/mW, with the need of a DC bias current, at cryogenic temperature.

Nano strain-amplifier: Making ultra-sensitive piezoresistance in nanowires possible without the need of quantum and surface charge effects

NASA Astrophysics Data System (ADS)

Phan, Hoang-Phuong; Dinh, Toan; Kozeki, Takahiro; Nguyen, Tuan-Khoa; Qamar, Afzaal; Namazu, Takahiro; Nguyen, Nam-Trung; Dao, Dzung Viet

2016-09-01

This paper presents an innovative nano strain-amplifier employed to significantly enhance the sensitivity of piezoresistive strain sensors. Inspired from the dogbone structure, the nano strain-amplifier consists of a nano thin frame released from the substrate, where nanowires were formed at the centre of the frame. Analytical and numerical results indicated that a nano strain-amplifier significantly increases the strain induced into a free standing nanowire, resulting in a large change in their electrical conductance. The proposed structure was demonstrated in p-type cubic silicon carbide nanowires fabricated using a top down process. The experimental data showed that the nano strain-amplifier can enhance the sensitivity of SiC strain sensors at least 5.4 times larger than that of the conventional structures. This result indicates the potential of the proposed strain-amplifier for ultra-sensitive mechanical sensing applications.

On the differentiation of N2 components in an appetitive choice task: evidence for the revised Reinforcement Sensitivity Theory.

PubMed

Leue, Anja; Chavanon, Mira-Lynn; Wacker, Jan; Stemmler, Gerhard

2009-11-01

Task- and personality-related modulations of the N2 were probed within the framework of the revised Reinforcement Sensitivity Theory (RST). Using an appetitive choice task, we investigated 58 students with extreme scores on the behavioral inhibition system and behavioral approach system (BIS/BAS) scales. The baseline-to-peak N2 amplitude was sensitive to the strength of decision conflict and demonstrated RST-related personality differences. In addition to the baseline N2 amplitude, temporal PCA results suggested two N2 components accounting for a laterality effect and capturing different N2 patterns for BIS/BAS groups with increasing conflict level. Evidence for RST-related personality differences was obtained for baseline-to-peak N2 and tPCA components in the present task. The results support the RST prediction that BAS sensitivity modulates conflict processing and confirm the cognitive-motivational conflict concept of RST.

A Novel Piezoresistive Accelerometer with SPBs to Improve the Tradeoff between the Sensitivity and the Resonant Frequency

PubMed Central

Xu, Yu; Zhao, Libo; Jiang, Zhuangde; Ding, Jianjun; Peng, Niancai; Zhao, Yulong

2016-01-01

For improving the tradeoff between the sensitivity and the resonant frequency of piezoresistive accelerometers, the dependency between the stress of the piezoresistor and the displacement of the structure is taken into consideration in this paper. In order to weaken the dependency, a novel structure with suspended piezoresistive beams (SPBs) is designed, and a theoretical model is established for calculating the location of SPBs, the stress of SPBs and the resonant frequency of the whole structure. Finite element method (FEM) simulations, comparative simulations and experiments are carried out to verify the good agreement with the theoretical model. It is demonstrated that increasing the sensitivity greatly without sacrificing the resonant frequency is possible in the piezoresistive accelerometer design. Therefore, the proposed structure with SPBs is potentially a novel option for improving the tradeoff between the sensitivity and the resonant frequency of piezoresistive accelerometers. PMID:26861343

A Novel Piezoresistive Accelerometer with SPBs to Improve the Tradeoff between the Sensitivity and the Resonant Frequency.

PubMed

Xu, Yu; Zhao, Libo; Jiang, Zhuangde; Ding, Jianjun; Peng, Niancai; Zhao, Yulong

2016-02-06

For improving the tradeoff between the sensitivity and the resonant frequency of piezoresistive accelerometers, the dependency between the stress of the piezoresistor and the displacement of the structure is taken into consideration in this paper. In order to weaken the dependency, a novel structure with suspended piezoresistive beams (SPBs) is designed, and a theoretical model is established for calculating the location of SPBs, the stress of SPBs and the resonant frequency of the whole structure. Finite element method (FEM) simulations, comparative simulations and experiments are carried out to verify the good agreement with the theoretical model. It is demonstrated that increasing the sensitivity greatly without sacrificing the resonant frequency is possible in the piezoresistive accelerometer design. Therefore, the proposed structure with SPBs is potentially a novel option for improving the tradeoff between the sensitivity and the resonant frequency of piezoresistive accelerometers.

Sensitivity Enhancement in Low Cutoff Wavelength Long-Period Fiber Gratings by Cladding Diameter Reduction.

PubMed

Del Villar, Ignacio; Partridge, Matthew; Rodriguez, Wenceslao Eduardo; Fuentes, Omar; Socorro, Abian Bentor; Diaz, Silvia; Corres, Jesus Maria; James, Stephen Wayne; Tatam, Ralph Peter

2017-09-13

The diameter of long-period fiber gratings (LPFGs) fabricated in optical fibers with a low cutoff wavelength was be reduced by hydrofluoric acid etching, enhancing the sensitivity to refractive index by more than a factor of 3, to 2611 nm/refractive index unit in the range from 1.333 to 1.4278. The grating period selected for the LPFGs allowed access to the dispersion turning point at wavelengths close to the visible range of the optical spectrum, where optical equipment is less expensive. As an example of an application, a pH sensor based on the deposition of a polymeric coating was analyzed in two situations: with an LPFG without diameter reduction and with an LPFG with diameter reduction. Again, a sensitivity increase of a factor of near 3 was obtained, demonstrating the ability of this method to enhance the sensitivity of thin-film-coated LPFG chemical sensors.

Dark matter sensitivity of multi-ton liquid xenon detectors

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

Schumann, Marc; Bütikofer, Lukas; Baudis, Laura

2015-10-01

We study the sensitivity of multi ton-scale time projection chambers using a liquid xenon target, e.g., the proposed DARWIN instrument, to spin-independent and spin-dependent WIMP-nucleon scattering interactions. Taking into account realistic backgrounds from the detector itself as well as from neutrinos, we examine the impact of exposure, energy threshold, background rejection efficiency and energy resolution on the dark matter sensitivity. With an exposure of 200 t × y and assuming detector parameters which have been already demonstrated experimentally, spin-independent cross sections as low as 2.5 × 10{sup −49} cm{sup 2} can be probed for WIMP masses around 40 GeV/c{sup 2}. Additional improvementsmore » in terms of background rejection and exposure will further increase the sensitivity, while the ultimate WIMP science reach will be limited by neutrinos scattering coherently off the xenon nuclei.« less

Teaching ethics in psychiatry: a one-day workshop for clinical students.

PubMed Central

Green, B; Miller, P D; Routh, C P

1995-01-01

In this paper we describe the objectives of teaching medical ethics to undergraduates and the teaching methods used. We describe a workshop used in the University of Liverpool Department of Psychiatry, designed to enhance ethical sensitivity in psychiatry. The workshop reviews significant historical and current errors in the ethical practice of psychiatry and doctors' defence mechanisms against accepting responsibility for deficiencies in ethical practice. The workshop explores the student doctors' own group ethos in response to ethical dilemmas, and demonstrates how the individual contributes to and is responsible for the group ethos through participation and also through nonparticipation. The student feedback about the workshop is reviewed. The Toronto Ethical Sensitivity Instrument was used to assess whether or not the workshop altered sensitivity. Compared to a control group the attenders' sensitivity was significantly increased (on Student's t-test p equals or is less than 0.002). PMID:7473644

Laser ablation surface-enhanced Raman microspectroscopy.

PubMed

Londero, Pablo S; Lombardi, John R; Leona, Marco

2013-06-04

Improved identification of trace organic compounds in complex matrixes is critical for a variety of fields such as material science, heritage science, and forensics. Surface-enhanced Raman scattering (SERS) is a vibrational spectroscopy technique that can attain single-molecule sensitivity and has been shown to complement mass spectrometry, but lacks widespread application without a robust method that utilizes the effect. We demonstrate a new, highly sensitive, and widely applicable approach to SERS analysis based on laser ablation in the presence of a tailored plasmonic substrate. We analyze several challenging compounds, including non-water-soluble pigments and dyed leather from an ancient Egyptian chariot, achieving sensitivity as high as 120 amol for a 1:1 signal-to-noise ratio and 5 μm spatial resolution. This represents orders of magnitude improvement in spatial resolution and sensitivity compared to those of other SERS approaches intended for widespread application, greatly increasing the applicability of SERS.

Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells.

PubMed

Kievit, Paul; Howard, Jane K; Badman, Michael K; Balthasar, Nina; Coppari, Roberto; Mori, Hiroyuki; Lee, Charlotte E; Elmquist, Joel K; Yoshimura, Akihiko; Flier, Jeffrey S

2006-08-01

Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

Sensitivity-Bandwidth Limit in a Multimode Optoelectromechanical Transducer

NASA Astrophysics Data System (ADS)

Moaddel Haghighi, I.; Malossi, N.; Natali, R.; Di Giuseppe, G.; Vitali, D.

2018-03-01

An optoelectromechanical system formed by a nanomembrane capacitively coupled to an L C resonator and to an optical interferometer has recently been employed for the highly sensitive optical readout of rf signals [T. Bagci et al., Nature (London) 507, 81 (2013), 10.1038/nature13029]. We propose and experimentally demonstrate how the bandwidth of such a transducer can be increased by controlling the interference between two electromechanical interaction pathways of a two-mode mechanical system. With a proof-of-principle device operating at room temperature, we achieve a sensitivity of 300 nV /√{Hz } over a bandwidth of 15 kHz in the presence of radio-frequency noise, and an optimal shot-noise-limited sensitivity of 10 nV /√{Hz } over a bandwidth of 5 kHz. We discuss strategies for improving the performance of the device, showing that, for the same given sensitivity, a mechanical multimode transducer can achieve a bandwidth significantly larger than that for a single-mode one.

Making your skin crawl: The role of tactile sensitivity in disease avoidance.

PubMed

Hunt, David Francis; Cannell, Grace; Davenhill, Nicholas A; Horsford, Stephanie A; Fleischman, Diana S; Park, Justin H

2017-07-01

Mounting evidence indicates that animals, including humans, have evolved a behavioral disease-avoidance system designed to facilitate the detection and avoidance of sources of pathogens, and that this system interacts with physiological defenses. The skin acts as an important anatomical barrier, yet little research has investigated the role of tactile sensitivity in disease avoidance. Increased tactile sensitivity in the presence of potential sources of pathogens may facilitate prophylactic behaviors such as self-grooming. Across multiple studies, we tested the hypothesis that the induction of disgust-the key emotion underlying disease avoidance-may lead to greater tactile sensitivity compared to control conditions. A nonsignificant trend was found in a pilot study, which was replicated (and found to be significant) in Studies 1 and 2. To our knowledge, these results are the first to demonstrate disgust-induced changes in tactile sensitivity, and they contribute to the growing literature on the integrated evolved defenses against infectious disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Smad4 loss promotes lung cancer formation but increases sensitivity to DNA topoisomerase inhibitors

PubMed Central

Kalra, Sean; Cleaver, Timothy G.; Merrick, Daniel; Wang, Xiao-Jing; Malkoski, Stephen P.

2015-01-01

Non-small cell lung cancer (NSCLC) is a common malignancy with a poor prognosis. Despite progress targeting oncogenic drivers, there are no therapies targeting tumor suppressor loss. Smad4 is an established tumor suppressor in pancreatic and colon cancer, however, the consequences of Smad4 loss in lung cancer are largely unknown. We evaluated Smad4 expression in human NSCLC samples and examined Smad4 alterations in large NSCLC datasets and found that reduced Smad4 expression is common in human NSCLC and occurs through a variety of mechanisms including mutation, homozygous deletion, and heterozygous loss. We modeled Smad4 loss in lung cancer by deleting Smad4 in airway epithelial cells and found that Smad4 deletion both initiates and promotes lung tumor development. Interestingly, both Smad4−/− mouse tumors and human NSCLC samples with reduced Smad4 expression demonstrated increased DNA damage while Smad4 knockdown in lung cancer cells reduced DNA repair and increased apoptosis after DNA damage. In addition, Smad4 deficient NSCLC cells demonstrated increased sensitivity to both chemotherapeutics that inhibit DNA topoisomerase and drugs that block double strand DNA break repair by non-homologous end joining. In sum, these studies establish Smad4 as a lung tumor suppressor and suggest that the defective DNA repair phenotype of Smad4 deficient tumors can be exploited by specific therapeutic strategies. PMID:25893305

Dopamine and serotonin signaling during two sensitive developmental periods differentially impact adult aggressive and affective behaviors in mice.

PubMed

Yu, Q; Teixeira, C M; Mahadevia, D; Huang, Y; Balsam, D; Mann, J J; Gingrich, J A; Ansorge, M S

2014-06-01

Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5-HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically conferred MAOA or 5-HTT hypoactivity is associated with altered aggression and increased anxiety/depression. Here we test the hypothesis that increased monoamine signaling during development causes these paradoxical aggressive and affective phenotypes. We find that pharmacologic MAOA blockade during early postnatal development (P2-P21) but not during peri-adolescence (P22-41) increases anxiety- and depression-like behavior in adult (>P90) mice, mimicking the effect of P2-21 5-HTT inhibition. Moreover, MAOA blockade during peri-adolescence, but not P2-21 or P182-201, increases adult aggressive behavior, and 5-HTT blockade from P22-P41 reduced adult aggression. Blockade of the dopamine transporter, but not the norepinephrine transporter, during P22-41 also increases adult aggressive behavior. Thus, P2-21 is a sensitive period during which 5-HT modulates adult anxiety/depression-like behavior, and P22-41 is a sensitive period during which DA and 5-HT bi-directionally modulate adult aggression. Permanently altered DAergic function as a consequence of increased P22-P41 monoamine signaling might underlie altered aggression. In support of this hypothesis, we find altered aggression correlating positively with locomotor response to amphetamine challenge in adulthood. Proving that altered DA function and aggression are causally linked, we demonstrate that optogenetic activation of VTA DAergic neurons increases aggression. It therefore appears that genetic and pharmacologic factors impacting dopamine and serotonin signaling during sensitive developmental periods can modulate adult monoaminergic function and thereby alter risk for aggressive and emotional dysfunction.

Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?

PubMed

Slamberová, Romana; Schutová, Barbora; Hrubá, Lenka; Pometlová, Marie

2011-10-10

Methamphetamine (MA) is one of the most frequently used illicit drugs worldwide and also one of the most common drugs abused by pregnant women. Repeated administration of psychostimulants induces behavioral sensitization in response to treatment of the same or related drugs in rodents. The effect of prenatal MA exposure on sensitivity to drugs in adulthood is not yet fully determined. Because our most recent studies demonstrated that prenatal MA (5mg/kg) exposure makes adult rats more sensitive to acute injection of the same drug, we were interested whether the increased sensitivity corresponds with the increased drug-seeking behavior. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the conditioned place preference (CPP). The following psychostimulant drugs were used as a challenge in adulthood: MA (5mg/kg), amphetamine (5mg/kg) and cocaine (10mg/kg). All psychostimulant drugs induced increased drug-seeking behavior in adult male rats. However, while MA and amphetamine-induced increase in drug-seeking behavior did not differ based on the prenatal drug exposure, prenatally MA-exposed rats displayed tolerance effect to cocaine in adulthood. In addition, prenatally MA-exposed rats had decreased weight gain after administration of MA or amphetamine, while the weight of prenatally MA-exposed rats stayed unchanged after cocaine administration. Defecation was increased by all the drugs (MA, amphetamine and cocaine), while only amphetamine increased the tail temperature. In conclusion, our results did not confirm our hypothesis that prenatal MA exposure increases drug-seeking behavior in adulthood in the CPP test. Copyright © 2011 Elsevier B.V. All rights reserved.

Development of Neural Sensitivity to Face Identity Correlates with Perceptual Discriminability

PubMed Central

Barnett, Michael A.; Hartley, Jake; Gomez, Jesse; Stigliani, Anthony; Grill-Spector, Kalanit

2016-01-01

Face perception is subserved by a series of face-selective regions in the human ventral stream, which undergo prolonged development from childhood to adulthood. However, it is unknown how neural development of these regions relates to the development of face-perception abilities. Here, we used functional magnetic resonance imaging (fMRI) to measure brain responses of ventral occipitotemporal regions in children (ages, 5–12 years) and adults (ages, 19–34 years) when they viewed faces that parametrically varied in dissimilarity. Since similar faces generate lower responses than dissimilar faces due to fMRI adaptation, this design objectively evaluates neural sensitivity to face identity across development. Additionally, a subset of subjects participated in a behavioral experiment to assess perceptual discriminability of face identity. Our data reveal three main findings: (1) neural sensitivity to face identity increases with age in face-selective but not object-selective regions; (2) the amplitude of responses to faces increases with age in both face-selective and object-selective regions; and (3) perceptual discriminability of face identity is correlated with the neural sensitivity to face identity of face-selective regions. In contrast, perceptual discriminability is not correlated with the amplitude of response in face-selective regions or of responses of object-selective regions. These data suggest that developmental increases in neural sensitivity to face identity in face-selective regions improve perceptual discriminability of faces. Our findings significantly advance the understanding of the neural mechanisms of development of face perception and open new avenues for using fMRI adaptation to study the neural development of high-level visual and cognitive functions more broadly. SIGNIFICANCE STATEMENT Face perception, which is critical for daily social interactions, develops from childhood to adulthood. However, it is unknown what developmental changes in the brain lead to improved performance. Using fMRI in children and adults, we find that from childhood to adulthood, neural sensitivity to changes in face identity increases in face-selective regions. Critically, subjects' perceptual discriminability among faces is linked to neural sensitivity: participants with higher neural sensitivity in face-selective regions demonstrate higher perceptual discriminability. Thus, our results suggest that developmental increases in face-selective regions' sensitivity to face identity improve perceptual discrimination of faces. These findings significantly advance understanding of the neural mechanisms underlying the development of face perception and have important implications for assessing both typical and atypical development. PMID:27798143

The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

PubMed Central

Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

2011-01-01

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI. PMID:21209786

The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

PubMed

Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

2010-12-26

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.

A sensitive and selective resonance Rayleigh scattering method for quick detection of avidin using affinity labeling Au nanoparticles

NASA Astrophysics Data System (ADS)

Wang, Qi; Huang, Xi; Fu, Xuan; Deng, Huan; Ma, Meihu; Cai, Zhaoxia

2016-06-01

Avidin is a glycoprotein with antinutritional property, which should be limited in daily food. We developed an affinity biosensor system based on resonance Rayleigh scattering (RRS) and using affinity biotin labeling Au nanoparticles (AuNPs). This method was selective and sensitive for quick avidin detection due to the avidin-biotin affinitive interaction. Under optimal conditions, RRS intensity of biotin-AuNPs increase linearly with an increasing concentration of avidin from 5 to 160 ng/mL. The lower limit of detection was 0.59 ng/mL. This rapid and selective avidin detection method was used in synthetic samples and egg products with recoveries of between 102.97 and 107.92%, thereby demonstrating the feasible and practical application of this assay.

Application of different enzyme assays and biomarkers for pollution monitoring of the marine environment.

PubMed

Seitkalieva, Alexandra V; Menzorova, Natalie I; Rasskazov, Valerу A

2016-01-01

New phosphatase and DNase inhibition tests for assessing the total pollution of a natural marine ecosystem were applied. The seawater samples with different pollution degrees were collected in the Troitsa Bay of the Peter the Great Bay (the Sea of Japan). The sensitivity of the alkaline phosphatase test to integrated pollution was in accordance with the sensitivity of the standard sea urchin sperm cell toxicity test. The increased seawater pollution level was shown to result in an up to fourfold increase in specific activities of acid and alkaline phosphatases from the mussel Crenomytilus grayanus. It was demonstrated that a complex methodological approach can be used to assess marine water areas, as well as to assess the biological conditions of invertebrates adapting to different environmental and anthropogenic effects.

Increase of dopamine D2(High) receptors in the striatum of rats sensitized to caffeine motor effects.

PubMed

Simola, Nicola; Morelli, Micaela; Seeman, Philip

2008-05-01

It has been previously demonstrated how rats can develop behavioral dopamine supersensitivity after long-term administration of caffeine. Since behavioral dopamine supersensitivity in rats is usually accompanied by an elevation in striatal dopamine D2(High) receptors, we examined whether alterations in D2(High) receptors occurred in the striatum of rats administered caffeine according to a regimen capable of eliciting behavioral dopamine supersensitivity (15 mg/kg i.p. every other day for 14 days). An increase of 126% in striatal D2(High) receptors was found in caffeine-sensitized rats. This marked elevation in D2(High) receptors may account for the caffeine-induced behavioral dopamine supersensitivity and may help elucidate the interactions between caffeine and dopamine neurotransmission. (c) 2008 Wiley-Liss, Inc.

The role of changes in the sensitivity of hepatic mitochondrial overt carnitine palmitoyltransferase in determining the onset of the ketosis of starvation in the rat.

PubMed Central

Drynan, L; Quant, P A; Zammit, V A

1996-01-01

The relationships between the increase in blood ketone-body concentrations and several parameters that can potentially influence the rate of hepatic fatty acid oxidation were studied during progressive starvation (up to 24 h) in the rat in order to discover whether the sensitivity of mitochondrial overt carnitine palmitoyltransferase (CPT I) to malonyl-CoA plays an important part in determining the intrahepatic potential for fatty acid oxidation during the onset of ketogenic conditions. A rapid increase in blood ketone-body concentration occurred between 12 and 16 h of starvation, several hours after the marked fall in hepatic malonyl-CoA and in serum insulin concentrations and doubling of plasma non-esterfied fatty acid (NEFA) concentration. Consequently, both the changes in hepatic malonyl-CoA and serum NEFA preceded the increase in blood ketone-body concentration by several hours. The maximal activity of CPT I increased gradually throughout the 24 h period of starvation, but the increases did not become significant before 18 h of starvation. By contrast, the sensitivity of CPT I to malonyl-CoA and the increase in blood ketone-body concentration followed an identical time course, demonstrating the central importance of this parameter in determining the ketogenic response of the liver to the onset of the starved state. PMID:8836117

Related-to-receptor tyrosine kinase receptor regulates hematopoietic stem and progenitor sensitivity to myelosuppressive injury in mice.

PubMed

Povinelli, Benjamin J; Srivastava, Pragya; Nemeth, Michael J

2015-03-01

Maintaining a careful balance between quiescence and proliferation of hematopoietic stem and progenitor cells (HSPCs) is necessary for lifelong blood formation. Previously, we demonstrated that the Wnt5a ligand inhibits HSPC proliferation through a functional interaction with a noncanonical Wnt ligand receptor termed 'related-to-receptor tyrosine kinase' (Ryk). Expression of Ryk on HSPCs in vivo is associated with a lower rate of proliferation, and, following treatment with fluorouracil (5-FU), the percentage of Ryk(+/high) HSPCs increased and the percentage of Ryk(-/low) HSPCs decreased. Based on these data, we hypothesized that one function of the Ryk receptor is to protect HSPCs from the effects of myeloablative agents. We found that Ryk expression on HSPCs is associated with lower rates of apoptosis following 5-FU and radiation. Transient inhibition of Ryk signaling in vivo resulted in increased hematopoietic-stem-cell proliferation and decreased hematopoietic-stem-cell function in bone marrow transplant assays. Furthermore, inhibition of Ryk signaling sensitized HSPCs to 5-FU treatment in association with increased levels of reactive oxygen species. Together, these results demonstrated an association between Ryk expression and survival of HSPCs following suppressive injury. Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Aging and episodic ozone exposure in Brown Norway rats: Effects on heart rate, core temperature, pulmonary function, and expression of serum biomarkers.

EPA Science Inventory

Ozone (03) is an air pollutant that is associated with cardiovascular and respiratory diseases. The aged population is considered to be more sensitive to pollutants such as 03;however, relatively few studies have demonstrated increased susceptibility in aged or senescent animal m...

The disposition index does not reflect β-cell function in IGT subjects treated with pioglitazone.

PubMed

DeFronzo, Ralph A; Tripathy, Devjit; Abdul-Ghani, Muhammad; Musi, Nicolas; Gastaldelli, Amalia

2014-10-01

The insulin secretion/insulin resistance (IR) (disposition) index (ΔI/ΔG ÷ IR, where Δ is change from baseline, I is insulin, and G is glucose) is commonly used as a measure of β-cell function. This relationship is curvilinear and becomes linear when log transformed. ΔI is determined by 2 variables: insulin secretion rate (ISR) and metabolic clearance of insulin. We postulated that the characteristic curvilinear relationship would be lost if Δ plasma C-peptide (ΔCP) (instead of Δ plasma insulin) was plotted against insulin sensitivity. A total of 441 individuals with impaired glucose tolerance (IGT) from ACT NOW received an oral glucose tolerance test and were randomized to pioglitazone or placebo for 2.4 years. Pioglitazone reduced IGT conversion to diabetes by 72% (P < .0001). ΔI/ΔG vs the Matsuda index of insulin sensitivity showed the characteristic curvilinear relationship. However, when ΔCP/ΔG or ΔISR/ΔG was plotted against the Matsuda index, the curvilinear relationship was completely lost. This discordance was explained by 2 distinct physiologic effects that altered plasma insulin response in opposite directions: 1) increased ISR and 2) augmented metabolic clearance of insulin. The net result was a decline in the plasma insulin response to hyperglycemia during the oral glucose tolerance test. These findings demonstrate a physiologic control mechanism wherein the increase in ISR ensures adequate insulin delivery into the portal circulation to suppress hepatic glucose production while delivering a reduced but sufficient amount of insulin to peripheral tissues to maintain the pioglitazone-mediated improvement in insulin sensitivity without excessive hyperinsulinemia. These results demonstrate the validity of the disposition index when relating the plasma insulin response to insulin sensitivity but underscore the pitfall of this index when drawing conclusions about β-cell function, because insulin secretion declined despite an increase in the plasma insulin response.

An Externally Dispersed Interferometer for Sensitive Doppler Extrasolar Planet Searches

NASA Astrophysics Data System (ADS)

Ge, Jian; Erskine, David J.; Rushford, Mike

2002-09-01

A new kind of instrument for sensitive Doppler extrasolar planet searches, called an externally dispersed interferometer, is described in this paper. It is a combination of an optical Michelson-type interferometer and an intermediate-resolution grating spectrometer. The interferometer measures Doppler radial velocity (RV) variations of starlight through the phase shifts of moiré fringes, created by multiplication of the interferometer fringes with stellar absorption lines. The intermediate-resolution spectrograph disperses the moiré fringes into thousands of parallel-wavelength channels. This increases the instrument bandwidth and fringe visibility by preventing fringe cross-talk between neighboring spectral lines. This results in a net increase in the signal-to-noise ratio over an interferometer used alone with broadband light. Compared to current echelle spectrometers for extrasolar planet searches, this instrument offers two unique instrument properties: a simple, stable, well-defined sinusoidal instrument response function (point-spread function) and magnification of Doppler motion through moiré fringe techniques. Since instrument noise is chiefly limited by the ability to characterize the instrument response, this new technique provides unprecedented low instrumental noise in an economical compact apparatus, enabling higher precision for Doppler RV measurements. In practice, the moiré magnification can be 5-10 times depending on the interferometer comb angle. This instrument has better sensitivity for smaller Doppler shifts than echelle spectrometers. The instrument can be designed with much lower spectral resolving power without losing Doppler sensitivity and optimized for higher throughput than echelle spectrometers to allow a potential survey for planets around fainter stars than current magnitude limits. Lab-based experiments with a prototype instrument with a spectral resolution of R~20,000 demonstrated ~0.7 m s-1 precision for short-term RV measurements. A fiber-fed version of the prototype with R~5600 was tested with starlight at the Lick 1 m telescope and demonstrated ~7 m s-1 RV precision at 340 Å bandwidth. The increased velocity noise is attributed to the lower spectral resolution, lower fringe visibility, and uncontrolled instrument environment.

A cooperative-binding split aptamer assay for rapid, specific and ultra-sensitive fluorescence detection of cocaine in saliva.

PubMed

Yu, Haixiang; Canoura, Juan; Guntupalli, Bhargav; Lou, Xinhui; Xiao, Yi

2017-01-01

Sensors employing split aptamers that reassemble in the presence of a target can achieve excellent specificity, but the accompanying reduction of target affinity mitigates any overall gains in sensitivity. We for the first time have developed a split aptamer that achieves enhanced target-binding affinity through cooperative binding. We have generated a split cocaine-binding aptamer that incorporates two binding domains, such that target binding at one domain greatly increases the affinity of the second domain. We experimentally demonstrate that the resulting cooperative-binding split aptamer (CBSA) exhibits higher target binding affinity and is far more responsive in terms of target-induced aptamer assembly compared to the single-domain parent split aptamer (PSA) from which it was derived. We further confirm that the target-binding affinity of our CBSA can be affected by the cooperativity of its binding domains and the intrinsic affinity of its PSA. To the best of our knowledge, CBSA-5335 has the highest cocaine affinity of any split aptamer described to date. The CBSA-based assay also demonstrates excellent performance in target detection in complex samples. Using this CBSA, we achieved specific, ultra-sensitive, one-step fluorescence detection of cocaine within fifteen minutes at concentrations as low as 50 nM in 10% saliva without signal amplification. This limit of detection meets the standards recommended by the European Union's Driving under the Influence of Drugs, Alcohol and Medicines program. Our assay also demonstrates excellent reproducibility of results, confirming that this CBSA-platform represents a robust and sensitive means for cocaine detection in actual clinical samples.

Significant performance enhancement in photoconductive terahertz optoelectronics by incorporating plasmonic contact electrodes.

PubMed

Berry, C W; Wang, N; Hashemi, M R; Unlu, M; Jarrahi, M

2013-01-01

Even though the terahertz spectrum is well suited for chemical identification, material characterization, biological sensing and medical imaging, practical development of these applications has been hindered by attributes of existing terahertz optoelectronics. Here we demonstrate that the use of plasmonic contact electrodes can significantly mitigate the low-quantum efficiency performance of photoconductive terahertz optoelectronics. The use of plasmonic contact electrodes offers nanoscale carrier transport path lengths for the majority of photocarriers, increasing the number of collected photocarriers in a subpicosecond timescale and, thus, enhancing the optical-to-terahertz conversion efficiency of photoconductive terahertz emitters and the detection sensitivity of photoconductive terahertz detectors. We experimentally demonstrate 50 times higher terahertz radiation powers from a plasmonic photoconductive emitter in comparison with a similar photoconductive emitter with non-plasmonic contact electrodes, as well as 30 times higher terahertz detection sensitivities from a plasmonic photoconductive detector in comparison with a similar photoconductive detector with non-plasmonic contact electrodes.

High Sensitivity Terahertz Detection through Large-Area Plasmonic Nano-Antenna Arrays.

PubMed

Yardimci, Nezih Tolga; Jarrahi, Mona

2017-02-16

Plasmonic photoconductive antennas have great promise for increasing responsivity and detection sensitivity of conventional photoconductive detectors in time-domain terahertz imaging and spectroscopy systems. However, operation bandwidth of previously demonstrated plasmonic photoconductive antennas has been limited by bandwidth constraints of their antennas and photoconductor parasitics. Here, we present a powerful technique for realizing broadband terahertz detectors through large-area plasmonic photoconductive nano-antenna arrays. A key novelty that makes the presented terahertz detector superior to the state-of-the art is a specific large-area device geometry that offers a strong interaction between the incident terahertz beam and optical pump at the nanoscale, while maintaining a broad operation bandwidth. The large device active area allows robust operation against optical and terahertz beam misalignments. We demonstrate broadband terahertz detection with signal-to-noise ratio levels as high as 107 dB.

High Sensitivity Terahertz Detection through Large-Area Plasmonic Nano-Antenna Arrays

PubMed Central

Yardimci, Nezih Tolga; Jarrahi, Mona

2017-01-01

Plasmonic photoconductive antennas have great promise for increasing responsivity and detection sensitivity of conventional photoconductive detectors in time-domain terahertz imaging and spectroscopy systems. However, operation bandwidth of previously demonstrated plasmonic photoconductive antennas has been limited by bandwidth constraints of their antennas and photoconductor parasitics. Here, we present a powerful technique for realizing broadband terahertz detectors through large-area plasmonic photoconductive nano-antenna arrays. A key novelty that makes the presented terahertz detector superior to the state-of-the art is a specific large-area device geometry that offers a strong interaction between the incident terahertz beam and optical pump at the nanoscale, while maintaining a broad operation bandwidth. The large device active area allows robust operation against optical and terahertz beam misalignments. We demonstrate broadband terahertz detection with signal-to-noise ratio levels as high as 107 dB. PMID:28205615

Employing Sensitivity Derivatives for Robust Optimization under Uncertainty in CFD

NASA Technical Reports Server (NTRS)

Newman, Perry A.; Putko, Michele M.; Taylor, Arthur C., III

2004-01-01

A robust optimization is demonstrated on a two-dimensional inviscid airfoil problem in subsonic flow. Given uncertainties in statistically independent, random, normally distributed flow parameters (input variables), an approximate first-order statistical moment method is employed to represent the Computational Fluid Dynamics (CFD) code outputs as expected values with variances. These output quantities are used to form the objective function and constraints. The constraints are cast in probabilistic terms; that is, the probability that a constraint is satisfied is greater than or equal to some desired target probability. Gradient-based robust optimization of this stochastic problem is accomplished through use of both first and second-order sensitivity derivatives. For each robust optimization, the effect of increasing both input standard deviations and target probability of constraint satisfaction are demonstrated. This method provides a means for incorporating uncertainty when considering small deviations from input mean values.

Examining the Latent Structure of Anxiety Sensitivity in Adolescents using Factor Mixture Modeling

PubMed Central

Allan, Nicholas P.; MacPherson, Laura; Young, Kevin C.; Lejuez, Carl W.; Schmidt, Norman B.

2014-01-01

Anxiety sensitivity has been implicated as an important risk factor, generalizable to most anxiety disorders. In adults, factor mixture modeling has been used to demonstrate that anxiety sensitivity is best conceptualized as categorical between individuals. That is, whereas most adults appear to possess normative levels of anxiety sensitivity, a small subset of the population appears to possess abnormally high levels of anxiety sensitivity. Further, those in the high anxiety sensitivity group are at increased risk of having high levels of anxiety and of having an anxiety disorder. This study was designed to determine whether these findings extend to adolescents. Factor mixture modeling was used to examine the best fitting model of anxiety sensitivity in a sample of 277 adolescents (M age = 11.0, SD = .81). Consistent with research in adults, the best fitting model consisted of two classes, one containing adolescents with high levels of anxiety sensitivity (n = 25), and another containing adolescents with normative levels of anxiety sensitivity (n = 252). Examination of anxiety sensitivity subscales revealed that the social concerns subscale was not important for classification of individuals. Convergent and discriminant validity of anxiety sensitivity classes were found in that membership in the high anxiety sensitivity class was associated with higher mean levels of anxiety symptoms, controlling for depression and externalizing problems, and was not associated with higher mean levels of depression or externalizing symptoms controlling for anxiety problems. PMID:24749756

Novel Connections Between DNA Replication, Telomere Homeostasis, and the DNA Damage Response Revealed by a Genome-Wide Screen for TEL1/ATM Interactions in Saccharomyces cerevisiae

PubMed Central

Piening, Brian D.; Huang, Dongqing; Paulovich, Amanda G.

2013-01-01

Tel1 is the budding yeast ortholog of the mammalian tumor suppressor and DNA damage response (DDR) kinase ATM. However, tel1-Δ cells, unlike ATM-deficient cells, do not exhibit sensitivity to DNA-damaging agents, but do display shortened (but stably maintained) telomere lengths. Neither the extent to which Tel1p functions in the DDR nor the mechanism by which Tel1 contributes to telomere metabolism is well understood. To address the first question, we present the results from a comprehensive genome-wide screen for genetic interactions with tel1-Δ that cause sensitivity to methyl methanesulfonate (MMS) and/or ionizing radiation, along with follow-up characterizations of the 13 interactions yielded by this screen. Surprisingly, many of the tel1-Δ interactions that confer DNA damage sensitivity also exacerbate the short telomere phenotype, suggesting a connection between these two phenomena. Restoration of normal telomere length in the tel1-Δ xxx-Δ mutants results in only minor suppression of the DNA damage sensitivity, demonstrating that the sensitivity of these mutants must also involve mechanisms independent of telomere length. In support of a model for increased replication stress in the tel1-Δ xxx-Δ mutants, we show that depletion of dNTP pools through pretreatment with hydroxyurea renders tel1-Δ cells (but not wild type) MMS-sensitive, demonstrating that, under certain conditions, Tel1p does indeed play a critical role in the DDR. PMID:23378069

Sensitivity and proportionality assessment of metabolites from microdose to high dose in rats using LC-MS/MS.

PubMed

Ni, Jinsong; Ouyang, Hui; Seto, Carmai; Sakuma, Takeo; Ellis, Robert; Rowe, Josh; Acheampong, Andrew; Welty, Devin; Szekely-Klepser, Gabriella

2010-03-01

The objective of this study was to evaluate the sensitivity requirement for LC-MS/MS as an analytical tool to characterize metabolites in plasma and urine at microdoses in rats and to investigate proportionality of metabolite exposure from a microdose of 1.67 µg/kg to a high dose of 5000 µg/kg for atorvastatin, ofloxacin, omeprazole and tamoxifen. Only the glucuronide metabolite of ofloxacin, the hydroxylation metabolite of omeprazole and the hydration metabolite of tamoxifen were characterized in rat plasma at microdose by LC-MS/MS. The exposure of detected metabolites of omeprazole and tamoxifen appeared to increase in a nonproportional manner with increasing doses. Exposure of ortho- and para-hydroxyatorvastatin, but not atorvastatin and lactone, increased proportionally with increasing doses. LC-MS/MS has demonstrated its usefulness for detecting and characterizing the major metabolites in plasma and urine at microdosing levels in rats. The exposure of metabolites at microdose could not simply be used to predict their exposure at higher doses.

Plasmonic crystal enhanced refractive index sensing

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

Stein, Benedikt; Devaux, Eloïse; Genet, Cyriaque, E-mail: genet@unistra.fr

2014-06-23

We demonstrate experimentally how the local anisotropy of the dispersion relation of surface plasmon modes propagating over periodic metal gratings can lead to an enhancement of the figure of merit of refractive index sensors. Exploiting the possibility to acquire defocused images of the Fourier space of a highly stable leakage radiation microscope, we report a twofold increase in sensing sensitivity close to the band gap of a one-dimensional plasmonic crystal where the anisotropy of the band structure is the most important. A practical sensing resolution of O(10{sup −6}) refractive index units is demonstrated.

Development of high-sensitivity SWIR APD receivers

NASA Astrophysics Data System (ADS)

Bai, Xiaogang; Yuan, Ping; Chang, James; Sudharsanan, Rengarajan; Krainak, Michael; Yang, Guangning; Sun, Xiaoli; Lu, Wei

2013-06-01

Emerging short wavelength infrared (SWIR) LIght Detection And Ranging (LIDAR) and long range laser rangefinder systems, require large optical aperture avalanche photodiodes (APDs) receivers with high sensitivity and high bandwidth. A large optical aperture is critical to increase the optical coupling efficiency and extend the LIDAR sensing range of the above systems. Both APD excess noise and transimpedance amplifier (TIA) noise need to be reduced in order to achieve high receiver sensitivity. The dark current and capacitance of large area APDs increase with APD aperture and thus limit the sensitivity and bandwidth of receivers. Spectrolab has been developing low excess noise InAlAs/InGaAs APDs with impact ionization engineering (I2E) designs for many years and has demonstrated APDs with optical gain over 100 utilizing multiple period I2E structures in the APD multiplier. These high gain I2E APDs have an excess noise factor less than 0.15. With an optical aperture of 200 μm, low excess noise multiple periods I2E APDs have capacitances about 1.7 pF. In addition, optical gains of InAlAs based APDs show very little temperature dependence and will enable APD photoreceivers without thermal electric cooling.

[Silencing MSH3 expression enhances cisplatin sensitivity of human tongue cancer cells].

PubMed

Fan, Xiao-Sheng; Cao, Fang-Yun; Li, Kuang-Zheng

2016-08-20

To explore the effect of MSH3 knock-down on sensitivity of tongue cancer cells to cisplatin. Three small interfering RNA (siRNA) fragments targeting MSH3 CDS region were synthesized and transfected into CAL27 cells via Lipofectamine. Real-time PCR and Western blotting were used to assess the efficiency of MSH3 silencing. MTS, apoptosis staining and cell immunofluorescence assay were used to examine the cisplatin sensitivity, apoptosis and DNA repair of transfected CAL27 cells. s One of the 3 siRNAs was found to significantly reduce the expression of MSH3 protein in CAL27 cells (P<0.05). MTS assay showed that MSH3 silencing resulted in an significant reduction of IC50 of cisplatin from 21.32 to 13.95 µmol/L (P<0.05) and increased the apoptotic index of the exposed cells from 4.23∓1.27 to 11.32∓1.82 (P<0.05). Immunofluorescence assay demonstrated that silencing MSH3 markedly reduced the number of γ-H2AX foci. Silencing MSH3 can significantly increase cisplatin sensitivity of tongue cancer cells, the mechanism of which involves mainly attenuation of repair of DNA double-strand damage in the cells.

Proteasome phosphorylation regulates cocaine-induced sensitization.

PubMed

Gonzales, Frankie R; Howell, Kristin K; Dozier, Lara E; Anagnostaras, Stephan G; Patrick, Gentry N

2018-04-01

Repeated exposure to cocaine produces structural and functional modifications at synapses from neurons in several brain regions including the nucleus accumbens. These changes are thought to underlie cocaine-induced sensitization. The ubiquitin proteasome system plays a crucial role in the remodeling of synapses and has recently been implicated in addiction-related behavior. The ATPase Rpt6 subunit of the 26S proteasome is phosphorylated by Ca 2+ /calmodulin-dependent protein kinases II alpha at ser120 which is thought to regulate proteasome activity and distribution in neurons. Here, we demonstrate that Rpt6 phosphorylation is involved in cocaine-induced locomotor sensitization. Cocaine concomitantly increases proteasome activity and Rpt6 S120 phosphorylation in cultured neurons and in various brain regions of wild type mice including the nucleus accumbens and prefrontal cortex. In contrast, cocaine does not increase proteasome activity in Rpt6 phospho-mimetic (ser120Asp) mice. Strikingly, we found a complete absence of cocaine-induced locomotor sensitization in the Rpt6 ser120Asp mice. Together, these findings suggest a critical role for Rpt6 phosphorylation and proteasome function in the regulation cocaine-induced behavioral plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.

Highly sensitive torsion sensor based on long period fiber grating fabricated by femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Dong, Xinran; Xie, Zheng; Song, Yuxin; Yin, Kai; Luo, Zhi; Duan, Ji'an; Wang, Cong

2017-12-01

A highly sensitive torsion sensor based on long period fiber grating (LPFG) fabricated by 800 nm femtosecond laser pulses is proposed and demonstrated. LPFG with an attenuation depth of ∼14 dB is achieved within the wavelength range of 1425-1575 nm. The experiment results show that the LP02 and LP03 resonant wavelengths experience red-shift when the twist direction is clockwise while they occur blue-shift in the twist counterclockwise direction as the twist rate increases. However, the LP04 resonant wavelength is always shifted toward shorter wavelength independently of the twist directions and higher twist sensitivity is observed. In addition, the loss peak amplitude of LPFG shows a tendency to decrease with the twist rate increases whether the LPFG is twisted clockwise or counterclockwise. Meanwhile, the resonant wavelength occurs splitting phenomenon in the case of higher twist rate as well as the high order resonant wavelength performs more significantly. Additionally, the sensor shows a twist sensitivity as high as 118.7 pm/(rad/m) in the range of -105 to -52.5 rad/m and that of 181.7 pm/(rad/m) in the range of 52.5-105 rad/m.

Radiosensitization: enhancing the radiation inactivation of foodborne bacteria

NASA Astrophysics Data System (ADS)

Borsa, J.; Lacroix, M.; Ouattara, B.; Chiasson, F.

2004-09-01

Irradiation of meat products to kill pathogens can be limited by radiation-induced detriment of sensory quality. Since such detriment is directly related to dose, one approach to reduce it is by devising means to lower the dose of radiation required for processing. Increasing the radiation sensitivity of the target microorganisms would lower the dose required for a given level of microbial kill. In this work, the radiation sensitivities of inoculated Escherichia coli and Salmonella typhi in ground beef were examined under a variety of conditions. Results showed that specific manipulations of treatment conditions significantly increased the radiation sensitivity of the test organisms, ranging from a few percent to several-fold reduction in D10. In particular, radiation sensitization could be effected by certain additives, including carvacrol, thymol and trans-cinnamaldehyde, and also by certain compositions of modified atmosphere in the package headspace. A combination of additives and modified atmosphere effected a greater radiosensitization effect than could be achieved by either factor applied alone. Radiosensitization could be demonstrated with irradiation of either fresh or frozen ground meat. The radiosensitization phenomenon may be of practical utility in enhancing the technical effectiveness and feasibility of irradiation of a variety of meat and other food products.

Hormetic effect of methylmercury on Caenorhabditis elegans

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

Helmcke, Kirsten J., E-mail: Kirsten.J.Helmcke@gmail.com; Aschner, Michael, E-mail: Michael.Aschner@vanderbilt.ed

2010-10-15

Research has demonstrated the toxic effects of methylmercury (MeHg), yet molecular mechanisms underlying its toxicity are not completely understood. Caenorhabditis elegans (C. elegans) offers a unique biological model to explore mechanisms of MeHg toxicity given many advantages associated with its ease of use and genetic power. Since our previous work indicated neurotoxic resistance of C. elegans to MeHg, the present study was designed to examine molecular mechanisms associated with this resistance. We hypothesized MeHg would induce expression of gst, hsp or mtl in vivo since glutathione (GSH), heat shock proteins (HSPs), and metallothioneins (MTs) have shown involvement in MeHg toxicity.more » Our studies demonstrated a modest, but significant increase in fluorescence in gst-4::GFP and mtl-1::GFP strains at an acute, low L1 MeHg exposure, whereas chronic L4 MeHg exposure induced expression of gst-4::GFP and hsp-4::GFP. Knockout gst-4 animals showed no alterations in lethality sensitivity compared to wildtype animals whereas mtl knockouts displayed increased sensitivity to MeHg exposure. GSH levels were increased by acute MeHg treatment and depleted with chronic exposure. We also demonstrate that MeHg induces hormesis, a phenotype whereby a sublethal exposure to MeHg rendered C. elegans resistant to subsequent exposure to the organometal. The involvement of gst-4, hsp-4, mtl-1, and mtl-2 in hormesis was examined. An increase in gst-4::GFP expression after a low-dose acute exposure to MeHg indicated that gst-4 may be involved in this response. Our results implicate GSH, HSPs, and MTs in protecting C. elegans from MeHg toxicity and show a potential role of gst-4 in MeHg-induced hormesis.« less

ATHENA: A knowledge-based hybrid backpropagation-grammatical evolution neural network algorithm for discovering epistasis among quantitative trait Loci

PubMed Central

2010-01-01

Background Growing interest and burgeoning technology for discovering genetic mechanisms that influence disease processes have ushered in a flood of genetic association studies over the last decade, yet little heritability in highly studied complex traits has been explained by genetic variation. Non-additive gene-gene interactions, which are not often explored, are thought to be one source of this "missing" heritability. Methods Stochastic methods employing evolutionary algorithms have demonstrated promise in being able to detect and model gene-gene and gene-environment interactions that influence human traits. Here we demonstrate modifications to a neural network algorithm in ATHENA (the Analysis Tool for Heritable and Environmental Network Associations) resulting in clear performance improvements for discovering gene-gene interactions that influence human traits. We employed an alternative tree-based crossover, backpropagation for locally fitting neural network weights, and incorporation of domain knowledge obtainable from publicly accessible biological databases for initializing the search for gene-gene interactions. We tested these modifications in silico using simulated datasets. Results We show that the alternative tree-based crossover modification resulted in a modest increase in the sensitivity of the ATHENA algorithm for discovering gene-gene interactions. The performance increase was highly statistically significant when backpropagation was used to locally fit NN weights. We also demonstrate that using domain knowledge to initialize the search for gene-gene interactions results in a large performance increase, especially when the search space is larger than the search coverage. Conclusions We show that a hybrid optimization procedure, alternative crossover strategies, and incorporation of domain knowledge from publicly available biological databases can result in marked increases in sensitivity and performance of the ATHENA algorithm for detecting and modelling gene-gene interactions that influence a complex human trait. PMID:20875103

Comparison of Self-Reported Telephone Interviewing and Web-Based Survey Responses: Findings From the Second Australian Young and Well National Survey

PubMed Central

Davenport, Tracey A; Burns, Jane M; Hickie, Ian B

2017-01-01

Background Web-based self-report surveying has increased in popularity, as it can rapidly yield large samples at a low cost. Despite this increase in popularity, in the area of youth mental health, there is a distinct lack of research comparing the results of Web-based self-report surveys with the more traditional and widely accepted computer-assisted telephone interviewing (CATI). Objective The Second Australian Young and Well National Survey 2014 sought to compare differences in respondent response patterns using matched items on CATI versus a Web-based self-report survey. The aim of this study was to examine whether responses varied as a result of item sensitivity, that is, the item’s susceptibility to exaggeration on underreporting and to assess whether certain subgroups demonstrated this effect to a greater extent. Methods A subsample of young people aged 16 to 25 years (N=101), recruited through the Second Australian Young and Well National Survey 2014, completed the identical items on two occasions: via CATI and via Web-based self-report survey. Respondents also rated perceived item sensitivity. Results When comparing CATI with the Web-based self-report survey, a Wilcoxon signed-rank analysis showed that respondents answered 14 of the 42 matched items in a significantly different way. Significant variation in responses (CATI vs Web-based) was more frequent if the item was also rated by the respondents as highly sensitive in nature. Specifically, 63% (5/8) of the high sensitivity items, 43% (3/7) of the neutral sensitivity items, and 0% (0/4) of the low sensitivity items were answered in a significantly different manner by respondents when comparing their matched CATI and Web-based question responses. The items that were perceived as highly sensitive by respondents and demonstrated response variability included the following: sexting activities, body image concerns, experience of diagnosis, and suicidal ideation. For high sensitivity items, a regression analysis showed respondents who were male (beta=−.19, P=.048) or who were not in employment, education, or training (NEET; beta=−.32, P=.001) were significantly more likely to provide different responses on matched items when responding in the CATI as compared with the Web-based self-report survey. The Web-based self-report survey, however, demonstrated some evidence of avidity and attrition bias. Conclusions Compared with CATI, Web-based self-report surveys are highly cost-effective and had higher rates of self-disclosure on sensitive items, particularly for respondents who identify as male and NEET. A drawback to Web-based surveying methodologies, however, includes the limited control over avidity bias and the greater incidence of attrition bias. These findings have important implications for further development of survey methods in the area of health and well-being, especially when considering research topics (in this case diagnosis, suicidal ideation, sexting, and body image) and groups that are being recruited (young people, males, and NEET). PMID:28951382

Zooming in on vibronic structure by lowest-value projection reconstructed 4D coherent spectroscopy

NASA Astrophysics Data System (ADS)

Harel, Elad

2018-05-01

A fundamental goal of chemical physics is an understanding of microscopic interactions in liquids at and away from equilibrium. In principle, this microscopic information is accessible by high-order and high-dimensionality nonlinear optical measurements. Unfortunately, the time required to execute such experiments increases exponentially with the dimensionality, while the signal decreases exponentially with the order of the nonlinearity. Recently, we demonstrated a non-uniform acquisition method based on radial sampling of the time-domain signal [W. O. Hutson et al., J. Phys. Chem. Lett. 9, 1034 (2018)]. The four-dimensional spectrum was then reconstructed by filtered back-projection using an inverse Radon transform. Here, we demonstrate an alternative reconstruction method based on the statistical analysis of different back-projected spectra which results in a dramatic increase in sensitivity and at least a 100-fold increase in dynamic range compared to conventional uniform sampling and Fourier reconstruction. These results demonstrate that alternative sampling and reconstruction methods enable applications of increasingly high-order and high-dimensionality methods toward deeper insights into the vibronic structure of liquids.

PCB 136 Atropselectively Alters Morphometric and Functional Parameters of Neuronal Connectivity in Cultured Rat Hippocampal Neurons via Ryanodine Receptor-Dependent Mechanisms

PubMed Central

Yang, Dongren; Kania-Korwel, Izabela; Ghogha, Atefeh; Chen, Hao; Stamou, Marianna; Bose, Diptiman D.; Pessah, Isaac N.; Lehmler, Hans-Joachim; Lein, Pamela J.

2014-01-01

We recently demonstrated that polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyRs), and this activity promotes Ca2+-dependent dendritic growth in cultured neurons. Many ortho-substituted congeners display axial chirality, and we previously reported that the chiral congener PCB 136 (2,2′,3,3′,6,6′-hexachlorobiphenyl) atropselectively sensitizes RyRs. Here, we test the hypothesis that PCB 136 atropisomers differentially alter dendritic growth and other parameters of neuronal connectivity influenced by RyR activity. (−)-PCB 136, which potently sensitizes RyRs, enhances dendritic growth in primary cultures of rat hippocampal neurons, whereas (+)-PCB 136, which lacks RyR activity, has no effect on dendritic growth. The dendrite-promoting activity of (−)-PCB 136 is observed at concentrations ranging from 0.1 to 100nM and is blocked by pharmacologic RyR antagonism. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB 136 atropisomers in hippocampal cultures indicates that atropselective effects on dendritic growth are not due to differential partitioning of atropisomers into cultured cells. Imaging of hippocampal neurons loaded with Ca2+-sensitive dye demonstrates that (−)-PCB 136 but not (+)-PCB 136 increases the frequency of spontaneous Ca2+ oscillations. Similarly, (−)-PCB 136 but not (+)-PCB 136 increases the activity of hippocampal neurons plated on microelectrode arrays. These data support the hypothesis that atropselective effects on RyR activity translate into atropselective effects of PCB 136 atropisomers on neuronal connectivity, and suggest that the variable atropisomeric enrichment of chiral PCBs observed in the human population may be a significant determinant of individual susceptibility for adverse neurodevelopmental outcomes following PCB exposure. PMID:24385416

Arm Dominance Affects Feedforward Strategy more than Feedback Sensitivity during a Postural Task

PubMed Central

Walker, Elise H. E.; Perreault, Eric J.

2015-01-01

Handedness is a feature of human motor control that is still not fully understood. Recent work has demonstrated that the dominant and nondominant arm each excel at different behaviors, and has proposed that this behavioral asymmetry arises from lateralization in the cerebral cortex: the dominant side specializes in predictive trajectory control, while the nondominant side is specialized for impedance control. Long-latency stretch reflexes are an automatic mechanism for regulating posture, and have been shown to contribute to limb impedance. To determine whether long-latency reflexes also contribute to asymmetric motor behavior in the upper limbs, we investigated the effect of arm dominance on stretch reflexes during a postural task that required varying degrees of impedance control. Our results demonstrated slightly but significantly larger reflex responses in the biarticular muscles of the nondominant arm, as would be consistent with increased impedance control. These differences were attributed solely to higher levels of voluntary background activity in the nondominant biarticular muscles, indicating that feedforward strategies for postural stability may differ between arms. Reflex sensitivity, which was defined as the magnitude of the reflex response for matched levels of background activity, was not significantly different between arms for a broad subject population ranging from 23–51 years of age. These results indicate that inter-arm differences in feedforward strategies are more influential during posture than differences in feedback sensitivity, in a broad subject population. Interestingly, restricting our analysis to subjects under 40 years of age revealed a small increase in long-latency reflex sensitivity in the nondominant arm relative to the dominant arm. Though our subject numbers were small for this secondary analysis, it suggests that further studies may be required to assess the influence of reflex lateralization throughout development. PMID:25850407

Thioredoxin reductase regulates AP-1 activity as well as thioredoxin nuclear localization via active cysteines in response to ionizing radiation.

PubMed

Karimpour, Shervin; Lou, Junyang; Lin, Lilie L; Rene, Luis M; Lagunas, Lucio; Ma, Xinrong; Karra, Sreenivasu; Bradbury, C Matthew; Markovina, Stephanie; Goswami, Prabhat C; Spitz, Douglas R; Hirota, Kiichi; Kalvakolanu, Dhananjaya V; Yodoi, Junji; Gius, David

2002-09-12

A recently identified class of signaling factors uses critical cysteine motif(s) that act as redox-sensitive 'sulfhydryl switches' to reversibly modulate specific signal transduction cascades regulating downstream proteins with similar redox-sensitive sites. For example, signaling factors such as redox factor-1 (Ref-1) and transcription factors such as the AP-1 complex both contain redox-sensitive cysteine motifs that regulate activity in response to oxidative stress. The mammalian thioredoxin reductase-1 (TR) is an oxidoreductase selenocysteine-containing flavoprotein that also appears to regulate multiple downstream intracellular redox-sensitive proteins. Since ionizing radiation (IR) induces oxidative stress as well as increases AP-1 DNA-binding activity via the activation of Ref-1, the potential roles of TR and thioredoxin (TRX) in the regulation of AP-1 activity in response to IR were investigated. Permanently transfected cell lines that overexpress wild type TR demonstrated constitutive increases in AP-1 DNA-binding activity as well as AP-1-dependent reporter gene expression, relative to vector control cells. In contrast, permanently transfected cell lines expressing a TR gene with the active site cysteine motif deleted were unable to induce AP-1 activity or reporter gene expression in response to IR. Transient genetic overexpression of either the TR wild type or dominant-negative genes demonstrated similar results using a transient assay system. One mechanism through which TR regulates AP-1 activity appears to involve TRX sub-cellular localization, with no change in the total TRX content of the cell. These results identify a novel function of the TR enzyme as a signaling factor in the regulation of AP-1 activity via a cysteine motif located in the protein.

Arm dominance affects feedforward strategy more than feedback sensitivity during a postural task.

PubMed

Walker, Elise H E; Perreault, Eric J

2015-07-01

Handedness is a feature of human motor control that is still not fully understood. Recent work has demonstrated that the dominant and nondominant arm each excel at different behaviors and has proposed that this behavioral asymmetry arises from lateralization in the cerebral cortex: the dominant side specializes in predictive trajectory control, while the nondominant side is specialized for impedance control. Long-latency stretch reflexes are an automatic mechanism for regulating posture and have been shown to contribute to limb impedance. To determine whether long-latency reflexes also contribute to asymmetric motor behavior in the upper limbs, we investigated the effect of arm dominance on stretch reflexes during a postural task that required varying degrees of impedance control. Our results demonstrated slightly but significantly larger reflex responses in the biarticular muscles of the nondominant arm, as would be consistent with increased impedance control. These differences were attributed solely to higher levels of voluntary background activity in the nondominant biarticular muscles, indicating that feedforward strategies for postural stability may differ between arms. Reflex sensitivity, which was defined as the magnitude of the reflex response for matched levels of background activity, was not significantly different between arms for a broad subject population ranging from 23 to 51 years of age. These results indicate that inter-arm differences in feedforward strategies are more influential during posture than differences in feedback sensitivity, in a broad subject population. Interestingly, restricting our analysis to subjects under 40 years of age revealed a small increase in long-latency reflex sensitivity in the nondominant arm relative to the dominant arm. Though our subject numbers were small for this secondary analysis, it suggests that further studies may be required to assess the influence of reflex lateralization throughout development.

The γ-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens.

PubMed

Fu, Zhenyu; Yang, Hongfa; Xiao, Yuqiang; Zhao, Gang; Huang, Haiyan

2012-07-10

Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA) system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear. We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo. The present study demonstrated that morphine challenge (3 mg/kg, s.c.) obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg) significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge. Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse.

Fear improves mental rotation of low-spatial-frequency visual representation.

PubMed

Borst, Grégoire

2013-10-01

Previous studies have demonstrated that the brief presentation of a fearful face improves not only low-level visual processing such as contrast and orientation sensitivity but also improves visuospatial processing. In the present study, we investigated whether fear improves mental rotation efficiency (i.e., the mental rotation rate) because of the effect of fear on the sensitivity of magnocellular neurons. We asked 2 groups of participants to perform a mental rotation task with either low-pass or high-pass filtered 3-dimensional objects. Following the presentation of a fearful face, participants mentally rotated objects faster compared with when a neutral face was presented but only for low-pass filtered objects. The results suggest that fear improves mental rotation efficiency by increasing sensitivity to motion-related visual information within the magnocellular pathway.

The fit and implementation of sexual harassment law to workplace evaluations.

PubMed

Wiener, Richard L; Hackney, Amy; Kadela, Karen; Rauch, Shannon; Seib, Hope; Warren, Laura; Hurt, Linda E

2002-08-01

Three studies used videotaped harassment complaints to examine the impact of legal standards on the evaluation of social-sexual conduct at work. Study 1 demonstrated that without legal instructions, college students' judgment strategies were highly variable. Study 2 compared 2 current legal standards, the "severity or pervasiveness test" and a proposed utilitarian alternative (i.e., the rational woman approach). Undergraduate participants taking the perspective of the complainant were more sensitive to offensive conduct than were those adopting an objective perspective. Although the utilitarian altemative further increased sensitivity on some measures, it failed to produce a principled judgment strategy. Finally, Study 3 examined the kinds of errors that full-time workers make when applying the "severity or pervasiveness" test to examine more closely the sensitivity of the subjective approach.

Radiosensitization of cancer cells by hydroxychalcones.

PubMed

Pruitt, Rory; Sasi, Nidhish; Freeman, Michael L; Sekhar, Konjeti R

2010-10-15

Radiation sensitization is significantly increased by proteotoxic stress, such as a heat shock. We undertook an investigation, seeking to identify natural products that induced proteotoxic stress and then determined if a compound exhibited radiosensitizing properties. The hydroxychalcones, 2',5'-dihydroxychalcone (D-601) and 2,2'-dihydroxychalcone (D-501), were found to activate heat shock factor 1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic cancer cells. The radiosensitization ability of D-601 was blocked by pretreatment with α-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A2 (CYP1A2), suggesting that the metabolite of D-601 is essential for radiosensitization. The study demonstrated the ability of hydroxychalcones to radiosensitize cancer cells and provides new leads for developing novel radiation sensitizers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Radiosensitization of Cancer Cells by Hydroxychalcones

PubMed Central

Pruitt, Rory; Sasi, Nidhish; Freeman, Michael L.; Sekhar, Konjeti R.

2010-01-01

Radiation sensitization is significantly increased by proteotoxic stress, such as a heat shock. We undertook an investigation, seeking to identify natural products that induced proteotoxic stress and then determined if a compound exhibited radiosensitizing properties. The hydroxychalcones, 2′,5′-dihydroxychalcone (D-601) and 2,2′-dihydroxychalcone (D-501), were found to activate heat shock factor 1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic cancer cells. The radiosensitization ability of D-601 was blocked by pretreatment with α-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A2 (CYP1A2), suggesting that the metabolite of D-601 is essential for radiosensitization. The study demonstrated the ability of hydroxychalcones to radiosensitize cancer cells and provides new leads for developing novel radiation sensitizers. PMID:20826087

Use of a sensitive EnVision +-based detection system for Western blotting: avoidance of streptavidin binding to endogenous biotin and biotin-containing proteins in kidney and other tissues.

PubMed

Banks, Rosamonde E; Craven, Rachel A; Harnden, Patricia A; Selby, Peter J

2003-04-01

Western blotting remains a central technique in confirming identities of proteins, their quantitation and analysis of various isoforms. The biotin-avidin/streptavidin system is often used as an amplification step to increase sensitivity but in some tissues such as kidney, "nonspecific" interactions may be a problem due to high levels of endogenous biotin-containing proteins. The EnVision system, developed for immunohistochemical applications, relies on binding of a polymeric conjugate consisting of up to 100 peroxidase molecules and 20 secondary antibody molecules linked directly to an activated dextran backbone, to the primary antibody. This study demonstrates that it is also a viable and sensitive alternative detection system in Western blotting applications.

Nano-machining of biosensor electrodes through gold nanoparticles deposition produced by femtosecond laser ablation

NASA Astrophysics Data System (ADS)

Della Ventura, B.; Funari, R.; Anoop, K. K.; Amoruso, S.; Ausanio, G.; Gesuele, F.; Velotta, R.; Altucci, C.

2015-06-01

We report an application of femtosecond laser ablation to improve the sensitivity of biosensors based on a quartz crystal microbalance device. The nanoparticles produced by irradiating a gold target with 527-nm, 300-fs laser pulses, in high vacuum, are directly deposited on the quartz crystal microbalance electrode. Different gold electrodes are fabricated by varying the deposition time, thus addressing how the nanoparticles surface coverage influences the sensor response. The modified biosensor is tested by weighting immobilized IgG antibody from goat and its analyte (IgG from mouse), and the results are compared with a standard electrode. A substantial increase of biosensor sensitivity is achieved, thus demonstrating that femtosecond laser ablation and deposition is a viable physical method to improve the biosensor sensitivity by means of nanostructured electrodes.

Viability, biofilm formation, and MazEF expression in drug-sensitive and drug-resistant Mycobacterium tuberculosis strains circulating in Xinjiang, China.

PubMed

Zhao, Ji-Li; Liu, Wei; Xie, Wan-Ying; Cao, Xu-Dong; Yuan, Li

2018-01-01

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is one of the most common chronic infectious amphixenotic diseases worldwide. Prevention and control of TB are greatly difficult, due to the increase in drug-resistant TB, particularly multidrug-resistant TB. We speculated that there were some differences between drug-sensitive and drug-resistant MTB strains and that mazEF 3,6,9 toxin-antitoxin systems (TASs) were involved in MTB viability. This study aimed to investigate differences in viability, biofilm formation, and MazEF expression between drug-sensitive and drug-resistant MTB strains circulating in Xinjiang, China, and whether mazEF 3,6,9 TASs contribute to MTB viability under stress conditions. Growth profiles and biofilm-formation abilities of drug-sensitive, drug-resistant MTB strains and the control strain H37Rv were monitored. Using molecular biology experiments, the mRNA expression of the mazF 3, 6, and 9 toxin genes, the mazE 3, 6, and 9 antitoxin genes, and expression of the MazF9 protein were detected in the different MTB strains, H37RvΔ mazEF 3,6,9 mutants from the H37Rv parent strain were generated, and mutant viability was tested. Ex vivo culture analyses demonstrated that drug-resistant MTB strains exhibit higher survival rates than drug-sensitive strains and the control strain H37Rv. However, there was no statistical difference in biofilm-formation ability in the drug-sensitive, drug-resistant, and H37Rv strains. mazE 3,6 mRNA-expression levels were relatively reduced in the drug-sensitive and drug-resistant strains compared to H37Rv. Conversely, mazE 3,9 expression was increased in drug-sensitive strains compared to drug-resistant strains. Furthermore, compared with the H37Rv strain, mazF 3,6 expression was increased in drug-resistant strains, mazF 9 expression was increased in drug-sensitive strains, and mazF 9 exhibited reduced expression in drug-resistant strains compared with drug-sensitive strains. Protein expression of mazF9 was increased in drug-sensitive and drug-resistant strains compared to H37Rv, while drug-resistant strains exhibited reduced mazF9 expression compared to drug-sensitive strains. Compared to H37Rv, H37RvΔ mazEF 3,6,9-deletion mutants grew more slowly under both stress conditions, and their ability to survive in host macrophages was also weaker. Furthermore, the host macrophage-apoptosis rate was higher after infection with any of the H37RvΔ mazE F3,6,9 mutants than with the H37Rv strain. The increased viability of MTB drug-resistant strains compared with drug-sensitive strains is likely to be related to differential MazEF mRNA and protein expression. mazEF 3,6,9 TASs contribute to MTB viability under stress conditions.

Au/NiFe/M(Au, MoS2, graphene) trilayer magnetoplasmonics DNA-hybridized sensors with high record of sensitivity.

PubMed

Faridi, Ehsan; Moradi, Maryam; Ansari, Narges; Baradaran Ghasemi, Amir Hossein; Afshar, Amir; Mohseni Armaki, Seyed Majid

2017-12-01

The demonstration of biosensors based on the surface plasmon effect holds promise for future high-sensitive electrodeless biodetection. The combination of magnetic effects with surface plasmon waves brings additional freedom to improve sensitivity and signal selectivity. Stacking biosensors with two-dimensional (2-D) materials, e.g., graphene (Gr) and MoS2, can influence plasmon waves and facilitate surface physiochemical properties as additional versatility aspects. We demonstrate magnetoplasmonic biosensors through the detuning of surface plasmon oscillation modes affected by magnetic effect via the presence of the NiFe (Py) layer and different light absorbers of Gr, MoS2, and Au ultrathin layers in three stacks of Au/Py/M(MoS2, Gr, Au) trilayers. We found minimum reflection, resonance angle shift, and transverse magneto-optical Kerr effect (TMOKE) responses of all sensors in the presence of the ss-DNA monolayer. Very few changes of ∼5×10-7 in the ss-DNA's refractive index result in valuable TMOKE response. We found that the presence of three-layer Gr and two-layer MoS2 on top of the Au/Py bilayer can dramatically increase the sensitivity by nine and four times, respectively, than the conventional Au/Co/Au trilayer. Our results show the highest reported DNA sensitivity based on the coupling of light with 2-D materials in magnetoplasmonic devices. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Oligomerization of Clostridium perfringens Epsilon Toxin Is Dependent upon Caveolins 1 and 2

PubMed Central

Fennessey, Christine M.; Sheng, Jinsong; Rubin, Donald H.; McClain, Mark S.

2012-01-01

Evidence from multiple studies suggests that Clostridium perfringens ε-toxin is a pore-forming toxin, assembling into oligomeric complexes in the plasma membrane of sensitive cells. In a previous study, we used gene-trap mutagenesis to identify mammalian factors contributing to toxin activity, including caveolin-2 (CAV2). In this study, we demonstrate the importance of caveolin-2 and its interaction partner, caveolin-1 (CAV1), in ε-toxin-induced cytotoxicity. Using CAV2-specific shRNA in a toxin-sensitive human kidney cell line, ACHN, we confirmed that cells deficient in CAV2 exhibit increased resistance to ε-toxin. Similarly, using CAV1-specific shRNA, we demonstrate that cells deficient in CAV1 also exhibit increased resistance to the toxin. Immunoprecipitation of CAV1 and CAV2 from ε-toxin-treated ACHN cells demonstrated interaction of both CAV1 and -2 with the toxin. Furthermore, blue-native PAGE indicated that the toxin and caveolins were components of a 670 kDa protein complex. Although ε-toxin binding was only slightly perturbed in caveolin-deficient cells, oligomerization of the toxin was dramatically reduced in both CAV1- and CAV2-deficient cells. These results indicate that CAV1 and -2 potentiate ε-toxin induced cytotoxicity by promoting toxin oligomerization – an event which is requisite for pore formation and, by extension, cell death. PMID:23056496

Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2.

PubMed

Fennessey, Christine M; Sheng, Jinsong; Rubin, Donald H; McClain, Mark S

2012-01-01

Evidence from multiple studies suggests that Clostridium perfringens ε-toxin is a pore-forming toxin, assembling into oligomeric complexes in the plasma membrane of sensitive cells. In a previous study, we used gene-trap mutagenesis to identify mammalian factors contributing to toxin activity, including caveolin-2 (CAV2). In this study, we demonstrate the importance of caveolin-2 and its interaction partner, caveolin-1 (CAV1), in ε-toxin-induced cytotoxicity. Using CAV2-specific shRNA in a toxin-sensitive human kidney cell line, ACHN, we confirmed that cells deficient in CAV2 exhibit increased resistance to ε-toxin. Similarly, using CAV1-specific shRNA, we demonstrate that cells deficient in CAV1 also exhibit increased resistance to the toxin. Immunoprecipitation of CAV1 and CAV2 from ε-toxin-treated ACHN cells demonstrated interaction of both CAV1 and -2 with the toxin. Furthermore, blue-native PAGE indicated that the toxin and caveolins were components of a 670 kDa protein complex. Although ε-toxin binding was only slightly perturbed in caveolin-deficient cells, oligomerization of the toxin was dramatically reduced in both CAV1- and CAV2-deficient cells. These results indicate that CAV1 and -2 potentiate ε-toxin induced cytotoxicity by promoting toxin oligomerization - an event which is requisite for pore formation and, by extension, cell death.

Analysis of the common deletions in the mitochondrial DNA is a sensitive biomarker detecting direct and non-targeted cellular effects of low dose ionizing radiation.

PubMed

Schilling-Tóth, Boglárka; Sándor, Nikolett; Kis, Eniko; Kadhim, Munira; Sáfrány, Géza; Hegyesi, Hargita

2011-11-01

One of the key issues of current radiation research is the biological effect of low doses. Unfortunately, low dose science is hampered by the unavailability of easily performable, reliable and sensitive quantitative biomarkers suitable detecting low frequency alterations in irradiated cells. We applied a quantitative real time polymerase chain reaction (qRT-PCR) based protocol detecting common deletions (CD) in the mitochondrial genome to assess direct and non-targeted effects of radiation in human fibroblasts. In directly irradiated (IR) cells CD increased with dose and was higher in radiosensitive cells. Investigating conditioned medium-mediated bystander effects we demonstrated that low and high (0.1 and 2Gy) doses induced similar levels of bystander responses and found individual differences in human fibroblasts. The bystander response was not related to the radiosensitivity of the cells. The importance of signal sending donor and signal receiving target cells was investigated by placing conditioned medium from a bystander response positive cell line (F11-hTERT) to bystander negative cells (S1-hTERT) and vice versa. The data indicated that signal sending cells are more important in the medium-mediated bystander effect than recipients. Finally, we followed long term effects in immortalized radiation sensitive (S1-hTERT) and normal (F11-hTERT) fibroblasts up to 63 days after IR. In F11-hTERT cells CD level was increased until 35 days after IR then reduced back to control level by day 49. In S1-hTERT cells the increased CD level was also normalized by day 42, however a second wave of increased CD incidence appeared by day 49 which was maintained up to day 63 after IR. This second CD wave might be the indication of radiation-induced instability in the mitochondrial genome of S1-hTERT cells. The data demonstrated that measuring CD in mtDNA by qRT-PCR is a reliable and sensitive biomarker to estimate radiation-induced direct and non-targeted effects. Copyright © 2011 Elsevier B.V. All rights reserved.

Developmental plasticity in vision and behavior may help guppies overcome increased turbidity.

PubMed

Ehlman, Sean M; Sandkam, Benjamin A; Breden, Felix; Sih, Andrew

2015-12-01

Increasing turbidity in streams and rivers near human activity is cause for environmental concern, as the ability of aquatic organisms to use visual information declines. To investigate how some organisms might be able to developmentally compensate for increasing turbidity, we reared guppies (Poecilia reticulata) in either clear or turbid water. We assessed the effects of developmental treatments on adult behavior and aspects of the visual system by testing fish from both developmental treatments in turbid and clear water. We found a strong interactive effect of rearing and assay conditions: fish reared in clear water tended to decrease activity in turbid water, whereas fish reared in turbid water tended to increase activity in turbid water. Guppies from all treatments decreased activity when exposed to a predator. To measure plasticity in the visual system, we quantified treatment differences in opsin gene expression of individuals. We detected a shift from mid-wave-sensitive opsins to long wave-sensitive opsins for guppies reared in turbid water. Since long-wavelength sensitivity is important in motion detection, this shift likely allows guppies to salvage motion-detecting abilities when visual information is obscured in turbid water. Our results demonstrate the importance of developmental plasticity in responses of organisms to rapidly changing environments.

Bilirubin Increases Insulin Sensitivity in Leptin-Receptor Deficient and Diet-Induced Obese Mice Through Suppression of ER Stress and Chronic Inflammation

PubMed Central

Dong, Huansheng; Huang, Hu; Yun, Xinxu; Kim, Do-sung; Yue, Yinan; Wu, Hongju; Sutter, Alton; Chavin, Kenneth D.; Otterbein, Leo E.; Adams, David B.; Kim, Young-Bum

2014-01-01

Obesity-induced endoplasmic reticulum (ER) stress causes chronic inflammation in adipose tissue and steatosis in the liver, and eventually leads to insulin resistance and type 2 diabetes (T2D). The goal of this study was to understand the mechanisms by which administration of bilirubin, a powerful antioxidant, reduces hyperglycemia and ameliorates obesity in leptin-receptor-deficient (db/db) and diet-induced obese (DIO) mouse models. db/db or DIO mice were injected with bilirubin or vehicle ip. Blood glucose and body weight were measured. Activation of insulin-signaling pathways, expression of inflammatory cytokines, and ER stress markers were measured in skeletal muscle, adipose tissue, and liver of mice. Bilirubin administration significantly reduced hyperglycemia and increased insulin sensitivity in db/db mice. Bilirubin treatment increased protein kinase B (PKB/Akt) phosphorylation in skeletal muscle and suppressed expression of ER stress markers, including the 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein, X box binding protein (XBP-1), and activating transcription factor 4 in db/db mice. In DIO mice, bilirubin treatment significantly reduced body weight and increased insulin sensitivity. Moreover, bilirubin suppressed macrophage infiltration and proinflammatory cytokine expression, including TNF-α, IL-1β, and monocyte chemoattractant protein-1, in adipose tissue. In liver and adipose tissue of DIO mice, bilirubin ameliorated hepatic steatosis and reduced expression of GRP78 and C/EBP homologous protein. These results demonstrate that bilirubin administration improves hyperglycemia and obesity by increasing insulin sensitivity in both genetically engineered and DIO mice models. Bilirubin or bilirubin-increasing drugs might be useful as an insulin sensitizer for the treatment of obesity-induced insulin resistance and type 2 diabetes based on its profound anti-ER stress and antiinflammatory properties. PMID:24424052

Improving sensitivity of gold nanoparticle based fluorescence quenching and colorimetric aptasensor by using water resuspended gold nanoparticle.

PubMed

Liu, Jinchuan; Guan, Zheng; Lv, Zhenzhen; Jiang, Xiaoling; Yang, Shuming; Chen, Ailiang

2014-02-15

Gold nanoparticles (AuNPs) based fluorescence quenching or colorimetric aptasensor have been developed for many analytes recently largely because of the ease of detection, high sensitivity, and potential for high-throughput analysis. However, the effects of remnant non-AuNPs components in the colloid gold solution on these assays performance remain unclear. For the first time, we demonstrated that the remnant sodium citrate and the reaction products of three acids play counteractive roles in AuNPs based fluorescence quenching and colorimetric aptasensor in three ways in this study. First, the remnant sodium citrate in the colloid gold solution could increase the fluorescence intensity of FAM labeled on the aptamer that reduce the efficiency of AuNPs fluorescent quenching. Second, the reaction products of citric acid, HCl and ketoglutaric acid reduce the fluorescence recovery by quenching the fluorescence of FAM labeled on the aptamer dissociated from the surface of AuNPs upon addition of target. Lastly, the reaction products of three acids reduce the pH value of the colloid gold solution that reduce the sensitivity of AuNPs based colorimetric aptasensor by increasing the adsorption of aptamer to surface of AuNPs. With sulfadimethoxine and thrombin as model analytes, we found that water resuspended AuNPs can significantly increase the sensitivity by more than 10-fold for AuNPs based fluorescence quenching aptasensor. In the AuNPs based colorimetric aptasensor for sulfadimethoxine using the water resuspended AuNPs, the sensitivity also was increased by 10-fold compared with that of original AuNPs. The findings in this study provide theoretical guidance for further improving AuNPs based fluorescent quenching and colorimetric aptasensor by adjusting the composition of AuNPs solution. © 2013 Elsevier B.V. All rights reserved.

The hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is sensitive to sex differences

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

Wyeth, Richard P.; Division of Physiology, Virginia College of Osteopathic Medicine, Blacksburg, VA 24060; Mills, Edward M.

Female subjects have been reported to be less sensitive to the hyperthermic effects of 3,4-methylenedioxymethamine (MDMA) than males. Studies were designed to examine the cellular mechanisms involved in these sex sensitive differences. Gonadectomized female and male rats were treated with a 200 {mu}g 100 {mu}L{sup -1} of estrogen or 100 {mu}g 100 {mu}L{sup -1} of testosterone respectively every 5 days for a total of three doses. Rats were then challenged with either saline or MDMA (20 mg kg{sup -1}, sc). Rats were then euthanized and aortas were constricted, in vitro, by serial phenylephrine (Phe) addition with or without the inhibitormore » of nitric oxide (NO) synthase, g-nitro-L-Arginine-Methyl Ester (L-NAME). Skeletal muscle uncoupling protein-3 (UCP3) expression was measured as well as plasma norepinephrine (NE) levels. All males but no females developed hyperthermia following MDMA treatment. The EC{sub 50} for Phe dose response curves increased only in the females treated with MDMA and T{sub max} for Phe increased following L-NAME only in the females. Both males and females demonstrated an increase in plasma NE following MDMA treatment; however, males displayed a significantly greater NE concentration. Skeletal muscle UCP3 expression was 80% less in females than in males. These results suggest that the inability of MDMA to induce a thermogenic response in the female subjects may be due to four sex-specific mechanisms: 1) Female subjects have reduced sympathetic activation following MDMA challenge; 2) Female vasculature is less sensitive to {alpha}{sub 1}-AR stimulation following MDMA challenge; 3) Female vasculature has an increased sensitivity to NO; 4) UCP3 expression in skeletal muscle is less in females.« less

On the origin of increased sensitivity and mass resolution using silicon masks in MALDI.

PubMed

Diologent, Laurent; Franck, Julien; Wisztorski, Maxence; Treizebre, Anthony; Focsa, Cristian; Fournier, Isabelle; Ziskind, Michael

2014-02-04

Since its development, MALDI has proved its performance in the analysis of intact biomolecules up to high molecular weights, regardless of their polarity. Sensitivity of MALDI instruments is a key point for breaking the limits of observing biomolecules of lower abundances. Instrumentation is one way to improve sensitivity by increasing ion transmission and using more sensitive detection systems. On the other side, improving MALDI ion production yields would have important outcomes. MALDI ion production is still not well-controlled and, indeed, the amount of ions produced per laser shot with respect to the total volume of desorbed material is very low. This has particular implications for certain applications, such as MALDI MS imaging where laser beam focusing as fine as possible (5-10 μm) is searched in order to reach higher spatial resolution images. However, various studies point out an intrinsic decrease in signal intensity for strong focusing. We have therefore been interested in developing silicon mask systems to decrease an irradiated area by cutting rather than focusing the laser beam and to study the parameters affecting sensitivity using such systems. For this, we systematically examined variation with laser fluence of intensity and spectral resolution in MALDI of standard peptides when using silicon-etched masks of various aperture sizes. These studies demonstrate a simultaneous increase in spectral resolution and signal intensity. Origin of this effect is discussed in the frame of the two-step ionization model. Experimental data in the low fluence range are fitted with an increase of the primary ionization through matrix-silicon edge contact provided by the masks. On the other hand, behavior at higher fluence could be explained by an effect on the secondary ionization via changes in the plume dynamics.

Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

PubMed Central

van der Zijl, Nynke J.; Moors, Chantalle C.M.; Goossens, Gijs H.; Hermans, Marc M.H.; Blaak, Ellen E.; Diamant, Michaela

2011-01-01

OBJECTIVE Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P < 0.001). BMI remained unchanged in both treatment groups (P = 0.89). CONCLUSIONS Twenty-six weeks of valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes. PMID:21330640

Multienzyme-nanoparticles amplification for sensitive virus genotyping in microfluidic microbeads array using Au nanoparticle probes and quantum dots as labels.

PubMed

Zhang, He; Liu, Lian; Li, Cheuk-Wing; Fu, Huayang; Chen, Yao; Yang, Mengsu

2011-11-15

A novel microfluidic device with microbeads array was developed and sensitive genotyping of human papillomavirus was demonstrated using a multiple-enzyme labeled oligonucleotide-Au nanoparticle bioconjugate as the detection tool. This method utilizes microbeads as sensing platform that was functionalized with the capture probes and modified electron rich proteins, and uses the horseradish peroxidase (HRP)-functionalized gold nanoparticles as label with a secondary DNA probe. The functionalized microbeads were independently introduced into the arrayed chambers using the loading chip slab. A single channel was used to generate weir structures to confine the microbeads and make the beads array accessible by microfluidics. Through "sandwich" hybridization, the enzyme-functionalized Au nanoparticles labels were brought close to the surface of microbeads. The oxidation of biotin-tyramine by hydrogen peroxide resulted in the deposition of multiple biotin moieties onto the surface of beads. This deposition is markedly increased in the presence of immobilized electron rich proteins. Streptavidin-labeled quantum dots were then allowed to bind to the deposited biotin moieties and displayed the signal. Enhanced detection sensitivity was achieved where the large surface area of Au nanoparticle carriers increased the amount HRP bound per sandwiched hybridization. The on-chip genotyping method could discriminate as low as 1fmol/L (10zmol/chip, SNR>3) synthesized HPV oligonucleotides DNA. The chip-based signal enhancement of the amplified assay resulted in 1000 times higher sensitivity than that of off-chip test. In addition, this on-chip format could discriminate and genotype 10copies/μL HPV genomic DNA using the PCR products. These results demonstrated that this on-chip approach can achieve highly sensitive detection and genotyping of target DNA and can be further developed for detection of disease-related biomolecules at the lowest level at their earliest incidence. Copyright © 2011 Elsevier B.V. All rights reserved.

Food odors trigger an endocrine response that affects food ingestion and metabolism.

PubMed

Lushchak, Oleh V; Carlsson, Mikael A; Nässel, Dick R

2015-08-01

Food odors stimulate appetite and innate food-seeking behavior in hungry animals. The smell of food also induces salivation and release of gastric acid and insulin. Conversely, sustained odor exposure may induce satiation. We demonstrate novel effects of food odors on food ingestion, metabolism and endocrine signaling in Drosophila melanogaster. Acute exposure to attractive vinegar odor triggers a rapid and transient increase in circulating glucose, and a rapid upregulation of genes encoding the glucagon-like hormone adipokinetic hormone (AKH), four insulin-like peptides (DILPs) and some target genes in peripheral tissues. Sustained exposure to food odors, however, decreases food intake. Hunger-induced strengthening of synaptic signaling from olfactory sensory neurons (OSNs) to brain neurons increases food-seeking behavior, and conversely fed flies display reduced food odor sensitivity and feeding. We show that increasing the strength of OSN signaling chronically by genetic manipulation of local peptide neuromodulation reduces feeding, elevates carbohydrates and diminishes lipids. Furthermore, constitutively strengthened odor sensitivity altered gene transcripts for AKH, DILPs and some of their targets. Thus, we show that food odor can induce a transient anticipatory endocrine response, and that boosted sensitivity to this odor affects food intake, as well as metabolism and hormonal signaling.

Fundamental study of flow field generated by rotorcraft blades using wide-field shadowgraph

NASA Technical Reports Server (NTRS)

Parthasarathy, S. P.; Cho, Y. I.; Back, L. H.

1985-01-01

The vortex trajectory and vortex wake generated by helicopter rotors are visualized using a wide-field shadowgraph technique. Use of a retro-reflective Scotchlite screen makes it possible to investigate the flow field generated by full-scale rotors. Tip vortex trajectories are visible in shadowgraphs for a range of tip Mach number of 0.38 to 0.60. The effect of the angle of attack is substantial. At an angle of attack greater than 8 degrees, the visibility of the vortex core is significant even at relatively low tip Mach numbers. The theoretical analysis of the sensitivity is carried out for a rotating blade. This analysis demonstrates that the sensitivity decreases with increasing dimensionless core radius and increases with increasing tip Mach number. The threshold value of the sensitivity is found to be 0.0015, below which the vortex core is not visible and above which it is visible. The effect of the optical path length is also discussed. Based on this investigation, it is concluded that the application of this wide-field shadowgraph technique to a large wind tunnel test should be feasible. In addition, two simultaneous shadowgraph views would allow three-dimensional reconstruction of vortex trajectories.

Validation of Version 3.0 of the Breast Cancer Genetics Referral Screening Tool (B-RST™).

PubMed

Bellcross, Cecelia; Hermstad, April; Tallo, Christine; Stanislaw, Christine

2018-05-08

Despite increased awareness of hereditary breast and ovarian cancer among clinicians and the public, many BRCA1/2 mutation carriers remain unaware of their risk status. The Breast Cancer Genetics Referral Screening Tool (B-RST™) was created and validated to easily identify individuals at increased risk for hereditary breast and ovarian cancer for referral to cancer genetics services. The purpose of this study was to revise B-RST™ to maximize sensitivity against BRCA1/2 mutation status. We analyzed pedigrees of 277 individuals who had undergone BRCA1/2 testing to determine modifications to the B-RST™ 2.0 algorithm that would maximize sensitivity for mutations, while maintaining simplicity. We used McNemar's chi-square test to compare validation measures between the revised version (3.0) and the 2.0 version. Algorithmic changes made to B-RST™ 2.0 increased the sensitivity against BRCA1/2 mutation analysis from 71.1 to 94.0% (P < 0.0001). While specificity decreased, all screen-positive individuals were appropriate for cancer genetics referral, the primary purpose of the tool. Despite calls for BRCA1/2 population screening, there remains a critical need to identify those most at risk who should receive cancer genetics services. B-RST™ version 3.0 demonstrates high sensitivity for BRCA1/2 mutations, yet remains a simple and quick screening tool for at-risk individuals.

Antiobesity Effect of a Small Molecule Repressor of RORγ

PubMed Central

Chang, Mi Ra; He, Yuanjun; Khan, Tanya M.; Kuruvilla, Dana S.; Garcia-Ordonez, Ruben; Corzo, Cesar A.; Unger, Thaddeus J.; White, David W.; Khan, Susan; Lin, Li; Cameron, Michael D.; Kamenecka, Theodore M.

2015-01-01

The orphan nuclear receptor RORγ is a key regulator for T helper 17 (TH17) cell differentiation, which regulates metabolic and circadian rhythm genes in peripheral tissues. Previously, it was shown that the small molecule inverse agonist of RORγ SR1555 [1-(4-((4′-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-[1,1′-biphenyl]-4-yl)methyl)piperazin-1-yl) ethanone] suppressed TH17 differentiation and stimulated induced T regulatory (iTreg) cells. Here, we show that treatment of cultured pre-adipocyctes with SR1555 represses the expression of RORγ while leading to increased expression of FGF21 and adipoQ. Chronic administration of SR1555 to obese diabetic mice resulted in a modest reduction in food intake accompanied with significant reduction in fat mass, resulting in reduced body weight and improved insulin sensitivity. Analysis ex vivo of treated mice demonstrates that SR1555 induced expression of the thermogenic gene program in fat depots. Further studies in cultured cells showed that SR1555 inhibited activation of hormone-sensitive lipase and increased fatty acid oxidation. Combined, these results suggest that pharmacological repression of RORγ may represent a strategy for treatment of obesity by increasing thermogenesis and fatty acid oxidation, while inhibition of hormone-sensitive lipase activity results in a reduction of serum free fatty acids, leading to improved peripheral insulin sensitivity. PMID:25904554

Curcumin increases the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction.

PubMed

Lu, Yimin; Wang, Jun; Liu, Lei; Yu, Lequn; Zhao, Nian; Zhou, Xingju; Lu, Xudong

2017-04-01

Non-small-cell lung cancer is one of the most lethal cancers in the worldwide. Although Paclitaxel-based combinational therapies have long been used as a standard treatment in aggressive non-small-cell lung cancers, Paclitaxel resistance emerges as a major clinical problem. It has been demonstrated that Curcumin from Curcuma longa as a traditional Chinese medicine can inhibit cancer cell proliferation. However, the role of Curcumin in Paclitaxel-resistant non-small-cell lung cancer cells is not clear. In this study, we investigated the effect of Curcumin on the Paclitaxel-resistant non-small-cell lung cancer cells and found that Curcumin treatment markedly increased the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel. Mechanically, the study revealed that Curcumin could reduce the expression of metastasis-associated gene 1 (MTA1) gene through upregulation of microRNA-30c in Paclitaxel-resistant non-small-cell lung cancer cells. During the course, MTA1 reduction sensitized Paclitaxel-resistant non-small-cell lung cancer cells and enhanced the effect of Paclitaxel. Taken together, our studies indicate that Curcumin increases the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction. Curcumin might be a potential adjuvant for non-small-cell lung cancer patients during Paclitaxel treatment.

Beneficial effect of baicalin on insulin sensitivity in adipocytes of diet-induced obese mice.

PubMed

Fang, Penghua; Yu, Mei; Min, Wen; Han, Shiyu; Shi, Mingyi; Zhang, Zhenwen; Bo, Ping

2018-05-01

Although baicalin has been shown to increase glucose uptake and insulin sensitivity in skeletal muscle of mice, there is no literature available about the effect of baicalin on insulin sensitivity in adipocytes of diet-induced obese mice. In the present study, diet-induced obese mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 days, and 3T3-L1 cells were treated with 100, 200, 400 μM baicalin for 3 h. Then insulin resistance indexes and insulin signal protein levels were examined to elucidate whether baicalin increased glucose uptake and GLUT4 translocation in adipocytes of diet-induced obese mice. The present findings showed that administration of baicalin decreased food intake, body weight, HOMA-IR and p-p38 MAPK and pERK levels, but enhanced pAKT and PGC-1α contents, as well as GLUT4 mRNA, PGC-1α mRNA expression in adipocytes, and reversed high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Moreover, baicalin treatment increased GLUT4 concentration in plasma membranes of adipocytes. These data demonstrated that baicalin accelerated GLUT4 translocation from intracellular membrane compartments to plasma membranes in adipocytes. Baicalin plays a significant role in elevation of glucose uptake and insulin sensitivity to promote glucose clearance. Copyright © 2018 Elsevier B.V. All rights reserved.

Electrolytic lesions of the nucleus accumbens core (but not the medial shell) and the basolateral amygdala enhance context-specific locomotor sensitization to nicotine in rats.

PubMed

Kelsey, John E; Gerety, Lyle P; Guerriero, Rejean M

2009-06-01

We previously demonstrated that lesions of the nucleus accumbens (NAc) core enhanced locomotion and locomotor sensitization to repeated injections of nicotine in rats (Kelsey & Willmore, 2006). In this study, we compared the effects of separate lesions of the NAc core, NAc medial shell, and basolateral amygdala on context-specific locomotor sensitization to repeated injections of 0.4 mg/kg nicotine. Electrolytic lesions of the NAc core increased locomotion, and lesions of the core (but not the shell) and the basolateral amygdala enhanced context-specific locomotor sensitization by enhancing the development of sensitization in paired rats and decreasing expression in unpaired rats relative to sham-operated rats when challenged with an injection of 0.4 mg/kg nicotine in the locomotor chambers. These data are consistent with findings that the NAc core and the basolateral amygdala share a variety of behavioral functions and anatomical connections. The findings that lesions of these structures enhance context-specific locomotor sensitization while typically impairing other reward-related behaviors also indicate that the processes underlying locomotor sensitization and reward are not identical. Copyright (c) 2009 APA, all rights reserved.

Utilization of the ex vivo LLNA: BrdU-ELISA to distinguish the sensitizers from irritants in respect of 3 end points-lymphocyte proliferation, ear swelling, and cytokine profiles.

PubMed

Arancioglu, Seren; Ulker, Ozge Cemiloglu; Karakaya, Asuman

2015-01-01

Dermal exposure to chemicals may result in allergic or irritant contact dermatitis. In this study, we performed ex vivo local lymph node assay: bromodeoxyuridine-enzyme-linked immunosorbent assay (LLNA: BrdU-ELISA) to compare the differences between irritation and sensitization potency of some chemicals in terms of the 3 end points: lymphocyte proliferation, cytokine profiles (interleukin 2 [IL-2], interferon-γ (IFN-γ), IL-4, IL-5, IL-1, and tumor necrosis factor α [TNF-α]), and ear swelling. Different concentrations of the following well-known sensitizers and irritant chemicals were applied to mice: dinitrochlorobenzene, eugenol, isoeugenol, sodium lauryl sulfate (SLS), and croton oil. According to the lymph node results; the auricular lymph node weights and lymph node cell counts increased after application of both sensitizers and irritants in high concentrations. On the other hand, according to lymph node cell proliferation results, there was a 3-fold increase in proliferation of lymph node cells (stimulation index) for sensitizer chemicals and SLS in the applied concentrations; however, there was not a 3-fold increase for croton oil and negative control. The SLS gave a false-positive response. Cytokine analysis demonstrated that 4 cytokines including IL-2, IFN-γ, IL-4, and IL-5 were released in lymph node cell cultures, with a clear dose trend for sensitizers whereas only TNF-α was released in response to irritants. Taken together, our results suggest that the ex vivo LLNA: BrdU-ELISA method can be useful for discriminating irritants and allergens. © The Author(s) 2015.

Short-chain C6 ceramide sensitizes AT406-induced anti-pancreatic cancer cell activity

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

Zhao, Xiaoguang; Sun, Baoyou; Zhang, Jingjing

Our previous study has shown that AT406, a first-in-class small molecular antagonist of IAPs (inhibitor of apoptosis proteins), inhibits pancreatic cancer cell proliferation in vitro and in vivo. The aim of this research is to increase AT406's sensitivity by adding short-chain C6 ceramide. We show that co-treatment of C6 ceramide dramatically potentiated AT406-induced caspase/apoptosis activation and cytotoxicity in established (Panc-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells. Reversely, caspase inhibitors largely attenuated C6 ceramide plus AT406-induced above cancer cell death. Molecularly, C6 ceramide downregulated Bcl-2 to increase AT406's sensitivity in pancreatic cancer cells. Intriguingly, C6 ceramide-mediated AT406 sensitization was nullifiedmore » with Bcl-2 shRNA knockdown or pretreatment of the Bcl-2 inhibitor ABT-737. In vivo, liposomal C6 ceramide plus AT406 co-administration dramatically inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) mice. The combined anti-tumor activity was significantly more potent than either single treatment. Expressions of IAPs (cIAP1/XIAP) and Bcl-2 were downregulated in Panc-1 xenografts with the co-administration. Together, we demonstrate that C6 ceramide sensitizes AT406-mediated anti-pancreatic cancer cell activity possibly via downregulating Bcl-2. - Highlights: • C6 ceramide dramatically potentiates AT406-induced pancreatic cancer cell death. • C6 ceramide facilitates AT406-induced pancreatic cancer cell apoptosis. • C6 ceramide downregulates Bcl-2 to increase AT406's sensitivity in pancreatic cancer cells. • Liposomal C6 ceramide enhances AT406-induced anti-pancreatic cancer activity in vivo.« less

Polychromatic Light (480-3400 nm) Upregulates Sensitivity of Tumor Cells to Lysis by Natural Killers.

PubMed

Knyazev, Nickolay A; Samoilova, Kira A; Abrahamse, Heidi; Filatova, Natalia A

2016-09-01

This study evaluates the participation of immunological mechanisms of downregulation of murine hepatoma cells MH22a after direct exposure to polychromatic polarized light. Previous studies have shown that exposure to a combination of visible (VIS) and infrared (IR) light leads to decreased tumorigenicity of the murine hepatoma cells MH22a, which correlated with an increase in the amount of cells with reorganized cytoskeleton in the submembrane region. The mechanism of tumor inhibition and elimination has not been determined. Polychromatic light (480-3400 nm) has been used at doses of 4.8 and 9.6 J/cm(2) to determine the sensitivity of murine MH22a cells and human erythroleukemia cells K562 exposed to this light, to lysis by effector cells of innate immunity (NK cells), and enhancement of the glycocalyx of the studied tumor cells. This was determined using flow cytometry, the H(3)-uridine cytotoxic test followed by spectrophotometry. VIS-IR light increases the sensitivity of MH-22a cells at a dose 4.8 J/cm(2) and K562 cells at 9.6 J/cm(2). The enhancement of sensitivity of tumor cells to NK lysis changed their ability to absorb alcian blue, reflecting a change in the expression of the glycocalyx. Increasing the sensitivity of the murine tumor cells MH22a and human K562 irradiated VIS-IR light correlated with a change in the expression of their glycocalyx. The results of the present study demonstrate that the reduction of tumorigenicity of irradiated tumor cells is due to their sensitivity to lysis by NK cells of the immune system.

A two-fold increase of carbon cycle sensitivity to tropical temperature variations.

PubMed

Wang, Xuhui; Piao, Shilong; Ciais, Philippe; Friedlingstein, Pierre; Myneni, Ranga B; Cox, Peter; Heimann, Martin; Miller, John; Peng, Shushi; Wang, Tao; Yang, Hui; Chen, Anping

2014-02-13

Earth system models project that the tropical land carbon sink will decrease in size in response to an increase in warming and drought during this century, probably causing a positive climate feedback. But available data are too limited at present to test the predicted changes in the tropical carbon balance in response to climate change. Long-term atmospheric carbon dioxide data provide a global record that integrates the interannual variability of the global carbon balance. Multiple lines of evidence demonstrate that most of this variability originates in the terrestrial biosphere. In particular, the year-to-year variations in the atmospheric carbon dioxide growth rate (CGR) are thought to be the result of fluctuations in the carbon fluxes of tropical land areas. Recently, the response of CGR to tropical climate interannual variability was used to put a constraint on the sensitivity of tropical land carbon to climate change. Here we use the long-term CGR record from Mauna Loa and the South Pole to show that the sensitivity of CGR to tropical temperature interannual variability has increased by a factor of 1.9 ± 0.3 in the past five decades. We find that this sensitivity was greater when tropical land regions experienced drier conditions. This suggests that the sensitivity of CGR to interannual temperature variations is regulated by moisture conditions, even though the direct correlation between CGR and tropical precipitation is weak. We also find that present terrestrial carbon cycle models do not capture the observed enhancement in CGR sensitivity in the past five decades. More realistic model predictions of future carbon cycle and climate feedbacks require a better understanding of the processes driving the response of tropical ecosystems to drought and warming.

Tree density and permafrost thaw depth influence water limitations on stomatal conductance in Siberian Arctic boreal forests

NASA Astrophysics Data System (ADS)

Kropp, H.; Loranty, M. M.; Natali, S.; Kholodov, A. L.; Alexander, H. D.; Zimov, N.

2017-12-01

Boreal forests may experience increased water stress under global climate change as rising air temperatures increase evaporative demand and decrease soil moisture. Increases in plant water stress can decrease stomatal conductance, and ultimately, decrease primary productivity. A large portion of boreal forests are located in Siberia, and are dominated by deciduous needleleaf trees, Larix spp. We investigated the variability and drivers of canopy stomatal conductance in upland Larix stands with different stand density that arose from differing fire severity. Our measurements focus on an open canopy stand with low tree density and deep permafrost thaw depth, and a closed canopy stand with high tree density and shallow permafrost thaw depth. We measured canopy stomatal conductance, soil moisture, and micrometeorological variables. Our results demonstrate that canopy stomatal conductance was significantly lower in the closed canopy stand with a significantly higher sensitivity to increases in atmospheric evaporative demand. Canopy stomatal conductance in both stands was tightly coupled to precipitation that occurred over the previous week; however, the closed canopy stand showed a significantly greater sensitivity to increases in precipitation compared to the open canopy stand. Differences in access to deep versus shallow soil moisture and the physical characteristics of the soil profile likely contribute to differences in sensitivity to precipitation between the two stands. Our results indicate that Larix primary productivity may be highly sensitive to changes in evaporative demand and soil moisture that can result of global climate change. However, the effect of increasing air temperatures and changes in precipitation will differ significantly depending on stand density, thaw depth, and the hydraulic characteristics of the soil profile.

Investigation of Blade Impulsive Noise on a Scaled Fully Articulated Rotor System

NASA Technical Reports Server (NTRS)

Scheiman, James; Hoad, Danny R.

1977-01-01

Helicopter impulsive noise tests were conducted in the Langley V/STOL tunnel with an articulated rotor system. The tests demonstrated that impulsive noise could be simulated for low-speed forward flight with low descent rates and also in the high-speed level flight. For the low forward speed condition, the noise level was highly sensitive to small changes in descent rate. For the high-speed condition, the noise level was increased with an increase in rotor thrust.

Combined high contrast and wide field of view in the scanning laser ophthalmoscope through dual detection of light paths

NASA Astrophysics Data System (ADS)

Carles, Guillem; Muyo, Gonzalo; van Hemert, Jano; Harvey, Andrew R.

2017-11-01

We demonstrate a multimode detection system in a scanning laser ophthalmoscope (SLO) that enables simultaneous operation in confocal, indirect, and direct modes to permit an agile trade between image contrast and optical sensitivity across the retinal field of view to optimize the overall imaging performance, enabling increased contrast in very wide-field operation. We demonstrate the method on a wide-field SLO employing a hybrid pinhole at its image plane, to yield a twofold increase in vasculature contrast in the central retina compared to its conventional direct mode while retaining high-quality imaging across a wide field of the retina, of up to 200 deg and 20 μm on-axis resolution.

Overexpression of xeroderma pigmentosum group C decreases the chemotherapeutic sensitivity of colorectal carcinoma cells to cisplatin.

PubMed

Zhang, Yi; Cao, Jia; Meng, Yanni; Qu, Chunying; Shen, Feng; Xu, Leiming

2018-05-01

Xeroderma pigmentosum group C (XPC) is a DNA-damage-recognition gene active at the early stage of DNA repair. XPC also participates in regulation of cell-cycle checkpoint and DNA-damage-induced apoptosis. In the present study, the expression levels of genes involved in nucleotide excision repair (NER) were assessed in human colorectal cancer (CRC) tissue. This analysis revealed that expression of XPC mRNA significantly increased in colorectal carcinoma tissues compared with matched normal controls. Expression of XPC gradually increased along with the degree of progression of CRC. In vitro , an XTT assay demonstrated that small interfering RNA (siRNA) targeting XPC significantly increased the sensitivity of CRC SW480 cells to cisplatin, whereas cells transfected with a XPC-overexpression plasmid became more resistant to cisplatin. Furthermore, flow cytometry revealed that the proportion of apoptotic cells significantly increased in XPC-knockdown cells upon cisplatin treatment. However, the overexpression XPC significantly increased the resistance of cells to cisplatin. In vivo , tumor growth was significantly reduced in tumor-bearing mice when the XPC gene was knocked down. Upregulation of the expression of pro-apoptotic Bcl-associated X and downregulation of the anti-apoptotic B-cell lymphoma 2 proteins was observed in the implanted tumor tissue. In conclusion, XPC serves a key role in chemotherapeutic sensitivity of CRC to cisplatin, meaning that it may be a potential target for chemotherapy of CRC.

FIACH: A biophysical model for automatic retrospective noise control in fMRI.

PubMed

Tierney, Tim M; Weiss-Croft, Louise J; Centeno, Maria; Shamshiri, Elhum A; Perani, Suejen; Baldeweg, Torsten; Clark, Christopher A; Carmichael, David W

2016-01-01

Different noise sources in fMRI acquisition can lead to spurious false positives and reduced sensitivity. We have developed a biophysically-based model (named FIACH: Functional Image Artefact Correction Heuristic) which extends current retrospective noise control methods in fMRI. FIACH can be applied to both General Linear Model (GLM) and resting state functional connectivity MRI (rs-fcMRI) studies. FIACH is a two-step procedure involving the identification and correction of non-physiological large amplitude temporal signal changes and spatial regions of high temporal instability. We have demonstrated its efficacy in a sample of 42 healthy children while performing language tasks that include overt speech with known activations. We demonstrate large improvements in sensitivity when FIACH is compared with current methods of retrospective correction. FIACH reduces the confounding effects of noise and increases the study's power by explaining significant variance that is not contained within the commonly used motion parameters. The method is particularly useful in detecting activations in inferior temporal regions which have proven problematic for fMRI. We have shown greater reproducibility and robustness of fMRI responses using FIACH in the context of task induced motion. In a clinical setting this will translate to increasing the reliability and sensitivity of fMRI used for the identification of language lateralisation and eloquent cortex. FIACH can benefit studies of cognitive development in young children, patient populations and older adults. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Design and Development of 256x256 Linear Mode Low-Noise Avalanche Photodiode Arrays

NASA Technical Reports Server (NTRS)

Yuan, Ping; Sudharsanan, Rengarajan; Bai, Xiaogang; Boisvert, Joseph; McDonald, Paul; Chang, James

2011-01-01

A larger format photodiode array is always desirable for many LADAR imaging applications. However, as the array format increases, the laser power or the lens aperture has to increase to maintain the same flux per pixel thus increasing the size, weight and power of the imaging system. In order to avoid this negative impact, it is essential to improve the pixel sensitivity. The sensitivity of a short wavelength infrared linear-mode avalanche photodiode (APD) is a delicate balance of quantum efficiency, usable gain, excess noise factor, capacitance, and dark current of APD as well as the input equivalent noise of the amplifier. By using InA1As as a multiplication layer in an InP-based APD, the ionization coefficient ratio, k, is reduced from 0.40 (lnP) to 0.22, and the excess noise is reduced by about 50%. An additional improvement in excess noise of 25% was achieved by employing an impact-ionization-engineering structure with a k value of 0.15. Compared with the traditional InP structure, about 30% reduction in the noise-equivalent power with the following amplifier can be achieved. Spectrolab demonstrated 30-um mesa APD pixels with a dark current less than 10 nA and a capacitance of 60 fF at gain of 10. APD gain uninformity determines the usable gain of most pixels in an array, which is critical to focal plane array sensitivity. By fine tuning the material growth and device process, a break-down-voltage standard deviation of 0.1 V and gain of 30 on individual pixels were demonstrated in our 256x256 linear-mode APD arrays.

Implementation of Novel Design Features for qPCR-Based eDNA Assessment

PubMed Central

Veldhoen, Nik; Hobbs, Jared; Ikonomou, Georgios; Hii, Michael; Lesperance, Mary; Helbing, Caren C.

2016-01-01

Environmental stewardship requires timely, accurate information related to the status of a given ecosystem and the species that occupy it. Recent advances in the application of the highly sensitive real-time quantitative polymerase chain reaction (qPCR) towards identification of constituents within environmental DNA (eDNA) now allow targeted detection of the presence of species-specific biological material within a localized geographic region. However, as with all molecular techniques predicated on the specificity and sensitivity of the PCR assay, careful validation of each eDNA qPCR assay in development must be performed both under controlled laboratory conditions and when challenged with field-derived eDNA samples. Such a step-wise approach forms the basis for incorporation of innovative qPCR design features that strengthen the implementation and interpretation of the eDNA assay. This includes empirical determination that the qPCR assay is refractory to the presence of human DNA and the use of a tripartite assay approach comprised of 1) a primer set targeting plant chloroplast that evaluates the presence of amplifiable DNA from field samples to increase confidence in a negative result, 2) an animal group primer set to increase confidence in the assay result, and 3) a species-specific primer set to assess presence of DNA from the target species. To demonstrate this methodology, we generated eDNA assays specific for the North American bullfrog (Lithobates (Rana) catesbeiana) and the Rocky Mountain tailed frog (Ascaphus montanus) and characterized each with respect to detection sensitivity and specificity with demonstrated performance in a field survey scenario. The qPCR design features presented herein address specific challenges of eDNA assays thereby increasing their interpretative power. PMID:27802293

40 CFR 63.7833 - How do I demonstrate continuous compliance with the emission limitations that apply to me?

Code of Federal Regulations, 2010 CFR

2010-07-01

... baghouse equipped with a bag leak detection system, operating and maintaining each bag leak detection... requirements. If you increase or decrease the sensitivity of the bag leak detection system beyond the limits... event of a bag leak detection system alarm or when the hourly average opacity exceeded 5 percent, the...

Solid State Research

DTIC Science & Technology

1993-08-15

interferometric modulators has been shown [1 ],[2] to be affected by device annealing, with increased sensitivity demonstrated at annealing temperatures...changes in modulator performance. The measurements reported here were all made on Mach-Zehnder interferometric modula- tors fabricated on X-cut, Y...cooled under an arsine flow to the growth temperature used for InAs. The surface morphology of the InAs layers was examined by Nomarski contrast

Increasing productivity for the analysis of trace contaminants in food by gas chromatography-mass spectrometry using automated liner exchange, backflushing and heart-cutting.

PubMed

David, Frank; Tienpont, Bart; Devos, Christophe; Lerch, Oliver; Sandra, Pat

2013-10-25

Laboratories focusing on residue analysis in food are continuously seeking to increase sample throughput by minimizing sample preparation. Generic sample extraction methods such as QuEChERS lack selectivity and consequently extracts are not free from non-volatile material that contaminates the analytical system. Co-extracted matrix constituents interfere with target analytes, even if highly sensitive and selective GC-MS/MS is used. A number of GC approaches are described that can be used to increase laboratory productivity. These techniques include automated inlet liner exchange and column backflushing for preservation of the performance of the analytical system and heart-cutting two-dimensional GC for increasing sensitivity and selectivity. The application of these tools is illustrated by the analysis of pesticides in vegetables and fruits, PCBs in milk powder and coplanar PCBs in fish. It is demonstrated that considerable increase in productivity can be achieved by decreasing instrument down-time, while analytical performance is equal or better compared to conventional trace contaminant analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

Inhibition of the Electrostatic Interaction between β -amyloid Peptide and Membranes Prevents β -amyloid-induced Toxicity

NASA Astrophysics Data System (ADS)

Hertel, C.; Terzi, E.; Hauser, N.; Jakob-Rotne, R.; Seelig, J.; Kemp, J. A.

1997-08-01

The accumulation of β -amyloid peptides (Aβ ) into senile plaques is one of the hallmarks of Alzheimer disease. Aggregated Aβ is toxic to cells in culture and this has been considered to be the cause of neurodegeneration that occurs in the Alzheimer disease brain. The discovery of compounds that prevent Aβ toxicity may lead to a better understanding of the processes involved and ultimately to possible therapeutic drugs. Low nanomolar concentrations of Aβ 1-42 and the toxic fragment Aβ 25-35 have been demonstrated to render cells more sensitive to subsequent insults as manifested by an increased sensitivity to formazan crystals following MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction. Formation of the toxic β -sheet conformation by Aβ peptides is increased by negatively charged membranes. Here we demonstrate that phloretin and exifone, dipolar compounds that decrease the effective negative charge of membranes, prevent association of Aβ 1-40 and Aβ 25-35 to negatively charged lipid vesicles and Aβ induced cell toxicity. These results suggest that Aβ toxicity is mediated through a nonspecific physicochemical interaction with cell membranes.

The Case for Intelligent Propulsion Control for Fast Engine Response

NASA Technical Reports Server (NTRS)

Litt, Jonathan S.; Frederick, Dean K.; Guo, Ten-Huei

2009-01-01

Damaged aircraft have occasionally had to rely solely on thrust to maneuver as a consequence of losing hydraulic power needed to operate flight control surfaces. The lack of successful landings in these cases inspired research into more effective methods of utilizing propulsion-only control. That research demonstrated that one of the major contributors to the difficulty in landing is the slow response of the engines as compared to using traditional flight control. To address this, research is being conducted into ways of making the engine more responsive under emergency conditions. This can be achieved by relaxing controller limits, adjusting schedules, and/or redesigning the regulators to increase bandwidth. Any of these methods can enable faster response at the potential expense of engine life and increased likelihood of stall. However, an example sensitivity analysis revealed a complex interaction of the limits and the difficulty in predicting the way to achieve the fastest response. The sensitivity analysis was performed on a realistic engine model, and demonstrated that significantly faster engine response can be achieved compared to standard Bill of Material control. However, the example indicates the need for an intelligent approach to controller limit adjustment in order for the potential to be fulfilled.

Increasing the sensitivity of reverse phase protein arrays by antibody-mediated signal amplification

PubMed Central

2010-01-01

Background Reverse phase protein arrays (RPPA) emerged as a useful experimental platform to analyze biological samples in a high-throughput format. Different signal detection methods have been described to generate a quantitative readout on RPPA including the use of fluorescently labeled antibodies. Increasing the sensitivity of RPPA approaches is important since many signaling proteins or posttranslational modifications are present at a low level. Results A new antibody-mediated signal amplification (AMSA) strategy relying on sequential incubation steps with fluorescently-labeled secondary antibodies reactive against each other is introduced here. The signal quantification is performed in the near-infrared range. The RPPA-based analysis of 14 endogenous proteins in seven different cell lines demonstrated a strong correlation (r = 0.89) between AMSA and standard NIR detection. Probing serial dilutions of human cancer cell lines with different primary antibodies demonstrated that the new amplification approach improved the limit of detection especially for low abundant target proteins. Conclusions Antibody-mediated signal amplification is a convenient and cost-effective approach for the robust and specific quantification of low abundant proteins on RPPAs. Contrasting other amplification approaches it allows target protein detection over a large linear range. PMID:20569466

Experimentally induced central sensitization in the cervical spine evokes postural stiffening strategies in healthy young adults.

PubMed

Huntley, Andrew H; Srbely, John Z; Zettel, John L

2015-02-01

Dysequilibrium of cervicogenic origin can result from pain and injury to cervical paraspinal tissues post-whiplash; however, the specific physiological mechanisms still remain unclear. Central sensitization is a neuradaptive process which has been clinically associated with conditions of chronic pain and hypersensitivity. Strong links have been demonstrated between pain hypersensitivity and postural deficits post-whiplash; however, the precise mechanisms are still poorly understood. The purpose of this study was to explore the mechanisms of cervicogenic disequilibrium by investigating the effect of experimentally induced central sensitization in the cervical spine on postural stability in young healthy adults. Sixteen healthy young adults (7 males (22.6±1.13 years) and 9 females (22±2.69 years)) performed 30-s full-tandem stance trials on an AMTI force plate under normal and centrally sensitized conditions. The primary outcome variables included the standard deviation of the center of pressure (COP) position in medio-lateral (M-L) and antero-posterior (A-P) directions; sway range of the COP in M-L and A-P directions and the mean power frequency (MPF) of the COP and horizontal ground shear forces. Variability and sway range of the COP decreased with experimental induction of central sensitization, accompanied by an increase in MPF of COP displacement in both M-L and A-P directions, suggesting an increase in postural stiffening post-sensitization versus non-sensitized controls. Future studies need to further explore this relationship in clinical (whiplash, chronic pain) populations. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensitivity enhanced strain and temperature measurements based on FBG and frequency chirp magnification.

PubMed

Du, Jiangbing; He, Zuyuan

2013-11-04

In this work, highly sensitive measurements of strain and temperature have been demonstrated using a fiber Bragg grating (FBG) sensor with significantly enhance sensitivity by all-optical signal processing. The sensitivity enhancement is achieved by degenerated Four Wave Mixing (FWM) for frequency chirp magnification (FCM), which can be used for magnifying the wavelength drift of the FBG sensor induced by strain and temperature change. Highly sensitive measurements of static strain and temperature have been experimentally demonstrated with strain sensitivity of 5.36 pm/με and temperature sensitivity of 54.09 pm/°C. The sensitivity has been enhanced by a factor of five based on a 4-order FWM in a highly nonlinear fiber (HNLF).

Improved utilization of photogenerated charge using fluorine-doped TiO(2) hollow spheres scattering layer in dye-sensitized solar cells.

PubMed

Song, Junling; Yang, Hong Bin; Wang, Xiu; Khoo, Si Yun; Wong, C C; Liu, Xue-Wei; Li, Chang Ming

2012-07-25

We demonstrate a strategy to improve utilization of photogenerated charge in dye-sensitized solar cells (DSSCs) with fluorine-doped TiO2 hollow spheres as the scattering layer, which improves the fill factor from 69.4% to 74.1% and in turn results in an overall efficiency of photoanode increased by 13% (from 5.62% to 6.31%) in comparison with the control device using undoped TiO2 hollow spheres. It is proposed that the fluorine-doping improves the charge transfer and inhibition of charge recombination to enhance the utilization of the photogenerated charge in the photoanode.

A low-power, high-sensitivity micromachined optical magnetometer

NASA Astrophysics Data System (ADS)

Mhaskar, R.; Knappe, S.; Kitching, J.

2012-12-01

We demonstrate an optical magnetometer based on a microfabricated 87Rb vapor cell in a micromachined silicon sensor head. The alkali atom density in the vapor cell is increased by heating the cell with light brought to the sensor through an optical fiber, and absorbed by colored filters attached to the cell windows. A second fiber-optically coupled beam optically pumps and interrogates the atoms. The magnetometer operates on 140 mW of heating power and achieves a sensitivity below 20 fT/√Hz throughout most of the frequency band from 15 Hz to 100 Hz. Such a sensor can measure magnetic fields from the human heart and brain.

Opiate receptor binding in the brain of the seizure sensitive Mongolian gerbil (Meriones unguiculatus).

PubMed

Lee, R J; Olsen, R W; Lomax, P; McCabe, R T; Wamsley, J K

1984-12-01

Opiate receptor binding was studied in seizure sensitive (SS) and seizure resistant (SR) strains of the Mongolian gerbil. Cryostat sections of the brain were labeled with [3H]-dihydromorphine, subjected to autoradiography and analysed by microdensitometry. SS gerbils, prior to seizure induction, demonstrated overall greater brain opiate binding when compared to SR animals. Immediately following a seizure, binding in the interpeduncular nucleus fell to levels found in SR animals. The increased opiate binding in the SS (pre-seizure) compared to SR gerbils could reflect a deficit of endogenous ligand which could underlie the seizure diathesis in the gerbil.

The Rewarding and Locomotor-Sensitizing Effects of Repeated Cocaine Administration are Distinct and Separable in Mice

PubMed Central

Riday, Thorfinn T.; Kosofsky, Barry E.; Malanga, C.J.

2011-01-01

Repeated psychostimulant exposure progressively increases their potency to stimulate motor activity in rodents. This behavioral or locomotor sensitization is considered a model for some aspects of drug addiction in humans, particularly drug craving during abstinence. However, the role of increased motor behavior in drug reward remains incompletely understood. Intracranial self-stimulation (ICSS) was measured concurrently with locomotor activity to determine if acute intermittent cocaine administration had distinguishable effects on motor behavior and perception of brain stimulation-reward (BSR) in the same mice. Sensitization is associated with changes in neuronal activity and glutamatergic neurotransmission in brain reward circuitry. Expression of AMPA receptor subunits (GluR1 and GluR2) and CRE binding protein (CREB) was measured in the ventral tegmental area (VTA), dorsolateral striatum (STR) and nucleus accumbens (NAc) before and after a sensitizing regimen of cocaine, with and without ICSS. Repeated cocaine administration sensitized mice to its locomotor stimulating effects but not its ability to potentiate BSR. ICSS increased GluR1 in the VTA but not NAc or STR, demonstrating selective changes in protein expression with electrical stimulation of discrete brain structures. Repeated cocaine reduced GluR1, GluR2 and CREB expression in the NAc, and reductions of GluR1 and GluR2 but not CREB were further enhanced by ICSS. These data suggest that the effects of repeated cocaine exposure on reward and motor processes are dissociable in mice, and that reduction of excitatory neurotransmission in the NAc may predict altered motor function independently from changes in reward perception. PMID:22197517

Extinction of Zika virus and Usutu virus by lethal mutagenesis reveals different patterns of sensitivity to three mutagenic drugs.

PubMed

Bassi, Maria Rosaria; Sempere, Raquel Navarro; Meyn, Prashansa; Polacek, Charlotta; Arias, Armando

2018-06-18

Flaviviruses constitute an increasing source of public health concern with growing numbers of pathogens causing disease, and a geographic spread to temperate climates. Despite a large body of evidence supporting mutagenesis as a conceivable antiviral strategy, there is currently no data on the sensitivity to increased mutagenesis for Zika virus (ZIKV) and Usutu virus (USUV), two emerging flaviviral threats. In this study, we demonstrate that both viruses are sensitive to three ribonucleosides that have shown mutagenic activity against other RNA viruses - favipiravir, ribavirin and 5-fluorouracil - while they remain unaffected by a mutagenic deoxyribonucleoside. Serial cell culture passages of ZIKV in the presence of these compounds resulted in the rapid extinction of infectivity, suggesting elevated sensitivity to mutagenesis. USUV extinction was achieved when a 10-fold dilution was applied between every passage, but not in experiments involving undiluted virus, indicating an overall lower susceptibility than ZIKV. Although both viruses are inhibited by the same three drugs, ZIKV is relatively more susceptive to serial passage in the presence of purine analogues (favipiravir and ribavirin) while USUV replication is suppressed more efficiently by 5-fluorouracil. These differences in sensitivity typically correlate with the increases in the mutation frequencies observed in each nucleoside treatment. These results are relevant to the development of efficient therapies based on lethal mutagenesis, and support the rational selection of different mutagenic nucleosides for each pathogen. We will discuss the implications of these results to the fidelity of flavivirus replication, and the design of antiviral therapies based on lethal mutagenesis. Copyright © 2018 Bassi et al.

Sensitivity analysis of a model of CO2 exchange in tundra ecosystems by the adjoint method

NASA Technical Reports Server (NTRS)

Waelbroek, C.; Louis, J.-F.

1995-01-01

A model of net primary production (NPP), decomposition, and nitrogen cycling in tundra ecosystems has been developed. The adjoint technique is used to study the sensitivity of the computed annual net CO2 flux to perturbation in initial conditions, climatic inputs, and model's main parameters describing current seasonal CO2 exchange in wet sedge tundra at Barrow, Alaska. The results show that net CO2 flux is most sensitive to parameters characterizing litter chemical composition and more sensitive to decomposition parameters than to NPP parameters. This underlines the fact that in nutrient-limited ecosystems, decomposition drives net CO2 exchange by controlling mineralization of main nutrients. The results also indicate that the short-term (1 year) response of wet sedge tundra to CO2-induced warming is a significant increase in CO2 emission, creating a positive feedback to atmosphreic CO2 accumulation. However, a cloudiness increase during the same year can severely alter this response and lead to either a slight decrease or a strong increase in emitted CO2, depending on its exact timing. These results demonstrate that the adjoint method is well suited to study systems encountering regime changes, as a single run of the adjoint model provides sensitivities of the net CO2 flux to perturbations in all parameters and variables at any time of the year. Moreover, it is shown that large errors due to the presence of thresholds can be avoided by first delimiting the range of applicability of the adjoint results.

Fast computation of derivative based sensitivities of PSHA models via algorithmic differentiation

NASA Astrophysics Data System (ADS)

Leövey, Hernan; Molkenthin, Christian; Scherbaum, Frank; Griewank, Andreas; Kuehn, Nicolas; Stafford, Peter

2015-04-01

Probabilistic seismic hazard analysis (PSHA) is the preferred tool for estimation of potential ground-shaking hazard due to future earthquakes at a site of interest. A modern PSHA represents a complex framework which combines different models with possible many inputs. Sensitivity analysis is a valuable tool for quantifying changes of a model output as inputs are perturbed, identifying critical input parameters and obtaining insight in the model behavior. Differential sensitivity analysis relies on calculating first-order partial derivatives of the model output with respect to its inputs. Moreover, derivative based global sensitivity measures (Sobol' & Kucherenko '09) can be practically used to detect non-essential inputs of the models, thus restricting the focus of attention to a possible much smaller set of inputs. Nevertheless, obtaining first-order partial derivatives of complex models with traditional approaches can be very challenging, and usually increases the computation complexity linearly with the number of inputs appearing in the models. In this study we show how Algorithmic Differentiation (AD) tools can be used in a complex framework such as PSHA to successfully estimate derivative based sensitivities, as is the case in various other domains such as meteorology or aerodynamics, without no significant increase in the computation complexity required for the original computations. First we demonstrate the feasibility of the AD methodology by comparing AD derived sensitivities to analytically derived sensitivities for a basic case of PSHA using a simple ground-motion prediction equation. In a second step, we derive sensitivities via AD for a more complex PSHA study using a ground motion attenuation relation based on a stochastic method to simulate strong motion. The presented approach is general enough to accommodate more advanced PSHA studies of higher complexity.

Extension of the ADjoint Approach to a Laminar Navier-Stokes Solver

NASA Astrophysics Data System (ADS)

Paige, Cody

The use of adjoint methods is common in computational fluid dynamics to reduce the cost of the sensitivity analysis in an optimization cycle. The forward mode ADjoint is a combination of an adjoint sensitivity analysis method with a forward mode automatic differentiation (AD) and is a modification of the reverse mode ADjoint method proposed by Mader et al.[1]. A colouring acceleration technique is presented to reduce the computational cost increase associated with forward mode AD. The forward mode AD facilitates the implementation of the laminar Navier-Stokes (NS) equations. The forward mode ADjoint method is applied to a three-dimensional computational fluid dynamics solver. The resulting Euler and viscous ADjoint sensitivities are compared to the reverse mode Euler ADjoint derivatives and a complex-step method to demonstrate the reduced computational cost and accuracy. Both comparisons demonstrate the benefits of the colouring method and the practicality of using a forward mode AD. [1] Mader, C.A., Martins, J.R.R.A., Alonso, J.J., and van der Weide, E. (2008) ADjoint: An approach for the rapid development of discrete adjoint solvers. AIAA Journal, 46(4):863-873. doi:10.2514/1.29123.

SIG-VISA: Signal-based Vertically Integrated Seismic Monitoring

NASA Astrophysics Data System (ADS)

Moore, D.; Mayeda, K. M.; Myers, S. C.; Russell, S.

2013-12-01

Traditional seismic monitoring systems rely on discrete detections produced by station processing software; however, while such detections may constitute a useful summary of station activity, they discard large amounts of information present in the original recorded signal. We present SIG-VISA (Signal-based Vertically Integrated Seismic Analysis), a system for seismic monitoring through Bayesian inference on seismic signals. By directly modeling the recorded signal, our approach incorporates additional information unavailable to detection-based methods, enabling higher sensitivity and more accurate localization using techniques such as waveform matching. SIG-VISA's Bayesian forward model of seismic signal envelopes includes physically-derived models of travel times and source characteristics as well as Gaussian process (kriging) statistical models of signal properties that combine interpolation of historical data with extrapolation of learned physical trends. Applying Bayesian inference, we evaluate the model on earthquakes as well as the 2009 DPRK test event, demonstrating a waveform matching effect as part of the probabilistic inference, along with results on event localization and sensitivity. In particular, we demonstrate increased sensitivity from signal-based modeling, in which the SIGVISA signal model finds statistical evidence for arrivals even at stations for which the IMS station processing failed to register any detection.

Models of the electrically stimulated binaural system: A review.

PubMed

Dietz, Mathias

2016-01-01

In an increasing number of countries, the standard treatment for deaf individuals is moving toward the implantation of two cochlear implants. Today's device technology and fitting procedure, however, appears as if the two implants would serve two independent ears and brains. Many experimental studies have demonstrated that after careful matching and balancing of left and right stimulation in controlled laboratory studies most patients have almost normal sensitivity to interaural level differences and some sensitivity to interaural time differences (ITDs). Mechanisms underlying the limited ITD sensitivity are still poorly understood and many different aspects may contribute. Recent pioneering computational approaches identified some of the functional implications the electric input imposes on the neural brainstem circuits. Simultaneously these studies have raised new questions and certainly demonstrated that further refinement of the model stages is necessary. They join the experimental study's conclusions that binaural device technology, binaural fitting, specific speech coding strategies, and binaural signal processing algorithms are obviously missing components to maximize the benefit of bilateral implantation. Within this review, the existing models of the electrically stimulated binaural system are explained, compared, and discussed from a viewpoint of a "CI device with auditory system" and from that of neurophysiological research.

Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat.

PubMed

Kent, Tiffany L; Glybina, Inna V; Abrams, Gary W; Iezzi, Raymond

2008-01-01

To determine whether the sustained intravitreous delivery of CNTF modulates cortical response thresholds to electrical retinal stimulation in the RCS rat model of retinal degeneration. Animals were assigned to four groups: untreated, nonsurgical control and infusion groups of 10 ng/d CNTF, 1 ng/d CNTF, and PBS vehicle control. Thresholds for electrically evoked cortical potentials (EECPs) were recorded in response to transcorneal electrical stimulation of the retina at p30 and again at p60, after a three-week infusion. As the retina degenerated over time, EECP thresholds in response to electrical retinal stimulation increased. Eyes treated with 10 ng/d CNTF demonstrated significantly greater retinal sensitivity to electrical stimulation when compared with all other groups. In addition, eyes treated with 1 ng/d CNTF demonstrated significantly greater retinal sensitivity than both PBS-treated and untreated control groups. Retinal sensitivity to electrical stimulation was preserved in animals treated with chronic intravitreous infusion of CNTF. These data suggest that CNTF-mediated retinal neuroprotection may be a novel therapy that can lower stimulus thresholds in patients about to undergo retinal prosthesis implantation. Furthermore, it may maintain the long-term efficacy of these devices in patients.

Methamphetamine-sensitized rats show augmented dopamine release to methylphenidate stimulation: a positron emission tomography using [18F]fallypride.

PubMed

Ota, Miho; Ogawa, Shintaro; Kato, Koichi; Wakabayashi, Chisato; Kunugi, Hiroshi

2015-04-30

Previous studies demonstrated that patients with schizophrenia show greater sensitivity to psychostimulants than healthy subjects. Sensitization to psychostimulants and resultant alteration of dopaminergic neurotransmission in rodents have been suggested as a useful model of schizophrenia. This study was aimed to examine the use of methylphenidate as a psychostimulant to induce dopamine release and that of [18F]fallypride as a radioligand to estimate the release in a rat model of schizophrenia. Six rats were scanned by positron emission tomography (PET) twice before and after methylphenidate challenge to evaluate dopamine release. After the scans, these rats were sensitized by using repeated methamphetamine (MAP) administration. Then, they were re-scanned twice again before and after methylphenidate challenge to evaluate whether MAP-sensitized rats show greater sensitivity to methylphenidate. We revealed a main effect of MAP-pretreatment and that of metylphenidate challenge. We found that % change of distribution volume ratio after repeated administration of MAP was greater than that before sensitization. These results suggest that methylphenidate-induced striatal dopamine release increased after sensitization to MAP. PET scan using [18F]fallypride at methylphenidate-challenge may provide a biological marker for schizophrenia and be useful to diagnose schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia.

PubMed

Ohayon, Delphine; De Chiara, Alessia; Chapuis, Nicolas; Candalh, Céline; Mocek, Julie; Ribeil, Jean-Antoine; Haddaoui, Lamya; Ifrah, Norbert; Hermine, Olivier; Bouillaud, Frédéric; Frachet, Philippe; Bouscary, Didier; Witko-Sarsat, Véronique

2016-10-19

Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S). By interacting with nicotinamide phosphoribosyltransferase (NAMPT), a protein involved in NAD biosynthesis, PCNA coordinates glycolysis and survival, especially in HL-60R cells. These cells showed a dramatic increase in intracellular NAD+ concentration as well as glycolysis including increased expression and activity of hexokinase 1 and increased lactate production. Furthermore, this functional activity of cytoplasmic PCNA was also demonstrated in patients with acute myeloid leukemia (AML). Our data uncover a novel pathway of nuclear export of PCNA that drives cell survival by increasing metabolism flux.

Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia

PubMed Central

Ohayon, Delphine; De Chiara, Alessia; Chapuis, Nicolas; Candalh, Céline; Mocek, Julie; Ribeil, Jean-Antoine; Haddaoui, Lamya; Ifrah, Norbert; Hermine, Olivier; Bouillaud, Frédéric; Frachet, Philippe; Bouscary, Didier; Witko-Sarsat, Véronique

2016-01-01

Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S). By interacting with nicotinamide phosphoribosyltransferase (NAMPT), a protein involved in NAD biosynthesis, PCNA coordinates glycolysis and survival, especially in HL-60R cells. These cells showed a dramatic increase in intracellular NAD+ concentration as well as glycolysis including increased expression and activity of hexokinase 1 and increased lactate production. Furthermore, this functional activity of cytoplasmic PCNA was also demonstrated in patients with acute myeloid leukemia (AML). Our data uncover a novel pathway of nuclear export of PCNA that drives cell survival by increasing metabolism flux. PMID:27759041

Nocturnal snoring decreases daytime baroreceptor sensitivity.

PubMed

Schöbel, Christoph; Fietze, Ingo; Glos, Martin; Schary, Inett; Blau, Alexander; Baumann, Gert; Penzel, Thomas

2014-07-01

In patients with obstructive sleep apnea heart rate variability and baroreceptor sensitivity during night and daytime are impaired. Snoring without obstructive sleep apnea may already influence heart rate variability and baroreceptor sensitivity during daytime. Cardiovascular daytime testing was performed in 11 snorers and age, BMI, and gender matched controls. Sleep apnea and snoring were quantified by sleep recordings. Paced breathing was performed during daytime with ECG, non-invasive blood pressure, and respiration recorded. Heart rate variability and blood pressure variability were analyzed in the time and frequency domain. Baroreceptor sensitivity (alpha gain) was calculated. In snorers a significant increase in high frequency systolic blood pressure variability (SBPV-HF) compared to control group (0.37 mm Hg(2) vs. 0.11 mm Hg(2) for 12 breaths and 0.35 mm Hg(2) vs. 0.10 mm Hg(2) for 15 breaths) was demonstrated. Furthermore a lower baroreceptor sensitivity was found in snorers compared to controls (9.2 ms/mm Hg vs. 16.2 ms/mm Hg for 12 breaths and 8.5 ms/mm Hg vs. 17.4 ms/mm Hg for 15 breaths per minute) using the paced breathing protocol. Mean heart rate was elevated in snorers as well. Snorers may have a reduced parasympathetic tone during daytime rather than an increased sympathetic tone. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sampled-Data Techniques Applied to a Digital Controller for an Altitude Autopilot

NASA Technical Reports Server (NTRS)

Schmidt, Stanley F.; Harper, Eleanor V.

1959-01-01

Sampled-data theory, using the Z transformation, is applied to the design of a digital controller for an aircraft-altitude autopilot. Particular attention is focused on the sensitivity of the design to parameter variations and the abruptness of the response, that is, the normal acceleration required to carry out a transient maneuver. Consideration of these two characteristics of the system has shown that the finite settling time design method produces an unacceptable system, primarily because of the high sensitivity of the response to parameter variations, although abruptness can be controlled by increasing the sampling period. Also demonstrated is the importance of having well-damped poles or zeros if cancellation is attempted in the design methods. A different method of smoothing the response and obtaining a design which is not excessively sensitive is proposed, and examples are carried through to demonstrate the validity of the procedure. This method is based on design concepts of continuous systems, and it is shown that if no pole-zero cancellations are allowed in the design, one can obtain a response which is not too abrupt, is relatively insensitive to parameter variations, and is not sensitive to practical limits on control-surface rate. This particular design also has the simplest possible pulse transfer function for the digital controller. Simulation techniques and root loci are used for the verification of the design philosophy.

Silencing the Girdin gene enhances radio-sensitivity of hepatocellular carcinoma via suppression of glycolytic metabolism.

PubMed

Yu, Li; Sun, Yifan; Li, Jingjing; Wang, Yan; Zhu, Yuxing; Shi, Yong; Fan, Xiaojun; Zhou, Jianda; Bao, Ying; Xiao, Jie; Cao, Ke; Cao, Peiguo

2017-08-15

Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the radio-sensitivity of hepatocellular carcinoma remains unclear. A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression. Then, cell proliferation, colony formation, flow cytometric, scratch, and transwell assays were to examine the influence of Girdin silencing on cellular radiosensitivity. Glycolysis assays were conducted to exam cell glycolysis process. Western blotting was performed to explore the signaling pathway downstream of Girdin. Finally, animal experiments were performed to demonstrate the effect of CCDC88A silencing on the radiosensitivity of hepatoma in vivo. shRNA-induced Girdin silencing suppressed glycolysis and enhanced the radio-sensitivity of hepatic cell lines, HepG2 and Huh-7. Furthermore, silencing of Girdin inhibited the PI3K/AKT/HIF-1α signaling pathway, which is a central regulator of glycolysis. Girdin can regulate glycolysis in hepatocellular carcinoma cells through the PI3K/AKT/HIF-1α signaling pathway, which decreases the sensitivity of tumor cells to radiotherapy.

The evaluation and validation of Phadebas® paper as a presumptive screening tool for saliva on forensic exhibits.

PubMed

Wornes, Danielle J; Speers, Samuel J; Murakami, Julie A

2018-07-01

The Phadebas ® Forensic Press Test is routinely used for the detection of saliva. However, assessment of the use of Phadebas ® paper for this purpose has not been studied extensively. The suitability of Phadebas ® paper as a presumptive screening tool for saliva on forensic exhibits, was investigated by analysing the following: (1) sensitivity, (2) specificity, (3) effects of temperature on sensitivity and specificity, (4) detection of saliva in mixed body fluid samples, and (5) influence of substrate porosity. The results of this study demonstrated that Phadebas ® paper is more sensitive to α-amylase activity and less specific for saliva than previously reported. The use of an examination temperature of 37°C had no effect on sensitivity, but increased the incidence of cross-reactivity with other forensically relevant body fluid stains. Blood, urine and vaginal secretions can inhibit the detection of α-amylase activity with Phadebas ® paper in mixed stains of saliva and body fluid. Substrate porosity is a weak predictor for the time taken for a saliva stain to achieve a strong positive result on Phadebas ® paper. Overall, this study demonstrated that the Phadebas ® Forensic Press Test has limitations as a presumptive test for the accurate identification of saliva. Copyright © 2018 Elsevier B.V. All rights reserved.

Sensitivity to Sunburn Is Associated with Susceptibility to Ultraviolet Radiation–Induced Suppression of Cutaneous Cell–Mediated Immunity

PubMed Central

Kelly, Deirdre A.; Young, Antony R.; McGregor, Jane M.; Seed, Paul T.; Potten, Christopher S.; Walker, Susan L.

2000-01-01

Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P < 0.001), and a moderate sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer. PMID:10662801

ENSO Predictions in an Intermediate Coupled Model Influenced by Removing Initial Condition Errors in Sensitive Areas: A Target Observation Perspective

NASA Astrophysics Data System (ADS)

Tao, Ling-Jiang; Gao, Chuan; Zhang, Rong-Hua

2018-07-01

Previous studies indicate that ENSO predictions are particularly sensitive to the initial conditions in some key areas (socalled "sensitive areas"). And yet, few studies have quantified improvements in prediction skill in the context of an optimal observing system. In this study, the impact on prediction skill is explored using an intermediate coupled model in which errors in initial conditions formed to make ENSO predictions are removed in certain areas. Based on ideal observing system simulation experiments, the importance of various observational networks on improvement of El Niño prediction skill is examined. The results indicate that the initial states in the central and eastern equatorial Pacific are important to improve El Ni˜no prediction skill effectively. When removing the initial condition errors in the central equatorial Pacific, ENSO prediction errors can be reduced by 25%. Furthermore, combinations of various subregions are considered to demonstrate the efficiency on ENSO prediction skill. Particularly, seasonally varying observational networks are suggested to improve the prediction skill more effectively. For example, in addition to observing in the central equatorial Pacific and its north throughout the year, increasing observations in the eastern equatorial Pacific during April to October is crucially important, which can improve the prediction accuracy by 62%. These results also demonstrate the effectiveness of the conditional nonlinear optimal perturbation approach on detecting sensitive areas for target observations.

Selectively bred crossed high-alcohol-preferring mice drink to intoxication and develop functional tolerance, but not locomotor sensitization during free-choice ethanol access.

PubMed

Matson, Liana M; Kasten, Chelsea R; Boehm, Stephen L; Grahame, Nicholas J

2014-01-01

Crossed high-alcohol-preferring (cHAP) mice were selectively bred from a cross of the HAP1 × HAP2 replicate lines and demonstrate blood ethanol concentrations (BECs) during free-choice drinking reminiscent of those observed in alcohol-dependent humans. In this report, we investigated the relationship between free-choice drinking, intoxication, tolerance, and sensitization in cHAP mice. We hypothesized that initially mice would become ataxic after drinking alcohol, but that increased drinking over days would be accompanied by increasing tolerance to the ataxic effects of ethanol (EtOH). Male and female cHAP mice had free-choice access to 10% EtOH and water (E), while Water mice (W) had access to water alone. In experiment 1, the first drinking experience was monitored during the dark portion of the cycle. Once E mice reached an average intake rate of ≥1.5 g/kg/h, they, along with W mice, were tested for footslips on a balance beam, and BECs were assessed. In experiments 2, 3, and 4, after varying durations of free-choice 10% EtOH access (0, 3, 14, or 21 days), mice were challenged with 20% EtOH and tested for number of footslips on a balance beam or locomotor stimulant response. Blood was sampled for BEC determination. We found that cHAP mice rapidly acquire alcohol intakes that lead to ataxia. Over time, cHAP mice developed behavioral tolerance to the ataxic effects of alcohol, paralleled by escalating alcohol consumption. However, locomotor sensitization did not develop following 14 days of free-choice EtOH access. Overall, we observed increases in free-choice drinking with extended alcohol access paralleled by increases in functional tolerance, but not locomotor sensitization. These data support our hypothesis that escalating free-choice drinking over days in cHAP mice is driven by tolerance to alcohol's behavioral effects. These data are the first to demonstrate that escalating free-choice consumption is accompanied by increasing alcohol tolerance. In addition to buttressing the hypothesized importance of tolerance in drinking, our findings suggest that cHAP mice may be a unique, translational resource for studying tolerance as a contributor to and consequence of chronic, excessive EtOH consumption. Copyright © 2013 by the Research Society on Alcoholism.

Examining the latent structure of anxiety sensitivity in adolescents using factor mixture modeling.

PubMed

Allan, Nicholas P; MacPherson, Laura; Young, Kevin C; Lejuez, Carl W; Schmidt, Norman B

2014-09-01

Anxiety sensitivity has been implicated as an important risk factor, generalizable to most anxiety disorders. In adults, factor mixture modeling has been used to demonstrate that anxiety sensitivity is best conceptualized as categorical between individuals. That is, whereas most adults appear to possess normative levels of anxiety sensitivity, a small subset of the population appears to possess abnormally high levels of anxiety sensitivity. Further, those in the high anxiety sensitivity group are at increased risk of having high levels of anxiety and of having an anxiety disorder. This study was designed to determine whether these findings extend to adolescents. Factor mixture modeling was used to examine the best fitting model of anxiety sensitivity in a sample of 277 adolescents (M age = 11.0 years, SD = 0.81). Consistent with research in adults, the best fitting model consisted of 2 classes, 1 containing adolescents with high levels of anxiety sensitivity (n = 25) and another containing adolescents with normative levels of anxiety sensitivity (n = 252). Examination of anxiety sensitivity subscales revealed that the social concerns subscale was not important for classification of individuals. Convergent and discriminant validity of anxiety sensitivity classes were found in that membership in the high anxiety sensitivity class was associated with higher mean levels of anxiety symptoms, controlling for depression and externalizing problems, and was not associated with higher mean levels of depression or externalizing symptoms controlling for anxiety problems. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*

PubMed Central

Huo, Yuqing; Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Fan, Yang-Yi; Ong, Kuok Teong; Woo, Shih-Lung; Chapkin, Robert S.; Mashek, Douglas G.; Chen, Yanming; Dong, Hui; Lu, Fuer; Wei, Lai; Wu, Chaodong

2012-01-01

Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. PMID:22556414

Estradiol impairs the antiproliferative and proapoptotic effect of Zoledronic acid in hormone sensitive breast cancer cells in vitro

PubMed Central

Weingartshofer, Sigrid; Grunt, Thomas W.; Mairhofer, Mario; Tan, Yen; Gamper, Jutta; Singer, Christian F.

2017-01-01

Background Zoledronic acid (ZA) has antiresorptive effects and protects from bone metastasis in women with early breast cancer. In addition, in postmenopausal women with endocrine responsive breast cancer ZA prolongs DFS. The exact mechanism is still unclear. We have therefore investigated the effect of increasing concentrations of ZA in breast cancer cell lines in the absence or presence of estradiol to mimic the hormonal environment in vitro. Materials and methods Using assays for cell proliferation (EZ4U, BrdU) and cell death (Annexin/PI), we have analyzed the dose-dependent antiproliferative and pro-apoptotic effects of ZA in two hormone sensitive cell lines (MCF-7 and T47D) and a hormone insensitive, triple negative cell line (MDA-MB-231) in the presence of 0, 1 and 10 nM estradiol. Results In the absence of estradiol, ZA exerts dose-dependent antiproliferative and pro-apoptotic antitumor effects in both, hormone sensitive (MCF-7, T47D) and -insensitive (MDA-MB-231) breast cancer cell lines (p<0.0001). In the presence of estradiol, the antitumoral effect of ZA was significantly decreased only in the hormone sensitive MCF-7 and T47D cell lines (p = 0.0008 and p = 0.0008, respectively). Conclusion We have demonstrated that estradiol impairs the antiproliferative and proapoptotic effect of ZA in hormone sensitive, but not in hormone insensitive breast cancer cell lines. Our findings provide a possible explanation for the differential effect of ZA on DFS in pre- and postmenopausal patients with hormone sensitive early breast cancer, which has been demonstrated clinically. We further hypothesize that endocrine insensitive tumors such as triple negative breast cancer (TNBC) should benefit from ZA irrespective of their menopausal status. PMID:28945801

Estradiol impairs the antiproliferative and proapoptotic effect of Zoledronic acid in hormone sensitive breast cancer cells in vitro.

PubMed

Gschwantler-Kaulich, Daphne; Weingartshofer, Sigrid; Grunt, Thomas W; Mairhofer, Mario; Tan, Yen; Gamper, Jutta; Singer, Christian F

2017-01-01

Zoledronic acid (ZA) has antiresorptive effects and protects from bone metastasis in women with early breast cancer. In addition, in postmenopausal women with endocrine responsive breast cancer ZA prolongs DFS. The exact mechanism is still unclear. We have therefore investigated the effect of increasing concentrations of ZA in breast cancer cell lines in the absence or presence of estradiol to mimic the hormonal environment in vitro. Using assays for cell proliferation (EZ4U, BrdU) and cell death (Annexin/PI), we have analyzed the dose-dependent antiproliferative and pro-apoptotic effects of ZA in two hormone sensitive cell lines (MCF-7 and T47D) and a hormone insensitive, triple negative cell line (MDA-MB-231) in the presence of 0, 1 and 10 nM estradiol. In the absence of estradiol, ZA exerts dose-dependent antiproliferative and pro-apoptotic antitumor effects in both, hormone sensitive (MCF-7, T47D) and -insensitive (MDA-MB-231) breast cancer cell lines (p<0.0001). In the presence of estradiol, the antitumoral effect of ZA was significantly decreased only in the hormone sensitive MCF-7 and T47D cell lines (p = 0.0008 and p = 0.0008, respectively). We have demonstrated that estradiol impairs the antiproliferative and proapoptotic effect of ZA in hormone sensitive, but not in hormone insensitive breast cancer cell lines. Our findings provide a possible explanation for the differential effect of ZA on DFS in pre- and postmenopausal patients with hormone sensitive early breast cancer, which has been demonstrated clinically. We further hypothesize that endocrine insensitive tumors such as triple negative breast cancer (TNBC) should benefit from ZA irrespective of their menopausal status.

Impact of Breast Reader Assessment Strategy on mammographic radiologists' test reading performance.

PubMed

Suleiman, Wasfi I; Rawashdeh, Mohammad A; Lewis, Sarah J; McEntee, Mark F; Lee, Warwick; Tapia, Kriscia; Brennan, Patrick C

2016-06-01

The detection of breast cancer is somewhat limited by human factors, and thus there is a need to improve reader performance. This study assesses whether radiologists who regularly undertake the education in the form of the Breast Reader Assessment Strategy (BREAST) demonstrate any changes in mammography interpretation performance over time. In 2011, 2012 and 2013, 14 radiologists independently assessed a year-specific BREAST mammographic test-set. Radiologists read a different single test-set once each year, with each comprising 60 digital mammogram cases. Radiologists marked the location of suspected lesions without computer-aided diagnosis (CAD) and assigned a confidence rating of 2 for benign and 3-5 for malignant lesions. The mean sensitivity, specificity, location sensitivity, JAFROC FOM and ROC AUC were calculated. A Kruskal-Wallis test was used to compare the readings for the 14 radiologists across the 3 years. Wilcoxon signed rank test was used to assess comparison between pairs of years. Relationships between changes in performance and radiologist characteristics were examined using a Spearman's test. Significant increases were noted in mean sensitivity (P = 0.01), specificity (P = 0.01), location sensitivity (P = 0.001) and JAFROC FOM (P = 0.001) between 2011 and 2012. Between 2012 and 2013, significant improvements were noted in mean sensitivity (P = 0.003), specificity (P = 0.002), location sensitivity (P = 0.02), JAFROC FOM (P = 0.005) and ROC AUC (P = 0.008). No statistically significant correlations were shown between the levels of improvement and radiologists' characteristics. Radiologists' who undertake the BREAST programme demonstrate significant improvements in test-set performance during a 3-year period, highlighting the value of ongoing education through the use of test-set. © 2016 The Royal Australian and New Zealand College of Radiologists.

Locally placed nanoscale gold islands film within a TiO2 photoanode for enhanced plasmon light absorption in dye sensitized solar cells.

PubMed

Kim, Taeheon; Kumaresan, Yogeenth; Cho, Sung Jun; Lee, Chang-Lyoul; Lee, Heon; Jung, Gun Young

2016-01-01

As metal nanostructures demonstrated extraordinary plasmon resonance, their optical characteristics have widely been investigated in photo-electronic applications. However, there has been no clear demonstration on the location effect of plasmonic metal layer within the photoanode on both optical characteristics and photovoltaic performances. In this research, the gold (Au) nano-islands (NIs) film was embedded at different positions within the TiO 2 nanoparticulate photoanode in dye-sensitized solar cells (DSSC) to check the effect of plasmon resonance location on the device performance; at the top, in the middle, at the bottom of the TiO 2 photoanode, and also at all the three positions. The Au NIs were fabricated by annealing a Au thin film at 550 °C. The DSSC having the Au NIs-embedded TiO 2 photoanode exhibited an increase in short circuit currents (J sc ) and power conversion efficiency (PCE) owing to the plasmon resonance absorption. Thus, the PCE was increased from 5.92% (reference: only TiO 2 photoanode) to 6.52% when the Au NIs film was solely positioned at the bottom, in the middle or at the top of TiO 2 film. When the Au NIs films were placed at all the three positions, the J sc was increased by 16% compared to the reference cell, and consequently the PCE was further increased to 7.01%.

The Effect of an Increased Convective Entrainment Rate on Indian Monsoon Biases in the Met Office Unified Model

NASA Astrophysics Data System (ADS)

Bush, Stephanie; Turner, Andrew; Woolnough, Steve; Martin, Gill

2013-04-01

Global circulation models (GCMs) are a key tool for understanding and predicting monsoon rainfall, now and under future climate change. However, many GCMs show significant, systematic biases in their simulation of monsoon rainfall and dynamics that spin up over very short time scales and persist in the climate mean state. We describe several of these biases as simulated in the Met Office Unified Model and show they are sensitive to changes in the convective parameterization's entrainment rate. To improve our understanding of the biases and inform efforts to improve convective parameterizations, we explore the reasons for this sensitivity. We show the results of experiments where we increase the entrainment rate in regions of especially large bias: the western equatorial Indian Ocean, western north Pacific and India itself. We use the results to determine whether improvements in biases are due to the local increase in entrainment or are the remote response of the entrainment increase elsewhere in the GCM. We find that feedbacks usually strengthen the local response, but the local response leads to a different mean state change in different regions. We also show results from experiments which demonstrate the spin-up of the local response, which we use to further understand the response in complex regions such as the Western North Pacific. Our work demonstrates that local application of parameterization changes is a powerful tool for understanding their global impact.

New Amino-Acid-Based β-Phosphorylated Nitroxides for Probing Acidic pH in Biological Systems by EPR Spectroscopy.

PubMed

Thétiot-Laurent, Sophie; Gosset, Gaëlle; Clément, Jean-Louis; Cassien, Mathieu; Mercier, Anne; Siri, Didier; Gaudel-Siri, Anouk; Rockenbauer, Antal; Culcasi, Marcel; Pietri, Sylvia

2017-02-01

There is increasing interest in measuring pH in biological samples by using nitroxides with pH-dependent electron paramagnetic resonance (EPR) spectra. Aiming to improve the spectral sensitivity (Δa X ) of these probes (i.e., the difference between the EPR hyperfine splitting (hfs) in their protonated and unprotonated forms), we characterized a series of novel linear α-carboxy, α'-diethoxyphosphoryl nitroxides constructed on an amino acid core and featuring an (α or α')-C-H bond. In buffer, the three main hfs (a N , a H , and a P ) of their EPR spectra vary reversibly with pH and, from a P or a H titration curves, a two- to fourfold increase in sensitivity was achieved compared to reference imidazoline or imidazolidine nitroxides. The crystallized carboxylate 10 b (pK a ≈3.6), which demonstrated low cytotoxicity and good resistance to bioreduction, was applied to probe stomach acidity in rats. The results pave the way to a novel generation of highly sensitive EPR pH markers. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and in vitro antifungal efficacy of oleoyl-chitosan nanoparticles against plant pathogenic fungi.

PubMed

Xing, Ke; Shen, Xiaoqiang; Zhu, Xiao; Ju, Xiuyun; Miao, Xiangmin; Tian, Jun; Feng, Zhaozhong; Peng, Xue; Jiang, Jihong; Qin, Sheng

2016-01-01

An antifungal dispersion system was prepared by oleoyl-chitosan (O-chitosan) nanoparticles, and the antifungal activity against several plant pathogenic fungi was investigated. Under scanning electron microscopy, the nanoparticles formulation appeared to be uniform with almost spherical shape. The particle size of nanoparticles was around 296.962 nm. Transmission electron microscopy observation showed that nanoparticles could be well distributed in potato dextrose agar medium. Mycelium growth experiment demonstrated that Nigrospora sphaerica, Botryosphaeria dothidea, Nigrospora oryzae and Alternaria tenuissima were chitosan-sensitive, while Gibberella zeae and Fusarium culmorum were chitosan-resistant. The antifungal index was increased as the concentration of nanoparticles increased for chitosan-sensitive fungi. Fatty acid analyses revealed that plasma membranes of chitosan-sensitive fungi were shown to have lower levels of unsaturated fatty acid than chitosan-resistant fungi. Phylogenetic analysis based on ITS gene sequences indicated that two chitosan-resistant fungi had a near phylogenetic relationship. Results showed that O-chitosan nanoparticles could be a useful alternative for controlling pathogenic fungi in agriculture. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensitive assays enable detection of serum IgG antibodies against Clostridium difficile toxin A and toxin B in healthy subjects and patients with Clostridium difficile infection.

PubMed

Zhao, Xuemei; Bender, Florent; Shukla, Rajiv; Kang, John J; Caro-Aguilar, Ivette; Laterza, Omar F

2016-04-01

Pathogenic Clostridium difficile produces two proinflammatory exotoxins, toxin A and toxin B. Low level of serum antitoxin IgG antibodies is a risk factor for the development of primary and recurrent C. difficile infection (CDI). We developed and validated two sensitive, titer-based electrochemiluminescence assays for the detection of serum antibody levels against C. difficile toxins A and B. These assays demonstrated excellent precision. The sensitivity of the assays allowed the detection of antitoxin A and antitoxin B IgG antibodies in all tested serum samples during assay validation. The validated titer-based assays enable assessment of antitoxin A and antitoxin B IgG antibodies as potential biomarkers to identify patients with CDI at increased risk for CDI recurrence.

Increasing sensitivity and angle-of-view of mid-wave infrared detectors by integration with dielectric microspheres

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

Allen, Kenneth W., E-mail: kenneth.allen@gtri.gatech.edu; Astratov, Vasily N., E-mail: astratov@uncc.edu; Air Force Research Laboratory, Sensors Directorate, Wright Patterson AFB, Ohio 45433

2016-06-13

We observed up to 100 times enhancement of sensitivity of mid-wave infrared photodetectors in the 2–5 μm range by using photonic jets produced by sapphire, polystyrene, and soda-lime glass microspheres with diameters in the 90–300 μm range. By finite-difference time-domain (FDTD) method for modeling, we gain insight into the role of the microspheres refractive index, size, and alignment with respect to the detector mesa. A combination of enhanced sensitivity with angle-of-view (AOV) up to 20° is demonstrated for individual photodetectors. It is proposed that integration with microspheres can be scaled up for large focal plane arrays, which should provide maximal light collectionmore » efficiencies with wide AOVs, a combination of properties highly attractive for imaging applications.« less

Improving the performance of a pyramid wavefront sensor with modal sensitivity compensation.

PubMed

Korkiakoski, Visa; Vérinaud, Christophe; Le Louarn, Miska

2008-01-01

We describe a solution to increase the performance of a pyramid wavefront sensor (P-WFS) under bad seeing conditions. We show that most of the issues involve a reduced sensitivity that depends on the magnitude of the high frequency atmospheric distortions. We demonstrate in end-to-end closed loop adaptive optics simulations that with a modal sensitivity compensation method a high-order system with a nonmodulated P-WFS is robust in conditions with the Fried parameter r 0 at 0.5 microm in the range of 0.05-0.10 m. We also show that the method makes it possible to use a modal predictive control system to reach a total performance improvement of 0.06-0.45 in Strehl ratio at 1.6 microm. Especially at r 0=0.05 m the gain is dramatic.

High-sensitivity pressure sensor based on fiber Mach-Zehnder interferometer

NASA Astrophysics Data System (ADS)

Wu, Yue; Xu, Yao; Yang, Yuguang; Jin, Wenxing; Jiang, Youchao; Shen, Ya; Jian, Shuisheng

2017-10-01

In this paper we propose and experimentally demonstrate an optical fiber structure sensor based on a Mach-Zehnder interferometer for pressure measurement. The fiber sensor is composed of a single-mode-no-core-single-mode structure, a section of capillary pure silica tube and refractive index matching fluid (RIMF). As the pressure decreases, the sealed air in the tube expands and the liquid level of the RIMF increases, which causes a wavelength shift of the interferometer. The measurement of the pressure variation can thus be achieved by monitoring the wavelength shift. The experimental results agree well with the numerical simulation, and a maximum pressure sensitivity of 266.6 nm Mpa-1 is achieved experimentally. Furthermore, the proposed fiber sensor has the potential to obtain higher sensitivity by enlarging the length of the air cavity.

Highly Sensitive Bulk Silicon Chemical Sensors with Sub-5 nm Thin Charge Inversion Layers.

PubMed

Fahad, Hossain M; Gupta, Niharika; Han, Rui; Desai, Sujay B; Javey, Ali

2018-03-27

There is an increasing demand for mass-producible, low-power gas sensors in a wide variety of industrial and consumer applications. Here, we report chemical-sensitive field-effect-transistors (CS-FETs) based on bulk silicon wafers, wherein an electrostatically confined sub-5 nm thin charge inversion layer is modulated by chemical exposure to achieve a high-sensitivity gas-sensing platform. Using hydrogen sensing as a "litmus" test, we demonstrate large sensor responses (>1000%) to 0.5% H 2 gas, with fast response (<60 s) and recovery times (<120 s) at room temperature and low power (<50 μW). On the basis of these performance metrics as well as standardized benchmarking, we show that bulk silicon CS-FETs offer similar or better sensing performance compared to emerging nanostructures semiconductors while providing a highly scalable and manufacturable platform.

Development of Neural Sensitivity to Face Identity Correlates with Perceptual Discriminability.

PubMed

Natu, Vaidehi S; Barnett, Michael A; Hartley, Jake; Gomez, Jesse; Stigliani, Anthony; Grill-Spector, Kalanit

2016-10-19

Face perception is subserved by a series of face-selective regions in the human ventral stream, which undergo prolonged development from childhood to adulthood. However, it is unknown how neural development of these regions relates to the development of face-perception abilities. Here, we used functional magnetic resonance imaging (fMRI) to measure brain responses of ventral occipitotemporal regions in children (ages, 5-12 years) and adults (ages, 19-34 years) when they viewed faces that parametrically varied in dissimilarity. Since similar faces generate lower responses than dissimilar faces due to fMRI adaptation, this design objectively evaluates neural sensitivity to face identity across development. Additionally, a subset of subjects participated in a behavioral experiment to assess perceptual discriminability of face identity. Our data reveal three main findings: (1) neural sensitivity to face identity increases with age in face-selective but not object-selective regions; (2) the amplitude of responses to faces increases with age in both face-selective and object-selective regions; and (3) perceptual discriminability of face identity is correlated with the neural sensitivity to face identity of face-selective regions. In contrast, perceptual discriminability is not correlated with the amplitude of response in face-selective regions or of responses of object-selective regions. These data suggest that developmental increases in neural sensitivity to face identity in face-selective regions improve perceptual discriminability of faces. Our findings significantly advance the understanding of the neural mechanisms of development of face perception and open new avenues for using fMRI adaptation to study the neural development of high-level visual and cognitive functions more broadly. Face perception, which is critical for daily social interactions, develops from childhood to adulthood. However, it is unknown what developmental changes in the brain lead to improved performance. Using fMRI in children and adults, we find that from childhood to adulthood, neural sensitivity to changes in face identity increases in face-selective regions. Critically, subjects' perceptual discriminability among faces is linked to neural sensitivity: participants with higher neural sensitivity in face-selective regions demonstrate higher perceptual discriminability. Thus, our results suggest that developmental increases in face-selective regions' sensitivity to face identity improve perceptual discrimination of faces. These findings significantly advance understanding of the neural mechanisms underlying the development of face perception and have important implications for assessing both typical and atypical development. Copyright © 2016 the authors 0270-6474/16/3610893-15$15.00/0.

Insecticide toxicity to oriental fruit fly Bactrocera dorsalis (Diptera: Tephritidae) is influenced by environmental factors.

PubMed

Lin, Yuying; Jin, Tao; Zeng, Ling; Lu, Yongyue

2013-02-01

In this study, we investigated the effects of environmental factors (temperature, dose, dietary source, and feeding density) on the insecticide tolerance of Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). The results indicated that the toxicities of trichlorphon and abamectin to B. dorsalis increased with an increase in temperature. At 15-35 degrees C, the toxicity of beta-cypermethrin decreased with an increase in temperature at low doses (0.82 and 1.86 mg/L), but was similar at a high dose (4.18 mg/L). These results demonstrated that the temperature coefficient of beta-cypermethrin was related to both temperature and dosage. The insecticide sensitivity of B. dorsalis reared on different dietary sources was significantly different. Trichlorphon sensitivity of B. dorsalis fed on banana was the highest with an LC50 of 1.61 mg/L, followed by on apple, carambola, semiartificial diet, pear, mango, guava, orange, and papaya. With an increasing feeding density, the sensitivity of B. dorsalis adults to trichlorphon increased, while the sensitivities of B. dorsalis adults to abamectin and beta-cypermethrin decreased. The differences between LC50 values of insects reared at densities of 10 and 13 eggs/g of semiartificial diet to trichlorphon, abamectin and beta-cypermethrin were not significant. This result suggested that representative toxicity could be obtained by using adults developed at a feeding density between 10-13 eggs/g of semiartificial diet. Adult body weight was positively correlated with the LC50 value of trichlorphon, but was negatively correlated with the toxicities of abamectin and beta-cypermethrin. These results suggested that the effects of adult body weight on the toxicity of insecticides were different among different chemicals.

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

NASA Technical Reports Server (NTRS)

Jacob, G.; Shannon, J. R.; Costa, F.; Furlan, R.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.

1999-01-01

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

Sucrose and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: Role of BDNF and β-endorphin.

PubMed

Nuseir, Khawla Q; Alzoubi, Karem H; Alhusban, Ahmed; Bawaane, Areej; Al-Azzani, Mohammed; Khabour, Omar F

2017-10-01

Pain in neonates is associated with short and long-term adverse outcomes. Data demonstrated that long-term consequences of untreated pain are linked to the plasticity of the neonate's brain. Sucrose is effective and safe for reducing painful procedures from single events. However, the mechanism of sucrose-induced analgesia is not fully understood. The role of the opioid system in this analgesia using the opioid receptor antagonist Naltrexone was investigated, plus the long-term effects on learning and memory formation during adulthood. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution and/or naltrexone were administered before the pricks. All treatments started on day one of birth and continued for two weeks. At the end of 8weeks, behavioral studies were conducted to test spatial learning and memory using radial arm water maze (RAWM), and pain threshold via foot-withdrawal response to a hot plate. The hippocampus was dissected; levels of brain derived neurotrophic factor (BDNF) and endorphins were assessed using ELISA. Acute repetitive neonatal pain increased pain sensitivity later in life, while naltrexone with sucrose decreased pain sensitivity. Naltrexone and/or sucrose prevented neonatal pain induced impairment of long-term memory, while neonatal pain decreased levels of BDNF in the hippocampus; this decrease was averted by sucrose and naltrexone. Sucrose with naltrexone significantly increased β-endorphin levels in noxiously stimulated rats. In conclusion, naltrexone and sucrose can reverse increased pain sensitivity and impaired long-term memory induced by acute repetitive neonatal pain probably by normalizing BDNF expression and increasing β-endorphin levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.

PubMed

Guo, Tingqing; Jou, William; Chanturiya, Tatyana; Portas, Jennifer; Gavrilova, Oksana; McPherron, Alexandra C

2009-01-01

Myostatin (Mstn) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn(-/-) mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn(-/-) mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn(-/-) mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn(-/-) mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn(-/-) mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn(-/-) mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes.

Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high-fat feeding regardless of insulin-sensitizing treatment.

PubMed

Newsom, Sean A; Miller, Benjamin F; Hamilton, Karyn L; Ehrlicher, Sarah E; Stierwalt, Harrison D; Robinson, Matthew M

2017-11-01

Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial, with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle. Insulin resistance was induced in C57BL/6J mice using 4 wk of a high-fat compared with a low-fat diet. For 8 additional weeks, diets were enriched with pioglitazone to restore insulin sensitivity compared with nonenriched control low-fat or high-fat diets. Skeletal muscle mitochondrial protein synthesis was measured using deuterium oxide labeling during weeks 10-12 High-resolution respirometry was performed using palmitoyl-l-carnitine, glutamate+malate, and glutamate+malate+succinate as substrates for mitochondria isolated from quadriceps. Mitochondrial protein synthesis and palmitoyl- l-carnitine oxidation were increased in mice consuming a high-fat diet, regardless of differences in insulin sensitivity with pioglitazone treatment. There was no effect of diet or pioglitazone treatment on ADP-stimulated respiration or H 2 O 2 emission using glutamate+malate or glutamate+malate+succinate. The results demonstrate no impairments to mitochondrial protein synthesis or respiration following induction of insulin resistance. Instead, mitochondrial protein synthesis was increased with a high-fat diet and may contribute to remodeling of the mitochondria to increase lipid oxidation capacity. Mitochondrial adaptations with a high-fat diet appear driven by nutrient availability, not intrinsic defects that contribute to insulin resistance. Copyright © 2017 the American Physiological Society.

A Transient Dopamine Signal Represents Avoidance Value and Causally Influences the Demand to Avoid

PubMed Central

Pultorak, Katherine J.; Schelp, Scott A.; Isaacs, Dominic P.; Krzystyniak, Gregory

2018-01-01

Abstract While an extensive literature supports the notion that mesocorticolimbic dopamine plays a role in negative reinforcement, recent evidence suggests that dopamine exclusively encodes the value of positive reinforcement. In the present study, we employed a behavioral economics approach to investigate whether dopamine plays a role in the valuation of negative reinforcement. Using rats as subjects, we first applied fast-scan cyclic voltammetry (FSCV) to determine that dopamine concentration decreases with the number of lever presses required to avoid electrical footshock (i.e., the economic price of avoidance). Analysis of the rate of decay of avoidance demand curves, which depict an inverse relationship between avoidance and increasing price, allows for inference of the worth an animal places on avoidance outcomes. Rapidly decaying demand curves indicate increased price sensitivity, or low worth placed on avoidance outcomes, while slow rates of decay indicate reduced price sensitivity, or greater worth placed on avoidance outcomes. We therefore used optogenetics to assess how inducing dopamine release causally modifies the demand to avoid electrical footshock in an economic setting. Increasing release at an avoidance predictive cue made animals more sensitive to price, consistent with a negative reward prediction error (i.e., the animal perceives they received a worse outcome than expected). Increasing release at avoidance made animals less sensitive to price, consistent with a positive reward prediction error (i.e., the animal perceives they received a better outcome than expected). These data demonstrate that transient dopamine release events represent the value of avoidance outcomes and can predictably modify the demand to avoid. PMID:29766047

A novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China

PubMed Central

Yang, Yanzheng; Zhu, Qiuan; Peng, Changhui; Wang, Han; Xue, Wei; Lin, Guanghui; Wen, Zhongming; Chang, Jie; Wang, Meng; Liu, Guobin; Li, Shiqing

2016-01-01

Increasing evidence indicates that current dynamic global vegetation models (DGVMs) have suffered from insufficient realism and are difficult to improve, particularly because they are built on plant functional type (PFT) schemes. Therefore, new approaches, such as plant trait-based methods, are urgently needed to replace PFT schemes when predicting the distribution of vegetation and investigating vegetation sensitivity. As an important direction towards constructing next-generation DGVMs based on plant functional traits, we propose a novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China. The results demonstrated that a Gaussian mixture model (GMM) trained with a LMA-Nmass-LAI data combination yielded an accuracy of 72.82% in simulating vegetation distribution, providing more detailed parameter information regarding community structures and ecosystem functions. The new approach also performed well in analyses of vegetation sensitivity to different climatic scenarios. Although the trait-climate relationship is not the only candidate useful for predicting vegetation distributions and analysing climatic sensitivity, it sheds new light on the development of next-generation trait-based DGVMs. PMID:27052108

High-sensitivity bend angle measurements using optical fiber gratings.

PubMed

Rauf, Abdul; Zhao, Jianlin; Jiang, Biqiang

2013-07-20

We present a high-sensitivity and more flexible bend measurement method, which is based on the coupling of core mode to the cladding modes at the bending region in concatenation with optical fiber grating serving as band reflector. The characteristics of a bend sensing arm composed of bending region and optical fiber grating is examined for different configurations including single fiber Bragg grating (FBG), chirped FBG (CFBG), and double FBGs. The bend loss curves for coated, stripped, and etched sections of fiber in the bending region with FBG, CFBG, and double FBG are obtained experimentally. The effect of separation between bending region and optical fiber grating on loss is measured. The loss responses for single FBG and CFBG configurations are compared to discover the effectiveness for practical applications. It is demonstrated that the sensitivity of the double FBG scheme is twice that of the single FBG and CFBG configurations, and hence acts as sensitivity multiplier. The bend loss response for different fiber diameters obtained through etching in 40% hydrofluoric acid, is measured in double FBG scheme that resulted in a significant increase in the sensitivity, and reduction of dead-zone.

Mid-infrared refractive index sensing using optimized slotted photonic crystal waveguides

NASA Astrophysics Data System (ADS)

Kassa-Baghdouche, Lazhar; Cassan, Eric

2018-02-01

Slotted photonic crystal waveguides (SPCWs) were designed to act as refractive index sensing devices at mid-infrared (IR) wavelengths around λ = 3.6 μm. In particular, effort was made to engineer the input and output slot waveguide interfaces in order to increase the effective sensitivity through resonant tapering. A slotted PhC waveguide immersed in air and liquid cladding layers was considered. To determine the performance of the sensor, the sensitivity of the device was estimated by calculating the shift in the upper band edge of the output transmission spectrum. The results showed that the sensitivity of a conventionally designed SPCW followed by modifications in the structure parameter yielded a 510 nm shift in the wavelength position of the upper band edge, indicating a sensitivity of more than 1150 nm per refractive index unit (RIU) with an insertion loss level of -0.3 dB. This work demonstrates the viability of photonic crystal waveguide high sensitivity devices in the Mid-IR, following a transposition of the concepts inherited from the telecom band and an optimization of the design, in particular a minimization of photonic device insertion losses.

CASL L2 milestone report : VUQ.Y1.03, %22Enable statistical sensitivity and UQ demonstrations for VERA.%22

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

Sung, Yixing; Adams, Brian M.; Witkowski, Walter R.

2011-04-01

The CASL Level 2 Milestone VUQ.Y1.03, 'Enable statistical sensitivity and UQ demonstrations for VERA,' was successfully completed in March 2011. The VUQ focus area led this effort, in close partnership with AMA, and with support from VRI. DAKOTA was coupled to VIPRE-W thermal-hydraulics simulations representing reactors of interest to address crud-related challenge problems in order to understand the sensitivity and uncertainty in simulation outputs with respect to uncertain operating and model form parameters. This report summarizes work coupling the software tools, characterizing uncertainties, selecting sensitivity and uncertainty quantification algorithms, and analyzing the results of iterative studies. These demonstration studies focusedmore » on sensitivity and uncertainty of mass evaporation rate calculated by VIPRE-W, a key predictor for crud-induced power shift (CIPS).« less

Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury

PubMed Central

Pyzik, Michal; Rath, Timo; Kuo, Timothy T.; Win, Sanda; Baker, Kristi; Hubbard, Jonathan J.; Grenha, Rosa; Gandhi, Amit; Krämer, Thomas D.; Mezo, Adam R.; McDonnell, Kevin; Nienaber, Vicki; Andersen, Jan Terje; Mizoguchi, Atsushi; Blumberg, Laurence; Purohit, Shalaka; Jones, Susan D.; Christianson, Greg; Lencer, Wayne I.; Sandlie, Inger; Kaplowitz, Neil; Roopenian, Derry C.; Blumberg, Richard S.

2017-01-01

The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood. Here we demonstrate that mice with global or liver-specific FcRn deletion exhibit hypoalbuminemia, albumin loss into the bile, and increased albumin levels in the hepatocyte. In vitro models with polarized cells illustrate that FcRn mediates basal recycling and bidirectional transcytosis of albumin and uniquely determines the physiologic release of newly synthesized albumin into the basal milieu. These properties allow hepatic FcRn to mediate albumin delivery and maintenance in the circulation, but they also enhance sensitivity to the albumin-bound hepatotoxin, acetaminophen (APAP). As such, global or liver-specific deletion of FcRn results in resistance to APAP-induced liver injury through increased albumin loss into the bile and increased intracellular albumin scavenging of reactive oxygen species. Further, protection from injury is achieved by pharmacologic blockade of FcRn–albumin interactions with monoclonal antibodies or peptide mimetics, which cause hypoalbuminemia, biliary loss of albumin, and increased intracellular accumulation of albumin in the hepatocyte. Together, these studies demonstrate that the main function of hepatic FcRn is to direct albumin into the circulation, thereby also increasing hepatocyte sensitivity to toxicity. PMID:28330995

The Effect of Meal Frequency on the Fatty Acid Composition of Serum Phospholipids in Patients with Type 2 Diabetes.

PubMed

Kahleova, Hana; Malinska, Hana; Kazdova, Ludmila; Belinova, Lenka; Tura, Andrea; Hill, Martin; Pelikanova, Terezie

2016-01-01

Fatty acids are important cellular constituents that can affect many metabolic processes relevant for the development of diabetes and its complications. We previously demonstrated a positive effect of eating just 2 meals a day, breakfast and lunch, compared to 6 small meals. The aim of this secondary analysis was to explore the effect of meal frequency on the fatty acid composition of serum phospholipids in subjects with type 2 diabetes (T2D). In a randomized, crossover study, we assigned 54 patients with T2D to follow one of 2 regimens of a hypocaloric diet (-500 kcal/day), each for 12 weeks: 6 meals (A6) or 2 meals a day, breakfast and lunch (B2). The diet in both regimens had the same macronutrient and energy content. The fatty acid composition of serum phospholipids was measured at weeks 0, 12, and 24, using gas liquid chromatography. Insulin sensitivity was derived as an oral glucose insulin sensitivity (OGIS) index. Saturated fatty acids (mainly myristic and palmitic acids) decreased (p < 0.001) and n6 polyunsaturated fatty acids increased (p < 0.001) in response to both regimens but more with B2 (p < 0.001 for both). Monounsaturated fatty acids decreased (p < 0.05) and n3 polyunsaturated fatty acids increased (p < 0.001) in response to both regimens, with no difference between the regimens. An increase in OGIS correlated positively with changes in the proportion of linoleic acid in B2. This correlation remained significant even after adjustment for changes in body mass index (BMI; r = +0.38; p = 0.012). We demonstrated that meal frequency affects the fatty acid composition of serum phospholipids. The B2 regimen had more marked positive effects, with saturated fatty acids and the ratio of saturated to unsaturated fatty acids decreasing more. The increase in linoleic acid could partly explain the insulin-sensitizing effect of B2 in T2D.

Wnt5a Signaling Promotes Host Defense against Leishmania donovani Infection.

PubMed

Chakraborty, Arijit; Kurati, Sony Priya; Mahata, Sushil K; Sundar, Shyam; Roy, Syamal; Sen, Malini

2017-08-01

Leishmania donovani infects macrophages, disrupting immune homeostasis. The underlying mechanism that sustains infection remains unresolved. In view of the potential of Wnt5a signaling to support immune homeostasis, we evaluated the interrelationship of Wnt5a signaling and Leishmania donovani infection. Upon infecting macrophages separately with antimony drug-sensitive and -resistant L. donovani , we noted disruption in the steady-state level of Wnt5a. Moreover, inhibition of Wnt5a signaling by small interfering RNA transfection in vitro or by use of inhibitor of Wnt production in vivo led to an increase in cellular parasite load. In contrast, treatment of macrophages with recombinant Wnt5a caused a decrease in the load of antimony-sensitive and -resistant parasites, thus confirming that Wnt5a signaling antagonizes L. donovani infection. Using inhibitors of the Wnt5a signaling intermediates Rac1 and Rho kinase, we demonstrated that Wnt5a-mediated inhibition of parasite infection in macrophages is Rac1/Rho dependent. Furthermore, phalloidin staining and reactive oxygen species estimation of Wnt5a-treated macrophages suggested that a Wnt5a-Rac/Rho-mediated decrease in parasite load is associated with an increase in F- actin assembly and NADPH oxidase activity. Moreover, live microscopy of L. donovani -infected macrophages treated with Wnt5a demonstrated increased endosomal/lysosomal fusions with parasite-containing vacuoles (parasitophorous vacuoles [PV]). An increase in PV-endosomal/lysosomal fusion accompanied by augmented PV degradation in Wnt5a-treated macrophages was also apparent from transmission electron microscopy of infected cells. Our results suggest that, although L. donovani evades host immune response, at least in part through inhibition of Wnt5a signaling, revamping Wnt5a signaling can inhibit L. donovani infection, irrespective of drug sensitivity or resistance. Copyright © 2017 by The American Association of Immunologists, Inc.

Fluorescent sensing with Fresnel microlenses for optofluidic systems

NASA Astrophysics Data System (ADS)

Siudzińska, Anna; Miszczuk, Andrzej; Marczak, Jacek; Komorowska, Katarzyna

2017-05-01

The concept of fluorescent sensing in a microchannel equipped with focusing light Fresnel lenses has been demonstrated. The concept employs a line or array of Fresnel lenses generating a line or array of focused light spots within a microfluidic channel, to increase the sensitivity of fluorescent signal detection in the system. We have presented efficient methods of master mold fabrication based on the lithography method and focused ion beam milling. The flexible microchannel was fabricated by an imprint process with new thiolene-epoxy resin with a good ability to replicate even submicron-size features. For final imprinted lenses, the measured background to peak signal level shows more than nine times the increase in brightness at the center of the focal spot for the green part of the spectrum (532 nm). The effectiveness of the microlenses in fluorescent-marked Escherichia coli bacteria was confirmed in a basic fluoroscope experiment, showing the increase of the sensitivity of the detection by the order of magnitude.

Synthesis and Swelling Behavior of pH-Sensitive Semi-IPN Superabsorbent Hydrogels Based on Poly(acrylic acid) Reinforced with Cellulose Nanocrystals

PubMed Central

Lim, Lim Sze; Rosli, Noor Afizah; Ahmad, Ishak; Mat Lazim, Azwan; Mohd Amin, Mohd Cairul Iqbal

2017-01-01

pH-sensitive poly(acrylic acid) (PAA) hydrogel reinforced with cellulose nanocrystals (CNC) was prepared. Acrylic acid (AA) was subjected to chemical cross-linking using the cross-linking agent MBA (N,N-methylenebisacrylamide) with CNC entrapped in the PAA matrix. The quantity of CNC was varied between 0, 5, 10, 15, 20, and 25 wt %. X-ray diffraction (XRD) data showed an increase in crystallinity with the addition of CNC, while rheology tests demonstrated a significant increase in the storage modulus of the hydrogel with an increase in CNC content. It was found that the hydrogel reached maximum swelling at pH 7. The potential of the resulting hydrogels to act as drug carriers was then evaluated by means of the drug encapsulation efficiency test using theophylline as a model drug. It was observed that 15% CNC/PAA hydrogel showed the potential to be used as drug carrier system. PMID:29156613

Relationship between Trends in Land Precipitation and Tropical SST Gradient

NASA Technical Reports Server (NTRS)

Chung, Chul Eddy; Ramanathan, V.

2007-01-01

In this study, we examined global zonal/annual mean precipitation trends. Land precipitation trend from 1951 to 2002 shows widespread drying between 10 S to 20 N but the trend from 1977 to 2002 shows partial recovery. Based on general circulation model sensitivity studies, we suggested that these features are driven largely by the meridional SST gradient trend in the tropics. Our idealized CCM3 experiments substantiated that land precipitation is more sensitive to meridional SST gradient than to an overall tropical warming. Various simulations produced for the IPCC 4th assessment report demonstrate that increasing CO2 increases SST in the entire tropics non-uniformly and increases land precipitation only in certain latitude belts, again pointing to the importance of SST gradient change. Temporally varying aerosols in the IPCC simulations alter meridional SST gradient and land precipitation substantially. Anthropogenic aerosol direct solar forcing without its effects on SST is shown by the CCM3 to have weak but non-negligible influence on land precipitation.

Stiffness mapping prostate biopsy samples using a tactile sensor.

PubMed

Peng, Qiyu; Omata, Sadao; Peehl, Donna M; Constantinou, Chris E

2011-01-01

Previous studies have demonstrated that the stiffness of cancerous cells reflects their pathological stage and progression rates, with increased cancerous cell stiffness associated with increased aggressiveness. Therefore, the elasticity of the cancerous cells has the potential to be used as an indicator of the cancer's aggressiveness. However, the sensitivity and resolution of current palpation and imaging techniques are not sufficient to detect small cancerous tissues. In previous studies, we developed a tactile-based device to map with high resolution the stiffness of a tissue section. The purpose of this study is to evaluate this device using different tissues (BPH, Cancer and PZ) collected from human prostates. The preliminary results show that the tactile device is sensitive enough to tell the differences of the stiffness of different tissues. The results also disclosed the factors (humidity, temperature and tissue degradation) which could dramatically affect the results of stiffness mapping. The tactile technology described in this paper has the potential to help disclose the underlying mechanical mechanisms that lead to increased stiffness in prostate tumors.

Obesity, Insulin Resistance and Diabetes: Sex Differences and Role of Estrogen Receptors

PubMed Central

Meyer, Matthias R.; Clegg, Deborah J.; Prossnitz, Eric R.; Barton, Matthias

2010-01-01

Obesity increases the risk of coronary artery disease through insulin resistance, diabetes, arterial hypertension, and dyslipidemia. The prevalence of obesity has increased worldwide and is particularly high among middle-aged women and men. After menopause, women are at an increased risk to develop visceral obesity due to the loss of endogenous ovarian hormone production. Effects of estrogens are classically mediated by the two nuclear estrogen receptors (ERs) α and β. In addition, more recent research has shown that the intracellular transmembrane G protein-coupled estrogen receptor, GPER, originally designated as GPR30, also mediates some of the actions attributed to estrogens. Estrogen and its receptors are important regulators of body weight and insulin sensitivity not only in women, but also in men as demonstrated by ER mutations in rodents and humans. This article reviews the role of sex hormones and estrogen receptors in the context of obesity, insulin sensitivity and diabetes as well as the related clinical issues in females and males. PMID:21281456

Key Policy Makers' Awareness of Tobacco Taxation Effectiveness through a Sensitization Program.

PubMed

Heydari, Gholamreza; Ebn Ahmady, Arezoo; Lando, Harry A; Chamyani, Fahimeh; Masjedi, Mohammadreza; Shadmehr, Mohammad B; Fadaizadeh, Lida

2015-12-01

The implementation of 5 of the 6 WHO MPOWER program in Iran is satisfactory; the only notable shortcoming is the lack of tobacco taxation increases. This study was designed to increase key policy makers' awareness of tobacco taxation effectiveness through a sensitization program in Iran. This analytical and semi-experimental study in 2014 included 110 tobacco control key policy makers, who were trained and received educational materials on the importance of tobacco taxation. A valid and reliable questionnaire was completed before and three months after intervention. Data were analyzed using mean (SD), t-Test and analysis of variance. The mean (SD) scores at pre- and post-test were 2.7 ± 3 and 8.8 ± 1 out of 10, respectively. Paired t-tests demonstrated a significant difference in the pre- post-test knowledge scores. Increasing knowledge and promoting favorable attitudes of policy makers can lead to greater attention which could in turn change tobacco taxation policies.

Tuning pentacene based dye-sensitized solar cells.

PubMed

Kunzmann, Andreas; Gruber, Marco; Casillas, Rubén; Tykwinski, Rik R; Costa, Rubén D; Guldi, Dirk M

2018-05-10

We report on the synthesis, as well as photophysical and electrochemical characterization of a new family of pentacene derivatives, which are applied in n-type dye-sensitized solar cells (DSSCs). As far as the molecular structure of the pentacene is concerned, the synthetic design focuses on cyano acrylic tethered at the 13-position of the pentacene chromophore. The electrolyte composition features increasing amounts of Li+ ions as an additive. In general, the increase of Li+ concentrations extrinsically reduces the quasi Fermi level of the photoanode and as such facilitates the electron injection process. We demonstrate that pentacene derivatives give rise to a unique charge injection process, which is controlled by the positioning of the quasi Fermi level energies as a function of the Li+ concentration. As a result of the enhanced charge injection, device efficiencies as high as 1.5% are achieved, representing a 3-fold increase from previously reported efficiencies in pentacene-based DSSCs. These findings are supported by device analysis in combination with transient absorption and electrochemical impedance spectroscopy assays.

Novel strategy combining SYBR Green I with carbon nanotubes for highly sensitive detection of Salmonella typhimurium DNA.

PubMed

Mao, Pingdao; Ning, Yi; Li, Wenkai; Peng, Zhihui; Chen, Yongzhe; Deng, Le

2014-01-10

A simple, selective, sensitive and label-free fluorescent method for detecting trpS-harboring Salmonella typhimurium was developed in this study. This assay used the non-covalent interaction of single-stranded DNA (ssDNA) probes with SWNTs, since SWNTs can quench fluorescence. Fluorescence recovery (78% with 1.8 nM target DNA) was detected in the presence of target DNA as ssDNA probes detached from SWNTs hybridized with target DNA, and the resulting double-stranded DNA (dsDNA) intercalated with SYBR Green I (SG) dyes. The increasing fluorescence intensity reached 4.54-fold. In contrast, mismatched oligonucleotides (1- or 3-nt difference to the target DNA) did not contribute to significant fluorescent recovery, which demonstrated the specificity of the assay. The increasing fluorescence intensity increased 3.15-fold when purified PCR products containing complementary sequences of trpS gene were detected. These results confirmed the ability to use this assay for detecting real samples. Copyright © 2013 Elsevier Inc. All rights reserved.

Metroplex Optimization Model Expansion and Analysis: The Airline Fleet, Route, and Schedule Optimization Model (AFRS-OM)

NASA Technical Reports Server (NTRS)

Sherry, Lance; Ferguson, John; Hoffman, Karla; Donohue, George; Beradino, Frank

2012-01-01

This report describes the Airline Fleet, Route, and Schedule Optimization Model (AFRS-OM) that is designed to provide insights into airline decision-making with regards to markets served, schedule of flights on these markets, the type of aircraft assigned to each scheduled flight, load factors, airfares, and airline profits. The main inputs to the model are hedged fuel prices, airport capacity limits, and candidate markets. Embedded in the model are aircraft performance and associated cost factors, and willingness-to-pay (i.e. demand vs. airfare curves). Case studies demonstrate the application of the model for analysis of the effects of increased capacity and changes in operating costs (e.g. fuel prices). Although there are differences between airports (due to differences in the magnitude of travel demand and sensitivity to airfare), the system is more sensitive to changes in fuel prices than capacity. Further, the benefits of modernization in the form of increased capacity could be undermined by increases in hedged fuel prices

The gamma-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens

PubMed Central

2012-01-01

Background Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA) system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear. Methods We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo. Results The present study demonstrated that morphine challenge (3 mg/kg, s.c.) obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg) significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge. Conclusions Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse. PMID:22559224

The development of simple and sensitive small-molecule fluorescent probes for the detection of serum proteins after native polyacrylamide gel electrophoresis.

PubMed

Wang, Fangfang; Huang, Lingyun; Na, Na; He, Dacheng; Sun, Dezhi; Ouyang, Jin

2012-05-21

In this paper, a simple and sensitive small-molecule fluorescent probe, 2,5-dihydroxy-4'-dimethylaminochalcone (DHDMAC), was designed and synthesized for the detection of human serum proteins via hydrophobic interactions after polyacrylamide gel electrophoresis (PAGE). This probe produced lower fluorescence emission in the absence of proteins, and the emission intensity was significantly increased after the interaction with serum proteins. To demonstrate the imaging performance of this probe as a fluorescent dye, a series of experiments was conducted that included sensitivity comparison and 2D-PAGE. The results indicated that the sensitivity of DHDMAC staining is comparable to that of the most widely used fluorescent dye, SYPRO Ruby, and more protein spots (including thyroxine-binding globulin, angiotensinogen, afamin, zinc-α-2-glycoprotein and α-1-antichymotrypsin) were detected after 2D-PAGE. Therefore, DHDMAC is a good protein reporter due to its fast staining procedure, low detection limits and high resolution.

Evaluation of the Effects of Conjunctivochalasis Excision on Tear Stability and Contrast Sensitivity

PubMed Central

Qiu, Weiqiang; Zhang, Mingzhou; Xu, Ting; Liu, Ziyuan; Lv, Huibin; Wang, Wei; Li, Xuemin

2016-01-01

Conjunctivochalasis (CCh) disrupts tear flow and damages tear film stability. This study sought to evaluate the tear stability and contrast sensitivity of patients with CCh on whom CCh excision was performed. The study included 39 eyes from 39 patients; all patients had eyes with grade 2 or 3 CCh, underwent CCh excision, and were evaluated before and three months after the surgery. The evaluated variables included the ocular surface disease index (OSDI), the tear break-up time (TBUT), corneal fluorescein staining, corneal surface irregularity, Schirmer’s I test, the tear meniscus area (TMA), and contrast sensitivity. A follow-up of three months was achieved in 36 eyes for 36 patients. All parameters improved significantly after surgery (p < 0.05), except Schirmer’s I test, thus suggesting that CCh excision is an effective method for reconstructing the lower tear meniscus and improving both tear film stability and corneal surface irregularity. The results further demonstrated a simultaneous increase in contrast sensitivity after surgery. PMID:27892479

INF-γ sensitizes head and neck squamous cell carcinoma cells to chemotherapy-induced apoptosis and necroptosis through up-regulation of Egr-1.

PubMed

Xu, Bei; Shu, Yongqian; Liu, Peng

2014-11-01

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Acquired resistance to standard chemotherapy accounts for most of treatment failure. Here we demonstrate that Interferon-γ (INF-γ) may up-regulate Egr-1 gene expression in HNSCC cell line SCC-25. Forced expression of Egr-1 sensitizes SCC-25 cells to chemotherapy-induced apoptosis and necroptosis, a novel form of programmed cell death. Egr-1 up-regulation also significantly increases the production of Thrombospondin-1 (TSP-1), a matricellular glycoprotein which has been described to induce cell death in HNSCC. Moreover, INF-γ-induced sensitization of cells to chemotherapy-mediated cell death and TSP-1 production could be markedly abolished by Egr-1 silencing. The present investigation provides the first evidence that INF-γ may sensitize HNSCC cells to chemotherapy-induced apoptosis and necroptosis through up-regulation of Egr-1. These data support the combination use of INF-γ and cytotoxic drugs for HNSCC Therapy.

Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans

PubMed Central

Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Annamalai, Palam; Enerbäck, Sven; Lidell, Martin E.; Saraf, Manish K.; Labbe, Sebastien M.; Hurren, Nicholas M.; Yfanti, Christina; Chao, Tony; Andersen, Clark R.; Cesani, Fernando; Hawkins, Hal

2014-01-01

Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT+) men and five BAT-negative (BAT−) men under thermoneutral conditions and after prolonged (5–8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT+ group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans. PMID:25056438

Performance analysis of higher mode spoof surface plasmon polariton for terahertz sensing

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

Yao, Haizi; Tu, Wanli; Zhong, Shuncong, E-mail: zhongshuncong@hotmail.com

2015-04-07

We investigated the spoof surface plasmon polaritons (SSPPs) on 1D grooved metal surface for terahertz sensing of refractive index of the filling analyte through a prism-coupling attenuated total reflection setup. From the dispersion relation analysis and the finite element method-based simulation, we revealed that the dispersion curve of SSPP got suppressed as the filling refractive index increased, which cause the coupling resonance frequency redshifting in the reflection spectrum. The simulated results for testing various refractive indexes demonstrated that the incident angle of terahertz radiation has a great effect on the performance of sensing. Smaller incident angle will result in amore » higher sensitive sensing with a narrower detection range. In the meanwhile, the higher order mode SSPP-based sensing has a higher sensitivity with a narrower detection range. The maximum sensitivity is 2.57 THz/RIU for the second-order mode sensing at 45° internal incident angle. The proposed SSPP-based method has great potential for high sensitive terahertz sensing.« less

Data-driven sensitivity inference for Thomson scattering electron density measurement systems.

PubMed

Fujii, Keisuke; Yamada, Ichihiro; Hasuo, Masahiro

2017-01-01

We developed a method to infer the calibration parameters of multichannel measurement systems, such as channel variations of sensitivity and noise amplitude, from experimental data. We regard such uncertainties of the calibration parameters as dependent noise. The statistical properties of the dependent noise and that of the latent functions were modeled and implemented in the Gaussian process kernel. Based on their statistical difference, both parameters were inferred from the data. We applied this method to the electron density measurement system by Thomson scattering for the Large Helical Device plasma, which is equipped with 141 spatial channels. Based on the 210 sets of experimental data, we evaluated the correction factor of the sensitivity and noise amplitude for each channel. The correction factor varies by ≈10%, and the random noise amplitude is ≈2%, i.e., the measurement accuracy increases by a factor of 5 after this sensitivity correction. The certainty improvement in the spatial derivative inference was demonstrated.

An auto-biotinylated bifunctional protein nanowire for ultra-sensitive molecular biosensing.

PubMed

Men, Dong; Zhang, Zhi-Ping; Guo, Yong-Chao; Zhu, Duan-Hao; Bi, Li-Jun; Deng, Jiao-Yu; Cui, Zong-Qiang; Wei, Hong-Ping; Zhang, Xian-En

2010-12-15

In order to obtain an ultra-sensitive molecular biosensor, we designed an auto-biotinylated bifunctional protein nanowire (bFPNw) based on the self-assembly of a yeast amyloid protein, Sup35, to which protein G and a biotin acceptor peptide (BAP) were genetically fused. These auto-biotinylated bFPNws can transfer hundreds of commercially available diagnostic enzymes to an antigen-antibody complex via the biotin-avidin system, greatly enhancing the sensitivity of immune-biosensing. Compared to our previously reported seeding-induced bFPNws (Men et al., 2009), these auto-biotinylated bFPNws gave greater signal amplification, reduced non-specific binding and improved stability. The auto-biotinylated self-assembled bFPNw molecular biosensors were applied to detect Yersinia pestis (Y. pestis) F1 antigen and showed a 2000- to 4000-fold increase in sensitivity compared to traditional immunoassays, demonstrating the potential use of these self-assembling protein nanowires in biosensing. Copyright © 2010 Elsevier B.V. All rights reserved.

The Maillard Reaction Reduced the Sensitization of Tropomyosin and Arginine Kinase from Scylla paramamosain, Simultaneously.

PubMed

Han, Xin-Yu; Yang, Huang; Rao, Shi-Tao; Liu, Guang-Yu; Hu, Meng-Jun; Zeng, Bin-Chang; Cao, Min-Jie; Liu, Guang-Ming

2018-03-21

The Maillard reaction was established to reduce the sensitization of tropomyosin (TM) and arginine kinase (AK) from Scylla paramamosain, and the mechanism of the attenuated sensitization was investigated. In the present study, the Maillard reaction conditions were optimized for heating at 100 °C for 60 min (pH 8.5) with arabinose. A low level of allergenicity in mice was shown by the levels of allergen-specific antibodies, and more Th1 and less Th2 cells cytokines produced and associated transcription factors with the Maillard reacted allergen (mAllergen). The tolerance potency in mice was demonstrated by the increased ratio of Th1/Th2 cytokines. Moreover, mass spectrometry analysis showed that some key amino acids of IgE-binding epitopes (K 112 , R 125 , R 133 of TM; K 33 , K 118 , R 202 of AK) were modified by the Maillard reaction. The Maillard reaction with arabinose reduced the sensitization of TM and AK, which may be due to the masked epitopes.

Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction

PubMed Central

Choi, Hoon Young; Park, Hyeong Cheon

2015-01-01

Hypertension is a complex trait determined by both genetic and environmental factors and is a major public health problem due to its high prevalence and concomitant increase in the risk for cardiovascular disease. With the recent large increase of dietary salt intake in most developed countries, the prevalence of hypertension increases tremendously which is about 30% of the world population. There is substantial evidence that suggests some people can effectively excrete high dietary salt intake without an increase in arterial BP, and another people cannot excrete effectively without an increase in arterial BP. Salt sensitivity of BP refers to the BP responses for changes in dietary salt intake to produce meaningful BP increases or decreases. The underlying mechanisms that promote salt sensitivity are complex and range from genetic to environmental influences. The phenotype of salt sensitivity is therefore heterogeneous with multiple mechanisms that potentially link high salt intake to increases in blood pressure. Moreover, excess salt intake has functional and pathological effects on the vasculature that are independent of blood pressure. Epidemiologic data demonstrate the role of high dietary salt intake in mediating cardiovascular and renal morbidity and mortality. Almost five decades ago, Guyton and Coleman proposed that whenever arterial pressure is elevated, pressure natriuresis enhances the excretion of sodium and water until blood volume is reduced sufficiently to return arterial pressure to control values. According to this hypothesis, hypertension can develop only when something impairs the excretory ability of sodium in the kidney. However, recent studies suggest that nonosmotic salt accumulation in the skin interstitium and the endothelial dysfunction which might be caused by the deterioration of vascular endothelial glycocalyx layer (EGL) and the epithelial sodium channel on the endothelial luminal surface (EnNaC) also play an important role in nonosmotic storage of salt. These new concepts emphasize that sodium homeostasis and salt sensitivity seem to be related not only to the kidney malfunction but also to the endothelial dysfunction. Further investigations will be needed to assess the extent to which changes in the sodium buffering capacity of the skin interstitium and develop the treatment strategy for modulating the endothelial dysfunction. PMID:26240595

Cerenkov luminescence endoscopy: Improved molecular sensitivity with β --emitting radiotracers

DOE PAGES

Carpenter, Colin M.; Ma, Xiaowei; Liu, Hongguang; ...

2014-10-09

Cerenkov luminescence endoscopy (CLE) is an optical technique that captures the Cerenkov photons emitted from highly energetic moving charged particles (β + or β $-$) and can be used to monitor the distribution of many clinically available radioactive probes. A main limitation of CLE is its limited sensitivity to small concentrations of radiotracer, especially when used with a light guide. We investigated the improvement in the sensitivity of CLE brought about by using a β $-$ radiotracer that improved Cerenkov signal due to both higher β-particle energy and lower γ noise in the imaging optics because of the lack ofmore » positron annihilation. Here, the signal-to-noise ratio (SNR) of 90Y was compared with that of 18F in both phantoms and small-animal tumor models. Sensitivity and noise characteristics were demonstrated using vials of activity both at the surface and beneath 1 cm of tissue. Rodent U87MG glioma xenograft models were imaged with radiotracers bound to arginine-glycine-aspartate (RGD) peptides to determine the SNR. As a result, γ noise from 18F was demonstrated by both an observed blurring across the field of view and a more pronounced fall-off with distance. A decreased γ background and increased energy of the β particles resulted in a 207-fold improvement in the sensitivity of 90Y compared with 18F in phantoms. 90Y-bound RGD peptide produced a higher tumor-to-background SNR than 18F in a mouse model. In conclusion, the use of 90Y for Cerenkov endoscopic imaging enabled superior results compared with an 18F radiotracer.« less

Recording membrane potential changes through photoacoustic voltage sensitive dye

NASA Astrophysics Data System (ADS)

Zhang, Haichong K.; Kang, Jeeun; Yan, Ping; Abou, Diane S.; Le, Hanh N. D.; Thorek, Daniel L. J.; Kang, Jin U.; Gjedde, Albert; Rahmim, Arman; Wong, Dean F.; Loew, Leslie M.; Boctor, Emad M.

2017-03-01

Monitoring of the membrane potential is possible using voltage sensitive dyes (VSD), where fluorescence intensity changes in response to neuronal electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. In contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near infrared light excitation and ultrasound detection. In this work, we develop the theoretical concept whereby the voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. Based on this concept, we synthesized a novel near infrared photoacoustic VSD (PA-VSD) whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. With a 3-9 μM VSD concentration, we measured a PA signal increase in the range of 5.3 % to 18.1 %, and observed a corresponding signal reduction in fluorescence emission of 30.0 % to 48.7 %. A theoretical model successfully accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate the voltage sensing capability of the dye, but also indicate the necessity of considering both fluorescence and absorbance spectral sensitivities in order to optimize the characteristics of improved photoacoustic probes. Together, our results demonstrate photoacoustic sensing as a potential new modality for sub-second recording and external imaging of electrophysiological and neurochemical events in the brain.

Recovery of Spectrally Overlapping QPSK Signals Using a Nonlinear Optoelectronic Filter

DTIC Science & Technology

2017-03-19

Spectrally Overlapping QPSK Signals Using a Nonlinear Optoelectronic Filter William Loh, Siva Yegnanarayanan, Kenneth E. Kolodziej, and Paul...recovery of a weak QPSK signal buried 35-dB beneath an interfering QPSK signal having an overlapping spectrum. This nonlinear optoelectronic filter ...from increased detection sensitivity. Here, we demonstrate an optoelectronic filter that enables the detection of a desired signal hidden beneath a

Breast Cancer Screening in a Low Income Managed Care Population

DTIC Science & Technology

1998-10-01

is the only screening test to be demonstrated by prospective clinical trial to decrease cancer mortality (11-13). Its efficiency and relative safety...increase in the utilization of mammography in conjunction with clinical breast exam, the technology continues to be underutilized, especially among certain...Using familiar sites for special program activities e.g. churches, clinic sites; Developing culturally-sensitive information at the appropriate literacy

The disinhibitory zone of the striate neuron receptive field and its sensitivity to cross-like figures.

PubMed

Lazareva, N A; Shevelev, I A; Novikova, R V; Tikhomirov, A S; Sharaev, G A; Tsutskiridze, D Yu

2002-01-01

Acute experiments on immobilized anesthetized cats were used to confirm the suggestion that the sensitivity of many neurons on the primary visual cortex to cross-shaped, angular, and Y-shaped figures may be determined by the presence within their receptive fields of disinhibitory zones, which block end-stopping inhibition. A total of 55 neurons (84 functions, i.e.. on and off responses) were used for studies of sensitivity to crosses, and responses to single bars of different lengths were compared before and after stimulation of an additional lateral zone of the field (the presumptive disinhibitory zone), which was located in terms of responses to crosses. Seventeen of the 55 cells in which increases in the length of a single bar decreased responses, i.e., which demonstrated end-stopping inhibition, showed significant increases in responses (by an average factor of 2.06 +/- 0.16) during simultaneous stimulation of the lateral zone of the receptive field, which we interpreted as a disinhibitory effect on end-stopping inhibition. These data provide the first direct evidence for the role of end-stopping inhibition and its blockade by the disinhibitory zone of the receptive field in determining the sensitivity of some neurons in the primary visual cortex of the cat to cross-shaped figures.