Critical thresholds in sea lice epidemics: evidence, sensitivity and subcritical estimation

PubMed Central

Frazer, L. Neil; Morton, Alexandra; Krkošek, Martin

2012-01-01

Host density thresholds are a fundamental component of the population dynamics of pathogens, but empirical evidence and estimates are lacking. We studied host density thresholds in the dynamics of ectoparasitic sea lice (Lepeophtheirus salmonis) on salmon farms. Empirical examples include a 1994 epidemic in Atlantic Canada and a 2001 epidemic in Pacific Canada. A mathematical model suggests dynamics of lice are governed by a stable endemic equilibrium until the critical host density threshold drops owing to environmental change, or is exceeded by stocking, causing epidemics that require rapid harvest or treatment. Sensitivity analysis of the critical threshold suggests variation in dependence on biotic parameters and high sensitivity to temperature and salinity. We provide a method for estimating the critical threshold from parasite abundances at subcritical host densities and estimate the critical threshold and transmission coefficient for the two epidemics. Host density thresholds may be a fundamental component of disease dynamics in coastal seas where salmon farming occurs. PMID:22217721

Low to high confinement transition theory of finite-beta drift-wave driven shear flow and its comparison with data from DIII-D

NASA Astrophysics Data System (ADS)

Guzdar, P. N.; Kleva, R. G.; Groebner, R. J.; Gohil, P.

2004-03-01

Shear flow stabilization of edge turbulence in tokamaks has been the accepted paradigm for the improvement in confinement observed in high (H) confinement mode plasmas. Results on the generation of zonal flow and fields in finite β plasmas are presented. This theory yields a criterion for bifurcation from low to high (L-H) confinement mode, proportional to Te/√Ln , where Te is the electron temperature and Ln is the density scale-length at the steepest part of the density gradient. When this parameter exceeds a critical value (mostly determined by the strength of the toroidal magnetic field), the transition occurs. The predicted threshold based on this parameter shows good agreement with edge measurements on discharges undergoing L-H transitions in DIII-D [J. L. Luxon, R. Anderson, F. Batty et al., in Proceedings of the 11th Conference on Plasma Physics and Controlled Fusion Research, 1986 (International Atomic Energy Agency, Vienna, 1987), Vol. I, p. 159]. The observed differences in the transitions with the reversal of the toroidal magnetic field are reconciled in terms of this critical parameter due to the differences in the density gradient scale-lengths in the edge. The theory also provides a possible explanation for lowered threshold power, pellet injection H modes in DIII-D, thereby providing a unified picture of the varied observations on the L-H transition.

Effect of Electron Seeding on Experimentally Measured Multipactor Discharge Threshold

NASA Astrophysics Data System (ADS)

Noland, Jonathan; Graves, Timothy; Lemon, Colby; Looper, Mark; Farkas, Alex

2012-10-01

Multipactor is a vacuum phenomenon in which electrons, moving in resonance with an externally applied electric field, impact material surfaces. If the number of secondary electrons created per primary electron impact averages more than unity, the resonant interaction can lead to an electron avalanche. Multipactor is a generally undesirable phenomenon, as it can cause local heating, absorb power, or cause detuning of RF circuits. In order to increase the probability of multipactor initiation, test facilities often employ various seeding sources such as radioactive sources (Cesium 137, Strontium 90), electron guns, or photon sources. Even with these sources, the voltage for multipactor initiation is not certain as parameters such as material type, RF pulse length, and device wall thickness can all affect seed electron flux and energy in critical gap regions, and hence the measured voltage threshold. This study investigates the effects of seed electron source type (e.g., photons versus beta particles), material type, gap size, and RF pulse length variation on multipactor threshold. In addition to the experimental work, GEANT4 simulations will be used to estimate the production rate of low energy electrons (< 5 keV) by high energy electrons and photons. A comparison of the experimental fluxes to the typical energetic photon and particle fluxes experienced by spacecraft in various orbits will also be made. Initial results indicate that for a simple, parallel plate device made of aluminum, there is no threshold variation (with seed electrons versus with no seed electrons) under continuous-wave RF exposure.

Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice.

PubMed

Hamelet, J; Aït-Yahya-Graison, E; Matulewicz, E; Noll, C; Badel-Chagnon, A; Camproux, A-C; Demuth, K; Paul, J-L; Delabar, J M; Janel, N

2007-12-01

Hyperhomocysteinaemia is a metabolic disorder associated with the development of premature atherosclerosis. Among the determinants which predispose to premature thromboembolic and atherothrombotic events, serum activity of paraoxonase 1, mainly synthesized in the liver, has been shown to be a predictor of cardiovascular disease and to be negatively correlated with serum homocysteine levels in human. Even though treatments of hyperhomocysteinaemic patients ongoing cardiovascular complications are commonly used, it still remains unclear above which homocysteine level a preventive therapy should be started. In order to establish a threshold of plasma homocysteine concentration we have analyzed the hepatic cystathionine beta synthase and paraoxonase 1 activities in a moderate to intermediate murine model of hyperhomocysteinaemia. Using wild type and heterozygous cystathionine beta synthase deficient mice fed a methionine enriched diet or a control diet, we first studied the link between cystathionine beta synthase and paraoxonase 1 activities and plasma homocysteine concentration. Among the animals used in this study, we observed a negative correlation between plasma homocysteine level and cystathionine beta synthase activity (rho=-0.52, P=0.0008) or paraoxonase 1 activity (rho=-0.49, P=0.002). Starting from these results, a homocysteine cut-off value of 15 microm has been found for both cystathionine beta synthase (P=0.0003) and paraoxonase 1 (P=0.0007) activities. Our results suggest that both cystathionine beta synthase and paraoxonase 1 activities are significantly decreased in mice with a plasma homocysteine value greater than 15 microm. In an attempt to set up preventive treatment for cardiovascular disease our results indicate that treatments should be started from 15 microm of plasma homocysteine.

Through the central V2, not V1 receptors influencing the endogenous opiate peptide system, arginine vasopressin, not oxytocin in the hypothalamic paraventricular nucleus involves in the antinociception in the rat.

PubMed

Yang, Jun; Chen, Jian-min; Song, Cao-You; Liu, Wen-Yan; Wang, Gen; Wang, Cheng-hai; Lin, Bao-Chen

2006-01-19

Our previous study has proven that hypothalamic paraventricular nucleus (PVN) played a role in the antinociception. The central bioactive substances involving in the PVN regulating antinociception were investigated in the rat. The results showed that electrical stimulation of the PVN increased the pain threshold, and L-glutamate sodium injection into the PVN elevated the pain threshold, but the PVN cauterization decreased the pain threshold; pain stimulation raised the arginine vasopressin (AVP), not oxytocin (OXT), leucine-enkephalin (L-Ek), beta-endorphin (beta-Ep) and DynorphinA1-13 (DynA1-13) concentrations in the PVN tissue using micropunch method, heightened AVP, L-Ek, beta-Ep and DynA1-13, not OXT concentrations in the PVN perfuse liquid, and reduced the number of AVP-, not OXT, L-Ek, beta-Ep and DynA1-13-immunoreactive neurons in the PVN especially in the posterior magnocellular part of the PVN using immunocytochemistry. There was a negative relationship between the PVN AVP concentration and the pain threshold; pain stimulation enhanced the AVP, not OXT mRNA expression in the PVN using in situ hybridization and RT-PCR; intraventricular injection of anti-AVP serum completely reversed L-glutamate sodium injection into the PVN-induced antinociception, and administration of naloxone - the opiate peptide antagonist, partly blocked this L-glutamate sodium effect, but anti-OXT serum pretreatment did not influence this L-glutamate sodium effect; L-glutamate sodium injection into the PVN-induced analgesia was inhibited by V2 receptor antagonist - d(CH2)5[D-Ile2, Ile4, Ala-NH2(9)]AVP, not V1 receptor antagonist - d(CH2)5Tyr(Me)AVP. The data suggested that the PVN was limited to the central AVP, not OXT, which was through V2, not V1 receptors influencing the endogenous opiate peptide system, to regulate antinociception.

Neurofeedback in three patients in the state of unresponsive wakefulness.

PubMed

Keller, Ingo; Garbacenkaite, Ruta

2015-12-01

Some severely brain injured patients remain unresponsive, only showing reflex movements without any response to command. This syndrome has been named unresponsive wakefulness syndrome (UWS). The objective of the present study was to determine whether UWS patients are able to alter their brain activity using neurofeedback (NFB) technique. A small sample of three patients received a daily session of NFB for 3 weeks. We applied the ratio of theta and beta amplitudes as a feedback variable. Using an automatic threshold function, patients heard their favourite music whenever their theta/beta ratio dropped below the threshold. Changes in awareness were assessed weekly with the JFK Coma Recovery Scale-Revised for each treatment week, as well as 3 weeks before and after NFB. Two patients showed a decrease in their theta/beta ratio and theta-amplitudes during this period. The third patient showed no systematic changes in his EEG activity. The results of our study provide the first evidence that NFB can be used in patients in a state of unresponsive wakefulness.

The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

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

Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

2006-01-13

Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, andmore » the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.« less

Function of Several Critical Amino Acids in Human Pyruvate Dehydrogenase Revealed by Its Structure

NASA Technical Reports Server (NTRS)

Korotchkina, Lioubov G.; Ciszak, E.; Patel, M.

2004-01-01

Pyruvate dehydrogenase (E1), an alpha 2 beta 2 tetramer, catalyzes the oxidative decarboxylation of pyruvate and reductive acetylation of lipoyl moieties of the dihydrolipoamide acetyltransferase. The roles of beta W135, alpha P188, alpha M181, alpha H15 and alpha R349 of E1 determined by kinetic analysis were reassessed by analyzing the three-dimensional structure of human E1. The residues identified above are found to play a structural role rather than being directly involved in catalysis: beta W135 is the center residue in the hydrophobic interaction between beta and beta' subunits; alpha P188 and alpha M181 are critical for the conformation of the TPP-binding motif and interaction between alpha and beta subunits; alpha H15, is necessary for the organization of the N-terminus of alpha and alpha'; subunits and alpha R349 supports the interaction of the C-terminus of the alpha subunits with the beta subunits. Analysis of several critical E1 residues confirms the importance of residues distant from the active site for subunit interactions and enzyme function.

Beta- and gamma-dose measurements of the Godiva IV critical assembly.

PubMed

Hankins, D E

1984-03-01

To aid in the re-evaluation of an exposure that occurred in 1963, information was required on the response of film badges to the beta- and gamma-ray doses from a critical assembly. Of particular interest was the beta spectra from the assembly. The techniques used and the results obtained in this study are of interest to health physicists at facilities where exposures to betas occur. The dose rates from the Los Alamos National Laboratory Godiva IV Critical Assembly were measured at numerous distances from the assembly four and 12 days following a burst. Information was obtained on the beta-particle spectra using absorption curve studies. The beta/gamma dose-rate ratio as a function of distance from the assembly was determined. Shielding provided by various metals, gloves and clothing was measured. The beta- and gamma-ray doses measured were compared with a film packet used in the past at the Nevada Test Site with two types of current TLD personnel badges. Measurements made with a commercial thin-window ion chamber instrument are compared with the dose rates obtained using other dosimeters.

The role of IL-6 and IL-1beta in painful perineural inflammatory neuritis.

PubMed

Eliav, Eli; Benoliel, Rafael; Herzberg, Uri; Kalladka, Mythili; Tal, Michael

2009-05-01

Inflammation along a nerve trunk (perineural inflammation), without detectable axonal damage, has been shown to induce transient pain in the organ supplied by the nerve. The aims of the present study were to study the role IL-6 and IL-1beta, in pain induced by perineural inflammation. IL-6 and IL-1beta secretion from rat's sciatic nerves, L-5 Dorsal Root Ganglia (DRG), and the hind paw skin, 3 and 8 days following exposure of the nerve to Complete Freund's Adjuvant (CFA), were measured using ELISA method. Hind paw tactile-allodynia, mechano-hyperalgesia, heat-allodynia and electrical detection thresholds were tested up to 8 days following the application of CFA, IL-6 or IL-1beta adjacent to the sciatic nerve trunk. Employing electrophysiological recording, saphenous nerve spontaneous activity, nerve trunk mechano-sensitivity and paw tactile detection threshold (determined by recording action potential induced by the lowest mechanical stimulus) were assessed 3 and 8 days following exposure of the nerve trunk to CFA, IL-6, or IL-1beta. IL-6 and IL-1beta secretion from the nerve was significantly elevated on the 3rd day post-operation (DPO). On the 8th DPO, IL-6 levels returned to baseline while IL-1beta levels remained significantly elevated. The DRG cytokine's level was increased on the 3rd and 8th DPOs, contralateral cytokine's level was increased on the 3rd DPO. The skin IL-6 level was increased bilaterally on the 3rd DPO and returned to baseline on the 8th DPO. IL-1beta levels increased in the affected side on the 3rd and bilaterally on the 8th DPO. Direct application of IL-6 or CFA on the sciatic nerve induced significant hind paw tactile-allodynia from the 1st to 5th DPOs, reduced electrical detection threshold from the 1st to 3rd DPOs, mechano-hyperalgesia from 3rd to 5th DPOs and heat-allodynia on the 3rd DPO. Direct application of IL-1beta induced paw tactile and heat-allodynia on the 7-8th DPOs and mechano-hyperalgesia on the 5-8th DPOs. Perineural inflammation significantly increased spontaneous activity myelinated fibres 3 and 8 days following the application. Direct application of IL-6 induced elevation of spontaneous activity on the 3rd while IL-1beta on the 8th DPO. Nerve mechano-sensitivity was significantly increased on the 3rd day following exposure to CFA and IL-6 and on the 8th following CFA application. The rat's paw lowest mechanical force necessary for induction of action potential, was significantly reduced 3 days following CFA application. IL-6 and IL-1beta play an important role in pain induced by perineural inflammation. IL-6 activity is more prominent immediately following application (2-5th DPOs), while IL-1beta, activity is more significant in a later stage (5-8th DPOs).

Mutational analysis of immunoglobulin E-binding epitopes of beta-casein and beta-lactoglobulin showed a heterogeneous pattern of critical amino acids between individual patients and pooled sera.

PubMed

Cocco, R R; Järvinen, K-M; Han, N; Beyer, K; Sampson, H A

2007-06-01

For immunotherapeutic approaches, 'critical' amino acids (AAs) within allergenic epitopes are replaced with alternate AAs to eliminate IgE antibody binding. To determine the critical AAs for IgE binding in beta-casein and beta-lactoglobulin (BLG). Peptides of 10-14 AAs in length were synthesized on a derivatized cellulose membrane with single AA substitutions (alanine or glycine) at each position. Membranes were incubated with a pool of sera from 15 cow's milk-allergic patients and individual sera from six of the 15 patients. In cases where no decrease in binding occurred with a single AA substitution, peptides with two AA substitutions were generated and labelled. Using pooled patient sera, single AA substitutions led to complete elimination of binding to six of 11 peptides for beta-casein and to all six peptides for BLG. Substituting two AAs led to an elimination of binding to four of the remaining five beta-casein epitopes. However, in three of the 11 modified beta-casein peptides and five of the six BLG peptides, no decrease in IgE binding occurred in at least one individual patient. For these patients, critical AAs other than those defined by the patient serum pool were identified, indicating a heterogeneous pattern of IgE recognition. These results indicate that AAs critical for IgE binding are more heterogeneous than initially defined by pooled milk-allergic patient sera. For future immunotherapeutic interventions with mutated peptides, critical AAs should also be identified with individual patient sera to account for heterogeneity of IgE binding between patients.

Development of a Cerenkov radiation sensor to detect low-energy beta-particles.

PubMed

Yoo, Wook Jae; Han, Ki-Tek; Shin, Sang Hun; Seo, Jeong Ki; Jeon, Dayeong; Lee, Bongsoo

2013-11-01

We fabricated a novel fiber-optic Cerenkov radiation sensor using a Cerenkov radiator for measuring beta-particles. Instead of employing a scintillator, transparent liquids having various refractive indices were used as a Cerenkov radiator to serve as a sensing material. The experimental results showed that the amount of Cerenkov radiation due to the interaction with beta-particles increased as the refractive index of the Cerenkov radiator was increased as a results of a decrease of the Cerenkov threshold energy for electrons. © 2013 Elsevier Ltd. All rights reserved.

Latent transforming growth factor beta1 activation in situ: quantitative and functional evidence after low-dose gamma-irradiation

NASA Technical Reports Server (NTRS)

Ehrhart, E. J.; Segarini, P.; Tsang, M. L.; Carroll, A. G.; Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1997-01-01

The biological activity of transforming growth factor beta1 (TGF-beta) is controlled by its secretion as a latent complex in which it is noncovalently associated with latency-associated peptide (LAP). Activation is the extracellular process in which TGF-beta is released from LAP, and is considered to be a primary regulatory control. We recently reported rapid and persistent changes in TGF-beta immunoreactivity in conjunction with extracellular matrix remodeling in gamma-irradiated mouse mammary gland. Our hypothesis is that these specific changes in immunoreactivity are indicative of latent TGF-beta activation. In the present study, we determined the radiation dose response and tested whether a functional relationship exists between radiation-induced TGF-beta and collagen type III remodeling. After radiation exposures as low as 0.1 Gy, we detected increased TGF-beta immunoreactivity in the mammary epithelium concomitant with decreased LAP immunostaining, which are events consistent with activation. Quantitative image analysis demonstrated a significant (P=0.0005) response at 0.1 Gy without an apparent threshold and a linear dose response to 5 Gy. However, in the adipose stroma, loss of LAP demonstrated a qualitative threshold at 0.5 Gy. Loss of LAP paralleled induction of collagen III immunoreactivity in this tissue compartment. We tested whether TGF-beta mediates collagen III expression by treating animals with TGF-beta panspecific monoclonal antibody, 1D11.16, administered i.p. shortly before irradiation. Radiation-induced collagen III staining in the adipose stroma was blocked in an antibody dose-dependent manner, which persisted through 7 days postirradiation. RNase protection assay revealed that radiation-induced elevation of total gland collagen III mRNA was also blocked by neutralizing antibody treatment. These data provide functional confirmation of the hypothesis that radiation exposure leads to latent TGF-beta activation, support our interpretation of the reciprocal shift in immunoreactivity as evidence of activation, and implicate TGF-beta as a mediator of tissue response to ionizing radiation. The sensitivity of activation to low radiation doses points to a potential role for TGF-beta in orchestrating tissue response to oxidative stress. As such, radiation may be useful as a probe to delineate the consequences of latent TGF-beta activation in situ.

A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats.

PubMed

Nylen, Kirk; Likhodii, Sergei; Abdelmalik, Peter A; Clarke, Jasper; Burnham, W McIntyre

2005-08-01

The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.

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

Zhu Tangkui, E-mail: zhutangkui@sohu.com; Li, Miaoquan, E-mail: honeymli@nwpu.edu.cn

Effect of hydrogen content on the lattice parameter of Ti-6Al-4V alloy has been investigated by X-ray diffraction. The experimental results show that the solution of hydrogen in the Ti-6Al-4V alloy affects significantly on the lattice parameters of {alpha}, {beta} and {delta} phases, especially the {beta} phase. Furthermore, the critical hydrogen content of {delta} hydride formation for Ti-6Al-4V alloy is 0.385 wt.%. When the hydrogen content is lower than the critical hydrogen content, the {delta} hydride cannot precipitate and the lattice parameter ({alpha}) of {beta} phase linearly increases with the increasing of hydrogen content. When the hydrogen content is higher thanmore » the critical hydrogen content, the {delta} hydride precipitates and the lattice parameter ({alpha}) of {beta} phase varies inconspicuously with hydrogen content. In addition, the effects of lattice variations and {delta} hydride formation on microstructure are discussed. The {alpha}/{beta} interfaces of lamellar transformed {beta} phase become fuzzy with the increasing of hydrogen content because of the lattice expansion of {beta} phase. Compared with that of the Ti-6Al-4V alloy at low hydrogen content ({<=} 0.385 wt.%), the contrasts of primary {alpha} phase and transformed {beta} phase of Ti-6Al-4V alloy at high hydrogen content ({>=} 0.385 wt.%) were completely reversed due to the formation of {delta} hydride. - Research Highlights: {yields} A novel method for determining {delta} hydride in Ti-6Al-4V alloy is presented. {yields} The critical hydrogen content of {delta} hydride formation is 0.385 wt.%. {yields} The lattice parameter of {beta} phase can be expressed as follows: a=0.323(1+9.9x10{sup -2}C{sub H}) . {yields} Precipitation of {delta} hydride has a significant influence on the microstructure. {yields} The {alpha}/{beta} interfaces of transformed {beta} phase became fuzzy in the hydrogenated alloy.« less

Stream amphibians as metrics of critical biological thresholds in the Pacific Northwest, U.S.A.: a response to Kroll et al.

Treesearch

H. H. Welsh; G. R. Hodgson

2009-01-01

1. Kroll, Hayes & MacCracken (in press) Concerns regarding the use of amphibians as metrics of critical biological thresholds: a comment on Welsh and Hodgson 2008. Freshwater Biology, criticised our paper [Welsh & Hodgson (2008) Amphibians as metrics of critical biological thresholds in forested headwater streams of the...

Current-induced domain wall motion in permalloy nanowires with a rectangular cross-section

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

Ai, J. H.; Miao, B. F.; Sun, L.

2011-11-01

We performed micromagnetic simulations of the current-induced domain wall motion in permalloy nanowires with rectangular cross-section. In the absence of the nonadiabatic spin-transfer term, a threshold current, J{sub c} is required to drive the domain wall moving continuously. We find that J{sub c} is proportional to the maximum cross product of the demagnetization field and magnetization orientation of the domain wall and the domain wall width. With varying both the wire thickness and width, a minimum threshold current in the order of 10{sup 6} A/cm{sup 2} is obtained when the thickness is equivalent to the wire width. With the nonadiabaticmore » spin-transfer term, the calculated domain wall velocity {nu} equals to the adiabatic spin transfer velocity u when the current is far above the Walker limit J{sub w}. Below J{sub w}, {nu}=({beta}/{alpha})u, where {beta} is the nonadiabatic parameter and {alpha} is the damping factor. For different {beta}, we find the Walker limit can be scaled as J{sub w}=({alpha}/{beta}-{alpha})J{sub c}. Our simulations agree well with the one dimensional analytical calculation, suggesting the findings are the general behaviors of the systems in this particular geometry.« less

Efficient 2(nd) and 4(th) harmonic generation of a single-frequency, continuous-wave fiber amplifier.

PubMed

Sudmeyer, Thomas; Imai, Yutaka; Masuda, Hisashi; Eguchi, Naoya; Saito, Masaki; Kubota, Shigeo

2008-02-04

We demonstrate efficient cavity-enhanced second and fourth harmonic generation of an air-cooled, continuous-wave (cw), single-frequency 1064 nm fiber-amplifier system. The second harmonic generator achieves up to 88% total external conversion efficiency, generating more than 20-W power at 532 nm wavelength in a diffraction-limited beam (M(2) < 1.05). The nonlinear medium is a critically phase-matched, 20-mm long, anti-reflection (AR) coated LBO crystal operated at 25 degrees C. The fourth harmonic generator is based on an AR-coated, Czochralski-grown beta-BaB(2)O(4) (BBO) crystal optimized for low loss and high damage threshold. Up to 12.2 W of 266-nm deep-UV (DUV) output is obtained using a 6-mm long critically phase-matched BBO operated at 40 degrees C. This power level is more than two times higher than previously reported for cw 266-nm generation. The total external conversion efficiency from the fundamental at 1064 nm to the fourth harmonic at 266 nm is >50%.

Forbidden Mass Ranges for Shower Meteoroids

NASA Technical Reports Server (NTRS)

Moorhead, Althea V.

2017-01-01

Burns et al. (1979) use the parameter beta to describe the ratio of radiation pressure to gravity for a particle in the Solar System. The central potential that these particles experience is effectively reduced by a factor of (1- beta ), which in turn lowers the escape velocity. Burns et al. (1979) derived a simple expression for the value of beta at which particles ejected from a comet follow parabolic orbits and thus leave the Solar System; we expand on this to derive an expression for critical beta values that takes ejection velocity into account, assuming geometric optics. We use our expression to compute the critical value and corresponding mass for cometary ejecta leading, trailing, and following the parent comet's nucleus for 10 major meteor showers. Finally, we numerically solve for critical beta values in the case of non-geometric optics. These values determine the mass regimes within which meteoroids are ejected from the Solar System and therefore cannot contribute to meteor showers.

Beta Atomic Contacts: Identifying Critical Specific Contacts in Protein Binding Interfaces

PubMed Central

Liu, Qian; Kwoh, Chee Keong; Hoi, Steven C. H.

2013-01-01

Specific binding between proteins plays a crucial role in molecular functions and biological processes. Protein binding interfaces and their atomic contacts are typically defined by simple criteria, such as distance-based definitions that only use some threshold of spatial distance in previous studies. These definitions neglect the nearby atomic organization of contact atoms, and thus detect predominant contacts which are interrupted by other atoms. It is questionable whether such kinds of interrupted contacts are as important as other contacts in protein binding. To tackle this challenge, we propose a new definition called beta (β) atomic contacts. Our definition, founded on the β-skeletons in computational geometry, requires that there is no other atom in the contact spheres defined by two contact atoms; this sphere is similar to the van der Waals spheres of atoms. The statistical analysis on a large dataset shows that β contacts are only a small fraction of conventional distance-based contacts. To empirically quantify the importance of β contacts, we design βACV, an SVM classifier with β contacts as input, to classify homodimers from crystal packing. We found that our βACV is able to achieve the state-of-the-art classification performance superior to SVM classifiers with distance-based contacts as input. Our βACV also outperforms several existing methods when being evaluated on several datasets in previous works. The promising empirical performance suggests that β contacts can truly identify critical specific contacts in protein binding interfaces. β contacts thus provide a new model for more precise description of atomic organization in protein quaternary structures than distance-based contacts. PMID:23630569

Simulated Critical Differences for Speech Reception Thresholds

ERIC Educational Resources Information Center

Pedersen, Ellen Raben; Juhl, Peter Møller

2017-01-01

Purpose: Critical differences state by how much 2 test results have to differ in order to be significantly different. Critical differences for discrimination scores have been available for several decades, but they do not exist for speech reception thresholds (SRTs). This study presents and discusses how critical differences for SRTs can be…

Analysis of Critical Mass in Threshold Model of Diffusion

NASA Astrophysics Data System (ADS)

Kim, Jeehong; Hur, Wonchang; Kang, Suk-Ho

2012-04-01

Why does diffusion sometimes show cascade phenomena but at other times is impeded? In addressing this question, we considered a threshold model of diffusion, focusing on the formation of a critical mass, which enables diffusion to be self-sustaining. Performing an agent-based simulation, we found that the diffusion model produces only two outcomes: Almost perfect adoption or relatively few adoptions. In order to explain the difference, we considered the various properties of network structures and found that the manner in which thresholds are arrayed over a network is the most critical factor determining the size of a cascade. On the basis of the results, we derived a threshold arrangement method effective for generation of a critical mass and calculated the size required for perfect adoption.

Rainfall Threshold for Flash Flood Early Warning Based on Rational Equation: A Case Study of Zuojiao Watershed in Yunnan Province

NASA Astrophysics Data System (ADS)

Li, Q.; Wang, Y. L.; Li, H. C.; Zhang, M.; Li, C. Z.; Chen, X.

2017-12-01

Rainfall threshold plays an important role in flash flood warning. A simple and easy method, using Rational Equation to calculate rainfall threshold, was proposed in this study. The critical rainfall equation was deduced from the Rational Equation. On the basis of the Manning equation and the results of Chinese Flash Flood Survey and Evaluation (CFFSE) Project, the critical flow was obtained, and the net rainfall was calculated. Three aspects of the rainfall losses, i.e. depression storage, vegetation interception, and soil infiltration were considered. The critical rainfall was the sum of the net rainfall and the rainfall losses. Rainfall threshold was estimated after considering the watershed soil moisture using the critical rainfall. In order to demonstrate this method, Zuojiao watershed in Yunnan Province was chosen as study area. The results showed the rainfall thresholds calculated by the Rational Equation method were approximated to the rainfall thresholds obtained from CFFSE, and were in accordance with the observed rainfall during flash flood events. Thus the calculated results are reasonable and the method is effective. This study provided a quick and convenient way to calculated rainfall threshold of flash flood warning for the grass root staffs and offered technical support for estimating rainfall threshold.

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

Song, Hae Jin; Park, Joongkyu; Seo, Su Ryeon

Down syndrome is mainly caused by a trisomy of chromosome 21. The Down syndrome critical region 2 (DSCR2) gene is located within a part of chromosome 21, the Down syndrome critical region (DSCR). To investigate the function of DSCR2, we sought to identify DSCR2-interacting proteins using yeast two-hybrid assays. A human fetal brain cDNA library was screened, and DSCR2 was found to interact with a member of the nuclear receptor superfamily, peroxisome proliferator-activated receptor {beta}, (PPAR{beta}). A co-immunoprecipitation assay demonstrated that DSCR2 physically interacts with PPAR{beta} in mammalian HEK293 cells. DSCR2 also inhibited the ligand-induced transcriptional activity of PPAR{beta}. Furthermore,more » PPAR{beta} also decreased the solubility of DSCR2, which increased levels of insoluble DSCR2.« less

Implications inferred from anisotropy parameter of proton distributions related to EMIC waves in the inner magnetosphere.

NASA Astrophysics Data System (ADS)

Noh, S. J.; Lee, D. Y.

2017-12-01

In the classic theory of wave-particle resonant interaction, anisotropy parameter of proton distribution is considered as an important factor to determine an instability such as ion cyclotron instability. The particle distribution function is often assumed to be a bi-Maxwellian distribution, for which the anisotropy parameter can be simplified to temperature anisotropy (T⊥/T∥-1) independent of specific energy of particles. In this paper, we studied the proton anisotropy related to EMIC waves using the Van Allen Probes observations in the inner magnetosphere. First, we found that the real velocity distribution of protons is usually not expressed with a simple bi-Maxwellian distribution. Also, we calculated the anisotropy parameter using the exact formula defined by Kennel and Petschek [1966] and investigated the linear instability criterion of them. We found that, for majority of the EMIC wave events, the threshold anisotropy condition for proton cyclotron instability is satisfied in the expected range of resonant energy. We further determined the parallel plasma beta and its inverse relationship with the anisotropy parameter. The inverse relationship exists both during the EMIC wave times and non-EMIC wave times, but with different slopes. Based on this result, we demonstrate that the parallel plasma beta can be a critical factor that determines occurrence of EMIC waves.

Determination of astaxanthin in Haematococcus pluvialis by first-order derivative spectrophotometry.

PubMed

Liu, Xiao Juan; Juan, Liu Xiao; Wu, Ying Hua; Hua, Wu Ying; Zhao, Li Chao; Chao, Zhao Li; Xiao, Su Yao; Yao, Xiao Su; Zhou, Ai Mei; Mei, Zhou Ai; Liu, Xin; Xin, Liu

2011-01-01

A highly selective, convenient, and precise method, first-order derivative spectrophotometry, was applied for the determination of astaxanthin in Haematococcus pluvialis. Ethyl acetate and ethanol (1:1, v/v) were found to be the best extraction solvent tested due to their high efficiency and low toxicity compared with nine other organic solvents. Astaxanthin coexisting with chlorophyll and beta-carotene was analyzed by first-order derivative spectrophotometry in order to optimize the conditions for the determination of astaxanthin. The results show that when detected at 432 nm, the interfering substances could be eliminated. The dynamic linear range was 2.0-8.0 microg/mL, with a correlation coefficient of 0.9916. The detection threshold was 0.41 microg/mL. The RSD for the determination of astaxanthin was in the range of 0.01-0.06%; the results of recovery test were 98.1-108.0%. The statistical analysis between first-order derivative spectrophotometry and HPLC by T-testing did not exceed their critical values, revealing no significant differences between these two methods. It was proved that first-order derivative spectrophotometry is a rapid and convenient method for the determination of astaxanthin in H. pluvialis that can eliminate the negative effect resulting from the coexistence of astaxanthin with chlorophyll and beta-carotene.

Expression of S100 beta in sensory and secretory cells of the vertebrate inner ear

NASA Technical Reports Server (NTRS)

Fermin, C. D.; Martin, D. S.

1995-01-01

We evaluated anti-S100 beta expression in the chick (Gallus domesticus) inner ear and determined that: 1) the monomer anti-S100 beta is expressed differentially in the vestibular and auditory perikarya; 2) expression of S100 beta in the afferent nerve terminals is time-related to synapse and myelin formation; 3) the expression of the dimer anti-S100 alpha alpha beta beta and monomer anti-S100 beta overlaps in most inner ear cell types. Most S100 alpha alpha beta beta positive cells express S100 beta, but S100 beta positive cells do not always express S100 alpha alpha beta beta. 4) the expression of S100 beta is diffused over the perikaryal cytoplasm and nuclei of the acoustic ganglia but is concentrated over the nuclei of the vestibular perikarya. 6) S100 beta is expressed in secretory cells, and it is co-localized with GABA in sensory cells. 7) Color thresholding objective quantitation indicates that the amount of S100 beta was higher (mean 22, SD +/- 4) at E19 than at E9 (mean 34, SD +/- 3) in afferent axons. 8) Moreover, S100 beta was unchanged between E11-E19 in the perikaryal cytoplasm, but did change over the nuclei. At E9, 74%, and at E21, 5% of vestibular perikarya were positive. The data suggest that S100 beta may be physically associated with neuronal and ionic controlling cells of the vertebrate inner ear, where it could provide a dual ionic and neurotrophic modulatory function.

Subliminal stimuli modulate somatosensory perception rhythmically and provide evidence for discrete perception.

PubMed

Baumgarten, Thomas J; Königs, Sara; Schnitzler, Alfons; Lange, Joachim

2017-03-09

Despite being experienced as continuous, there is an ongoing debate if perception is an intrinsically discrete process, with incoming sensory information treated as a succession of single perceptual cycles. Here, we provide causal evidence that somatosensory perception is composed of discrete perceptual cycles. We used in humans an electrotactile temporal discrimination task preceded by a subliminal (i.e., below perceptual threshold) stimulus. Although not consciously perceived, subliminal stimuli are known to elicit neuronal activity in early sensory areas and modulate the phase of ongoing neuronal oscillations. We hypothesized that the subliminal stimulus indirectly, but systematically modulates the ongoing oscillatory phase in S1, thereby rhythmically shaping perception. The present results confirm that, without being consciously perceived, the subliminal stimulus critically influenced perception in the discrimination task. Importantly, perception was modulated rhythmically, in cycles corresponding to the beta-band (13-18 Hz). This can be compellingly explained by a model of discrete perceptual cycles.

Ecosystem thresholds, tipping points, and critical transitions

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

Munson, Seth M.; Reed, Sasha C.; Peñuelas, Josep

Terrestrial ecosystems in a time of change: thresholds, tipping points, and critical transitions; an organized session at the American Geophysical Union Fall Meeting in New Orleans, Louisiana, USA, December 2017

The majorana experiment

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

Rielage, Keith R; Elliott, Steven R; Boswell, Melissa

2010-12-13

The MAJORANA Collaboration is assembling an array of HPGe detectors to search for neutrinoless double-beta decay in {sup 76}Ge. Initially, MAJORANA aims to construct a prototype module to demonstrate the potential of a future 1-tonne experiment. The design and potential reach of this prototype DEMONSTRATOR module are presented. Our proposed method uses the well-established technique of searching for neutrinoless double-beta decay in high purity Ge-diode radiation detectors that play both roles of source and detector. The use of P-PC Ge detectors present advances in background rejection and a Significantly lower energy threshold than conventional Ge detector technologies. The lower energymore » threshold opens up a broader and exciting physics program including searches for dark matter and axions concurrent with the double-beta decay search. The DEMONSTRATOR should establish that the backgrounds are low enough to justify scaling to tonne-scale experiment, probe the neutrino effective mass region above 100 meV, and search the low energy region with a sensitivity to dark matter. The DEMONSTRATOR will be sited at the 4850-ft level (4200 m.w.e) of the Sanford Underground Laboratory at Homestake and preparations for construction are currently underway.« less

An Intrinsic Role of Beta Oscillations in Memory for Time Estimation.

PubMed

Wiener, Martin; Parikh, Alomi; Krakow, Arielle; Coslett, H Branch

2018-05-22

The neural mechanisms underlying time perception are of vital importance to a comprehensive understanding of behavior and cognition. Recent work has suggested a supramodal role for beta oscillations in measuring temporal intervals. However, the precise function of beta oscillations and whether their manipulation alters timing has yet to be determined. To accomplish this, we first re-analyzed two, separate EEG datasets and demonstrate that beta oscillations are associated with the retention and comparison of a memory standard for duration. We next conducted a study of 20 human participants using transcranial alternating current stimulation (tACS), over frontocentral cortex, at alpha and beta frequencies, during a visual temporal bisection task, finding that beta stimulation exclusively shifts the perception of time such that stimuli are reported as longer in duration. Finally, we decomposed trialwise choice data with a drift diffusion model of timing, revealing that the shift in timing is caused by a change in the starting point of accumulation, rather than the drift rate or threshold. Our results provide evidence for the intrinsic involvement of beta oscillations in the perception of time, and point to a specific role for beta oscillations in the encoding and retention of memory for temporal intervals.

Extended infusion of beta-lactam antibiotics: optimizing therapy in critically-ill patients in the era of antimicrobial resistance.

PubMed

Rizk, Nesrine A; Kanafani, Zeina A; Tabaja, Hussam Z; Kanj, Souha S

2017-07-01

Beta-lactams are at the cornerstone of therapy in critical care settings, but their clinical efficacy is challenged by the rise in bacterial resistance. Infections with multi-drug resistant organisms are frequent in intensive care units, posing significant therapeutic challenges. The problem is compounded by a dearth in the development of new antibiotics. In addition, critically-ill patients have unique physiologic characteristics that alter the drugs pharmacokinetics and pharmacodynamics. Areas covered: The prolonged infusion of antibiotics (extended infusion [EI] and continuous infusion [CI]) has been the focus of research in the last decade. As beta-lactams have time-dependent killing characteristics that are altered in critically-ill patients, prolonged infusion is an attractive approach to maximize their drug delivery and efficacy. Several studies have compared traditional dosing to EI/CI of beta-lactams with regard to clinical efficacy. Clinical data are primarily composed of retrospective studies and some randomized controlled trials. Several reports show promising results. Expert commentary: Reviewing the currently available evidence, we conclude that EI/CI is probably beneficial in the treatment of critically-ill patients in whom an organism has been identified, particularly those with respiratory infections. Further studies are needed to evaluate the efficacy of EI/CI in the management of infections with resistant organisms.

Matrix-calibrated LC-MS/MS quantitation and sensory evaluation of oak Ellagitannins and their transformation products in red wines.

PubMed

Stark, Timo; Wollmann, Nadine; Wenker, Kerstin; Lösch, Sofie; Glabasnia, Arne; Hofmann, Thomas

2010-05-26

Aimed at investigating the concentrations and taste contribution of the oak-derived ellagitannins castalagin and vescalagin as well as their transformation products acutissimin A/B, epiacutissimin A/B, and beta-1-O-ethylvescalagin in red wine, a highly sensitive and accurate quantification method was developed on the basis of LC-MS/MS-MRM analysis with matrix calibration. Method validation showed good recovery rates ranging from 102.4 +/- 5.9% (vescalagin) to 113.7 +/- 15.2% (epiacutissimin A). In oak-matured wines, castalagin was found as the predominant ellagitannin, followed by beta-1-O-ethylvescalagin, whereas the flavano-C-ellagitannins (epi)acutissimin A/B were present in significantly lower amounts. In contrast to the high threshold concentration levels (600-1000 micromol/L) and the puckering astringent orosensation induced by flavan-3-ols, all of the ellagitannin derivatives were found to induce a smooth and velvety astringent oral sensation at rather low threshold concentrations ranging from 0.9 to 2.8 micromol/L. Dose/activity considerations demonstrated that, among all the ellagitannins investigated, castalagin exclusively exceeded its threshold concentration in various oak-matured wine samples.

Critical fluctuations and the rates of interstate switching near the excitation threshold of a quantum parametric oscillator.

PubMed

Lin, Z R; Nakamura, Y; Dykman, M I

2015-08-01

We study the dynamics of a nonlinear oscillator near the critical point where period-two vibrations are first excited with the increasing amplitude of parametric driving. Above the threshold, quantum fluctuations induce transitions between the period-two states over the quasienergy barrier. We find the effective quantum activation energies for such transitions and their scaling with the difference of the driving amplitude from its critical value. We also find the scaling of the fluctuation correlation time with the quantum noise parameters in the critical region near the threshold. The results are extended to oscillators with nonlinear friction.

Critical, sustainable and threshold fluxes for membrane filtration with water industry applications.

PubMed

Field, Robert W; Pearce, Graeme K

2011-05-11

Critical flux theory evolved as a description of the upper bound in the operating envelope for controlled steady state environments such as cross-flow systems. However, in the application of UF membranes in the water industry, dead-end (direct-flow) designs are used. Direct-flow is a pseudo steady state operation with different fouling characteristics to cross-flow, and thus the critical flux concept has limited applicability. After a review of recent usage of the critical flux theory, an alternative concept for providing design guidelines for direct-flow systems namely that of the threshold flux is introduced. The concept of threshold flux can also be applicable to cross-flow systems. In more general terms the threshold flux can be taken to be the flux that divides a low fouling region from a high fouling region. This may be linked both to the critical flux concept and to the concept of a sustainable flux. The sustainable flux is the one at which a modest degree of fouling occurs, providing a compromise between capital expenditure (which is reduced by using high flux) and operating costs (which are reduced by restricting the fouling rate). Whilst the threshold flux can potentially be linked to physical phenomena alone, the sustainable flux also depends upon economic factors and is thus of a different nature to the critical and threshold fluxes. This distinction will be illustrated using some MBR data. Additionally the utility of the concept of a threshold flux will be illustrated using pilot plant data obtained for UF treatment of four sources of water. Copyright © 2011 Elsevier B.V. All rights reserved.

Sources of stress and psychological morbidity among undergraduate physiotherapy students.

PubMed

Walsh, J M; Feeney, C; Hussey, J; Donnellan, C

2010-09-01

Professional education can be a stressful experience for some individuals, and may impact negatively on emotional well-being and academic performance. Psychological morbidity and associated sources of stress have not been investigated extensively in physiotherapy students. This study explored sources of stress, psychological morbidity and possible associations between these variables in undergraduate physiotherapy students. A questionnaire-based survey. The Undergraduate Sources of Stress Questionnaire was used to identify sources of stress, and the General Health Questionnaire-12 (GHQ-12) was used to rate the prevalence of psychological morbidity, using a conservative GHQ threshold of 3 to 4 to determine probable 'cases'. Uni- and multivariate tests of correlation were used to analyse the data. An Irish educational institution. One hundred and twenty-five physiotherapy undergraduate students. More than one-quarter of all students (27%) scored above the GHQ threshold, indicating probable psychological morbidity. This is higher than the level of psychological morbidity reported by the general population. Regression analysis showed that academic (beta=0.31, P<0.001) and personal (beta=0.50, P<0.001) sources of stress subscales were significant coefficients, explaining 48% of the variance in psychological morbidity after controlling for part-time employment and hours spent studying. Individual significant items from these subscales were stressful events (beta=0.24, P=0.004), mood (beta=0.43, P< or =0.001) and overall level of stress (beta=0.35, P< or =0.001). The results highlighted the emotional vulnerability of a significant proportion of physiotherapy students, with academic and personal issues being the greatest concern. While personal causes of stress such as stressful events and mood are more difficult to control, manipulation of curricular factors may have positive effects on academic sources of stress. Copyright 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Information Technology Portfolio Management Proof of Concept: Modern Portfolio Theory With KVA and ROI Analysis

DTIC Science & Technology

2010-09-01

approach” that provides analysis for “program managers to attain the right knowledge [e.g., portfolio values] at critical junctures so they can make...portfolio, it is critical to create a credible beta (β) for the presumed “market volatility” of the IT asset class. The KVA methodology may be used...for this critical task. Establishing a beta (β) for DoD wide IT portfolio management uses the work conducted at the Naval Postgraduate School (NPS

Increased vitamin plasma levels in Swedish military personnel treated with nutrients prior to automatic weapon training

PubMed Central

Le Prell, C. G.; Johnson, A.-C.; Lindblad, A.-C.; Skjönsberg, Å.; Ulfendahl, M.; Guire, K.; Green, G. E.; Campbell, K. C. M.; Miller, J. M.

2013-01-01

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. The development of novel therapeutic agents to reduce NIHL will potentially benefit multiple very large noise-exposed populations. Oxidative stress has been identified as a significant contributor to noise-induced sensory cell death and noise-induced hearing loss, and several antioxidant strategies have now been suggested for potential translation to human subjects. One such strategy is a combination of beta-carotene, vitamins C and E, and magnesium, which has shown promise for protection against NIHL in rodent models, and is being evaluated in a series of international human clinical trials using temporary (military gunfire, audio player use) and permanent (stamping factory, military airbase) threshold shift models (NCT00808470). The noise exposures used in the recently completed Swedish military gunfire study described in this report did not, on average, result in measurable changes in auditory function using conventional pure-tone thresholds and distortion product otoacoustic emission (DPOAE) amplitudes as metrics. However, analysis of the plasma samples confirmed significant elevations in the bloodstream 2 hours after oral consumption of active clinical supplies, indicating the dose is realistic. The plasma outcomes are encouraging, but clinical acceptance of any novel therapeutic critically depends on demonstration that the agent reduces noise-induced threshold shift in randomized, placebo-controlled, prospective human clinical trials. Although this noise insult did not induce hearing loss, the trial design and study protocol can be applied to other populations exposed to different noise insults. PMID:22122960

High fat programming of beta cell compensation, exhaustion, death and dysfunction.

PubMed

Cerf, Marlon E

2015-03-01

Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co-presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Beta-catenin regulates vitamin C biosynthesis and cell survival in murine liver.

PubMed

Nejak-Bowen, Kari N; Zeng, Gang; Tan, Xinping; Cieply, Benjamin; Monga, Satdarshan P

2009-10-09

Because the Wnt/beta-catenin pathway plays multiple roles in liver pathobiology, it is critical to identify gene targets that mediate such diverse effects. Here we report a novel role of beta-catenin in controlling ascorbic acid biosynthesis in murine liver through regulation of expression of regucalcin or senescence marker protein 30 and L-gulonolactone oxidase. Reverse transcription-PCR, Western blotting, and immunohistochemistry demonstrate decreased regucalcin expression in beta-catenin-null livers and greater expression in beta-catenin overexpressing transgenic livers, HepG2 hepatoma cells (contain constitutively active beta-catenin), regenerating livers, and in hepatocellular cancer tissues that exhibit beta-catenin activation. Interestingly, coprecipitation and immunofluorescence studies also demonstrate an association of beta-catenin and regucalcin. Luciferase reporter and chromatin immunoprecipitation assays verified a functional TCF-4-binding site located between -163 and -157 (CTTTGCA) on the regucalcin promoter to be critical for regulation by beta-catenin. Significantly lower serum ascorbate levels were observed in beta-catenin knock-out mice secondary to decreased expression of regucalcin and also of L-gulonolactone oxidase, the penultimate and last (also rate-limiting) steps in the synthesis of ascorbic acid, respectively. These mice also show enhanced basal hepatocyte apoptosis. To test if ascorbate deficiency secondary to beta-catenin loss and regucalcin decrease was contributing to apoptosis, beta-catenin-null hepatocytes or regucalcin small interfering RNA-transfected HepG2 cells were cultured, which exhibited significant apoptosis that was alleviated by the addition of ascorbic acid. Thus, through regucalcin and L-gulonolactone oxidase expression, beta-catenin regulates vitamin C biosynthesis in murine liver, which in turn may be one of the mechanisms contributing to the role of beta-catenin in cell survival.

Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)-mediated signal transduction pathway: role of GSK-3beta in myocardial protection against ischemia/reperfusion injury.

PubMed

Miura, Tetsuji; Nishihara, Masahiro; Miki, Takayuki

2009-02-01

Although reperfusion is required to salvage ischemic myocardium from necrosis, reperfusion per se induces myocardial necrosis. In this "lethal reperfusion injury", opening of the mitochondrial permeability transition pore (mPTP) upon reperfusion is crucially involved. The mPTP primarily consists of adenine nucleotide translocator (ANT) and voltage-dependent anion channel, and its opening is triggered by binding of cyclophilin-D (CyP-D) to ANT, which increases Ca(2+) sensitivity of the mPTP. Recent studies have shown that inactivation of glycogen synthase kinase-3beta (GSK-3beta) suppresses mPTP opening and protects cardiomyocytes. Multiple intracellular signals relevant to cardiomyocyte protection converge to GSK-3beta and inactivate this kinase by phosphorylation. Although the effect of GSK-3beta phosphorylation on mPTP structure and function remains unclear, suppression of ANT-CyP-D interaction by binding of phospho-GSK-3beta to ANT and reduction in GSK-3beta-mediated phosphorylation of p53 may contribute to elevation of the threshold for mPTP opening. Furthermore, a significant inverse correlation was observed between level of phospho-GSK-3beta at the time of reperfusion and the extent of myocardium infarction in heart. Together with the infarct size-limiting effect of GSK-3beta inhibitors, this finding indicates that phospho-GSK-3beta is a determinant of myocardial tolerance against reperfusion-induced necrosis. Thus, GSK-3beta appears to be a target of novel therapy for cardioprotection upon reperfusion.

The final results of the Mi-Beta Cryogenic Experiment towards the CUORICINO Experiment

NASA Astrophysics Data System (ADS)

Pirro, S.; Arnaboldi, C.; Brofferio, C.; Bucci, C.; Capelli, S.; Cremonesi, O.; Fiorini, E.; Giuliani, A.; McDonald, R. J.; Nucciotti, A.; Pavan, M.; Pedretti, M.; Pessina, G.; Pobes, C.; Previtali, E.; Sisti, M.; Vanzini, M.; Zanotti, L.

2002-02-01

We present the final results on neutrinoless Double Beta Decay (DBD) of 130Te obtained with an array of 20 cryogenic detectors. The Mi-Beta Experiment is operating since 3 years and was upgraded in March 2001. The background in the DBD energy region was reduced thanks to a new Roman lead shield framed inside the dilution unit and a neutron shield mounted outside the cryostat. We also improved the energy threshold using a cold electronic stage inside the cryostat. The new set-up represents also a good test for the CUORICINO Experiment. CUORICINO will start by the beginning of 2002 and will consist of 56 Tellurium Oxide Crystal with an overall bolometric mass of 42 kg. .

{beta}-Catenin stabilization imparts crypt progenitor phenotype to hyperproliferating colonic epithelia

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

Sellin, Joseph H.; Wang Yu; Singh, Pomila

2009-01-01

Utilizing the Citrobacter rodentium (CR)-induced transmissible murine colonic hyperplasia (TMCH) model, we provide mechanistic basis of changes in {beta}-catenin/APC/CKI{epsilon} leading to progression and/or regression of hyperplasia in vivo. In response to CR-induced TMCH, crypt lengths increased significantly between days 6-27 post-infection, followed by a steep decline by day 34. {beta}-Cat{sup 45}/total {beta}-catenin were elevated on day 1 post-infection, preceding changes in crypt length, and persisted for 27 days before declining by day 34. Importantly, cellular CKI{epsilon} and {beta}-catenin co-immunoprecipitated and exhibited remarkable parallel changes in kinetics during hyperplasia/regression phases. {beta}-catenin, phosphorylated at Ser33,37 and Thr41 ({beta}-cat{sup 33,37/41}), was low tillmore » day 12, followed by gradual increase until day 27 before declining by day 34. GSK-3{beta} exhibited significant Ser{sup 9}-phosphorylation/inactivation at days 6-12 with partial recovery at days 27-34. Wild type (wt) APC (p312) levels increased at day 6 with transient proteolysis/truncation to p130 form between days 12 and 15; p312 reappeared by day 19 and returned to baseline by day 34. The kinetics of {beta}-Cat{sup 45}/{beta}-catenin nuclear accumulation and acetylation (Ac-{beta}-Cat{sup Lys49}) from days 6 to 27, followed by loss of phosphorylation/acetylation by day 34 was almost identical; Tcf-4 co-immunoprecipitated with {beta}-Cat{sup 45}/{beta}-catenin and localized immunohistochemically to {beta}-Cat{sup 41/45}-positive regions leading to elevated cyclin D1 expression, during the hyperproliferative, but not regression phases of TMCH. CKI{epsilon} mediated phosphorylation of {beta}-Cat{sup 45}, resulting in stabilization/nuclear translocation of {beta}-Cat{sup 45} may be critical for maintaining proliferation at days 6-27. Reversal of GSK-3{beta} phosphorylation and APC changes may be equally critical during the regression phase from days 27 to 34.« less

Intermittent fasting preserves beta-cell mass in obesity-induced diabetes via the autophagy-lysosome pathway.

PubMed

Liu, Haiyan; Javaheri, Ali; Godar, Rebecca J; Murphy, John; Ma, Xiucui; Rohatgi, Nidhi; Mahadevan, Jana; Hyrc, Krzysztof; Saftig, Paul; Marshall, Connie; McDaniel, Michael L; Remedi, Maria S; Razani, Babak; Urano, Fumihiko; Diwan, Abhinav

2017-01-01

Obesity-induced diabetes is characterized by hyperglycemia, insulin resistance, and progressive beta cell failure. In islets of mice with obesity-induced diabetes, we observe increased beta cell death and impaired autophagic flux. We hypothesized that intermittent fasting, a clinically sustainable therapeutic strategy, stimulates autophagic flux to ameliorate obesity-induced diabetes. Our data show that despite continued high-fat intake, intermittent fasting restores autophagic flux in islets and improves glucose tolerance by enhancing glucose-stimulated insulin secretion, beta cell survival, and nuclear expression of NEUROG3, a marker of pancreatic regeneration. In contrast, intermittent fasting does not rescue beta-cell death or induce NEUROG3 expression in obese mice with lysosomal dysfunction secondary to deficiency of the lysosomal membrane protein, LAMP2 or haplo-insufficiency of BECN1/Beclin 1, a protein critical for autophagosome formation. Moreover, intermittent fasting is sufficient to provoke beta cell death in nonobese lamp2 null mice, attesting to a critical role for lysosome function in beta cell homeostasis under fasting conditions. Beta cells in intermittently-fasted LAMP2- or BECN1-deficient mice exhibit markers of autophagic failure with accumulation of damaged mitochondria and upregulation of oxidative stress. Thus, intermittent fasting preserves organelle quality via the autophagy-lysosome pathway to enhance beta cell survival and stimulates markers of regeneration in obesity-induced diabetes.

Fluorescence microplate readers as an alternative to flow injection analysis for determination of wort beta-glucan

USDA-ARS?s Scientific Manuscript database

Wort beta-glucan concentration is a critical malting quality parameter used to identify and avoid potential brewhouse filtration problems. ASBC method Wort-18 is widely used in malt analysis laboratories and brewhouses to measure wort beta-glucan levels. However, the chemistry underlying the method...

Fatigue Crack Growth Threshold Testing of Metallic Rotorcraft Materials

NASA Technical Reports Server (NTRS)

Newman, John A.; James, Mark A.; Johnson, William M.; Le, Dy D.

2008-01-01

Results are presented for a program to determine the near-threshold fatigue crack growth behavior appropriate for metallic rotorcraft alloys. Four alloys, all commonly used in the manufacture of rotorcraft, were selected for study: Aluminum alloy 7050, 4340 steel, AZ91E Magnesium, and Titanium alloy Ti-6Al-4V (beta-STOA). The Federal Aviation Administration (FAA) sponsored this research to advance efforts to incorporate damage tolerance design and analysis as requirements for rotorcraft certification. Rotorcraft components are subjected to high cycle fatigue and are typically subjected to higher stresses and more stress cycles per flight hour than fixed-wing aircraft components. Fatigue lives of rotorcraft components are generally spent initiating small fatigue cracks that propagate slowly under near-threshold cracktip loading conditions. For these components, the fatigue life is very sensitive to the near-threshold characteristics of the material.

Critical ratios of beluga whales (Delphinapterus leucas) and masked signal duration.

PubMed

Erbe, Christine

2008-10-01

This article examines the masking of a complex beluga vocalization by natural and anthropogenic noise. The call consisted of six 150 ms pulses exhibiting spectral peaks between 800 Hz and 8 kHz. Comparing the spectra and spectrograms of the call and noises at detection threshold showed that the animal did not hear the entire call at threshold. It only heard parts of the call in frequency and time. From the masked hearing thresholds in broadband continuous noises, critical ratios were computed. Fletcher critical bands were narrower than either 15 or 111 of an octave at the low frequencies of the call (<2 kHz), depending on which frequency the animal cued on. From the masked hearing thresholds in intermittent noises, the audible signal duration at detection threshold was computed. The intermittent noises differed in gap length, gap number, and masking, but the total audible signal duration at threshold was the same: 660 ms. This observation supports a multiple-looks model. The two amplitude modulated noises exhibited weaker masking than the unmodulated noises hinting at a comodulation masking release.

Suitability of macrophage inflammatory protein-1beta production by THP-1 cells in differentiating skin sensitizers from irritant chemicals.

PubMed

Lim, Yeon-Mi; Moon, Seong-Joon; An, Su-Sun; Lee, Soo-Jin; Kim, Seo-Young; Chang, Ih-Seop; Park, Kui-Lea; Kim, Hyoung-Ah; Heo, Yong

2008-04-01

Worldwide restrictions in animal use for research have driven efforts to develop alternative methods. The study aimed to test the efficacy of the macrophage inflammatory protein-1beta (MIP-1beta) assay for testing chemicals' skin-sensitizing capacity. The assay was performed using 9 chemicals judged to be sensitizing and 7 non-sensitizing by the standard in vivo assays. THP-1 cells were cultured in the presence or absence of 4 doses, 0.01x, 0.1x, 0.5x, or 1x IC(50) (50% inhibitory concentration for THP-1 cell proliferation) of these chemicals for 24 hr, and the MIP-1beta level in the supernatants was determined. Skin sensitization by the test chemicals was determined by MIP-1beta production rates. The MIP-1beta production rate was expressed as the relative increase in MIP-1beta production in response to chemical treatment compared with vehicle treatment. When the threshold MIP-1beta production rate used was 100% or 105% of dimethyl sulfoxide, all the sensitizing chemicals tested (dinitrochlorobenzene, hexyl cinnamic aldehyde, eugenol, hydroquinone, dinitrofluorobenzene, benzocaine, nickel, chromium, and 5-chloro-2-methyl-4-isothiazolin-3-one) were positive, and all the non-sensitizing chemicals (methyl salicylate, benzalkonium chloride, lactic acid, isopropanol, and salicylic acid), with the exception of sodium lauryl sulfate, were negative for MIP-1beta production. These results indicate that MIP-1beta could be a biomarker for classification of chemicals as sensitizers or non-sensitizers.

Sequence of Changes in Maize Responding to Soil Water Deficit and Related Critical Thresholds

PubMed Central

Ma, Xueyan; He, Qijin; Zhou, Guangsheng

2018-01-01

The sequence of changes in crop responding to soil water deficit and related critical thresholds are essential for better drought damage classification and drought monitoring indicators. This study was aimed to investigate the critical thresholds of maize growth and physiological characteristics responding to changing soil water and to reveal the sequence of changes in maize responding to soil water deficit both in seedling and jointing stages based on 2-year’s maize field experiment responding to six initial soil water statuses conducted in 2013 and 2014. Normal distribution tolerance limits were newly adopted to identify critical thresholds of maize growth and physiological characteristics to a wide range of soil water status. The results showed that in both stages maize growth characteristics related to plant water status [stem moisture content (SMC) and leaf moisture content (LMC)], leaf gas exchange [net photosynthetic rate (Pn), transpiration rate (Tr), and stomatal conductance (Gs)], and leaf area were sensitive to soil water deficit, while biomass-related characteristics were less sensitive. Under the concurrent weather conditions and agronomic managements, the critical soil water thresholds in terms of relative soil moisture of 0–30 cm depth (RSM) of maize SMC, LMC, net Pn, Tr, Gs, and leaf area were 72, 65, 62, 60, 58, and 46%, respectively, in seedling stage, and 64, 64, 51, 53, 48, and 46%, respectively, in jointing stage. It indicated that there is a sequence of changes in maize responding to soil water deficit, i.e., their response sequences as soil water deficit intensified: SMC ≥ LMC > leaf gas exchange > leaf area in both stages. This sequence of changes in maize responding to soil water deficit and related critical thresholds may be better indicators of damage classification and drought monitoring. PMID:29765381

Fast non-genomic effects of progesterone-derived neurosteroids on nociceptive thresholds and pain symptoms.

PubMed

Charlet, Alexandre; Lasbennes, François; Darbon, Pascal; Poisbeau, Pierrick

2008-10-31

Fast Inhibitory controls mediated by glycine (GlyRs) and GABAA receptors (GABAARs) play an important role to prevent the apparition of pathological pain symptoms of allodynia and hyperalgesia. The use of positive allosteric modulators of these receptors, specifically expressed in the spinal cord, may represent an interesting strategy to limit or block pain expression. In this study, we have used stereoisomers of progesterone metabolites, acting only via non-genomic effects, in order to evaluate the contribution of GlyRs and GABAARs for the reduction of mechanical and thermal heat hypernociception. We show that 3alpha neurosteroids were particularly efficient to elevate nociceptive thresholds in naive animal. It also reduced mechanical allodynia and thermal heat hyperalgesia in the carrageenan model of inflammatory pain. This effect is likely to be mediated by GABAA receptors since 3beta isomer was inefficient. More interestingly, 3alpha5beta neurosteroid was only efficient on mechanical allodynia while having no effect on thermal heat hyperalgesia. We characterized these paradoxical effects of 3alpha5beta neurosteroid using the strychnine and bicuculline models of allodynia. We clearly show that 3alpha5beta neurosteroid exerts an antinociceptive effect via a positive allosteric modulation of GABAARs but, at the same time, is pronociceptive by reducing GlyR function. This illustrates the importance of the inhibitory amino acid receptor channels and their allosteric modulators in spinal pain processing. Moreover, our results indicate that neurosteroids, which are synthesized in the dorsal horn of the spinal cord and have limited side effects, may be of significant interest in order to treat pathological pain symptoms.

A test of critical thresholds and their indicators in a desertification-prone ecosystem: more resilience than we thought

USGS Publications Warehouse

Bestelmeyer, Brandon T.; Duniway, Michael C.; James, Darren K.; Burkett, Laura M.; Havstad, Kris M.

2013-01-01

Theoretical models predict that drylands can cross critical thresholds, but experimental manipulations to evaluate them are non-existent. We used a long-term (13-year) pulse-perturbation experiment featuring heavy grazing and shrub removal to determine if critical thresholds and their determinants can be demonstrated in Chihuahuan Desert grasslands. We asked if cover values or patch-size metrics could predict vegetation recovery, supporting their use as early-warning indicators. We found that season of grazing, but not the presence of competing shrubs, mediated the severity of grazing impacts on dominant grasses. Recovery occurred at the same rate irrespective of grazing history, suggesting that critical thresholds were not crossed, even at low cover levels. Grass cover, but not patch size metrics, predicted variation in recovery rates. Some transition-prone ecosystems are surprisingly resilient; management of grazing impacts and simple cover measurements can be used to avert undesired transitions and initiate restoration.

Critical thresholds and recovery of Chihuahuan Desert grasslands: Insights from long-term data

USDA-ARS?s Scientific Manuscript database

Background/Question/Methods: Desertification and other harmful state transitions in drylands are expected to accelerate with global change. Ecologists are called upon to devise methods to anticipate critical thresholds and promote recovery of desired states. As in other drylands, transitions in sem...

Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.

PubMed

Kanasaki, Keizo; Kanda, Yoshiko; Palmsten, Kristin; Tanjore, Harikrishna; Lee, Soo Bong; Lebleu, Valerie S; Gattone, Vincent H; Kalluri, Raghu

2008-01-15

The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.

Using support vector machine to predict beta- and gamma-turns in proteins.

PubMed

Hu, Xiuzhen; Li, Qianzhong

2008-09-01

By using the composite vector with increment of diversity, position conservation scoring function, and predictive secondary structures to express the information of sequence, a support vector machine (SVM) algorithm for predicting beta- and gamma-turns in the proteins is proposed. The 426 and 320 nonhomologous protein chains described by Guruprasad and Rajkumar (Guruprasad and Rajkumar J. Biosci 2000, 25,143) are used for training and testing the predictive model of the beta- and gamma-turns, respectively. The overall prediction accuracy and the Matthews correlation coefficient in 7-fold cross-validation are 79.8% and 0.47, respectively, for the beta-turns. The overall prediction accuracy in 5-fold cross-validation is 61.0% for the gamma-turns. These results are significantly higher than the other algorithms in the prediction of beta- and gamma-turns using the same datasets. In addition, the 547 and 823 nonhomologous protein chains described by Fuchs and Alix (Fuchs and Alix Proteins: Struct Funct Bioinform 2005, 59, 828) are used for training and testing the predictive model of the beta- and gamma-turns, and better results are obtained. This algorithm may be helpful to improve the performance of protein turns' prediction. To ensure the ability of the SVM method to correctly classify beta-turn and non-beta-turn (gamma-turn and non-gamma-turn), the receiver operating characteristic threshold independent measure curves are provided. (c) 2008 Wiley Periodicals, Inc.

A designed beta-hairpin forming peptide undergoes a consecutive stepwise process for self-assembly into nanofibrils.

PubMed

Wang, Chong; Sha, Yinlin

2010-04-01

We used a de novo designed, beta-hairpin forming T1 peptide as a model to investigate the kinetics of peptide fibrogenesis by a combination of light scattering (LS), circular dichroism (CD), fluorescence, and atomic force microscopy (AFM). The results demonstrate that the T1 fibrogenesis undergoes a consecutive stepwise process, with a high degree of cooperation, presenting sigmoidal time-courses of the peptide aggregation, the subsequent conformational conversion of the backbone, and the peptide sidechains' rearrangement. We suggest that the conformational conversion was initiated after the peptide aggregates reach a dimensional size threshold, which could be a key step in the formation of beta-structural nuclei that catalyze the subsequent reactions. Furthermore, besides triggering the peptide aggregation, the interactions between the peptide sidechains predominately facilitate the regular alignment of the peptide molecules and the formation of a well-defined suprastructure. This work provides an insight of the hierarchical self-assembly of beta-hairpin forming peptides. It is helpful for designing beta-structural peptides for self-assembly into nanowires, which would have potential applications in the construction of nano-materials.

The effects of aromatic amino acid derivatives on the excitability of an identifiable giant neurone of the African giant snail (Achatina fulica Férussac).

PubMed Central

Takeuchi, H.; Tamura, H.

1980-01-01

1 The effects of derivatives of aromatic amino acids on the excitability of an identifiable giant neurone (TAN, tonically autoactive neurone) of the African giant snail (Achatina fulica Férussac) were examined. 2 The following substances had marked inhibitory effects on TAN using bath application: N-beta-phenylpropionyl-L-Tyr and N-beta-phenylpropionyl-L-Trp (critical concentration, 3 x 10(-7) M), N-beta-phenylpropionyl-L-Phe, N-cinnamoyl-DL-Trp and N-phenoxyacetyl-L-Trp (critical concentration, 10(-5) to 3 x 10(-5) M). However, N-beta-phenylpropionyl-D-Tyr and N-beta-phenylpropionyl tyramine had no effect. 3 Microdrop (150 micrometers in diameter) application of N-beta-phenylpropionyl-L-Tyr or N-beta-phenylpropionyl-l-trp containing about 100 pg resulted in marked inhibitory effects on TAN. The effect was observed in Ca2+-free, Mg2+-rich (24 mM) solution. Substitution of Cl- by acetate did not alter the response. This indicates that the two substances act directly on the TAN membrane and not via synaptic influences, and that the inhibition produced by the two substances is not due to the permeability increase of the TAN membrane to Cl-. PMID:7378654

Subliminal stimuli modulate somatosensory perception rhythmically and provide evidence for discrete perception

PubMed Central

Baumgarten, Thomas J.; Königs, Sara; Schnitzler, Alfons; Lange, Joachim

2017-01-01

Despite being experienced as continuous, there is an ongoing debate if perception is an intrinsically discrete process, with incoming sensory information treated as a succession of single perceptual cycles. Here, we provide causal evidence that somatosensory perception is composed of discrete perceptual cycles. We used in humans an electrotactile temporal discrimination task preceded by a subliminal (i.e., below perceptual threshold) stimulus. Although not consciously perceived, subliminal stimuli are known to elicit neuronal activity in early sensory areas and modulate the phase of ongoing neuronal oscillations. We hypothesized that the subliminal stimulus indirectly, but systematically modulates the ongoing oscillatory phase in S1, thereby rhythmically shaping perception. The present results confirm that, without being consciously perceived, the subliminal stimulus critically influenced perception in the discrimination task. Importantly, perception was modulated rhythmically, in cycles corresponding to the beta-band (13–18 Hz). This can be compellingly explained by a model of discrete perceptual cycles. PMID:28276493

Cross-class resistance to non-beta-lactam antimicrobials in extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.

PubMed

Procop, Gary W; Tuohy, Marion J; Wilson, Deborah A; Williams, Delisa; Hadziyannis, Emilia; Hall, Gerri S

2003-08-01

Extended spectrum beta-lactamases are modified beta-lactamase enzymes that impart resistance to third-generation cephalosporins and make all beta-lactam antibiotics and cephalosporins useless for therapy. We compared the antimicrobial susceptibility profiles of extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing isolates of Klebsiella pneumoniae. The ESBL producers had significantly diminished susceptibility compared with the non-ESBL producers for gentamicin (P < .001), tobramycin (P < .001), amikacin (P < .005), trimethoprim-sulfamethoxazole (P < .01), ciprofloxacin (P < .001), and nitrofurantoin (P < .001). All isolates were susceptible to imipenem. ESBL-producing K pneumoniae may also be resistant to non-beta-lactam antibiotics. Therefore, susceptibility testing of these isolates is critical for guiding therapy.

Role of beta-alanine supplementation on muscle carnosine and exercise performance.

PubMed

Artioli, Guilherme Giannini; Gualano, Bruno; Smith, Abbie; Stout, Jeffrey; Lancha, Antonio Herbert

2010-06-01

In this narrative review, we present and discuss the current knowledge available on carnosine and beta-alanine metabolism as well as the effects of beta-alanine supplementation on exercise performance. Intramuscular acidosis has been attributed to be one of the main causes of fatigue during intense exercise. Carnosine has been shown to play a significant role in muscle pH regulation. Carnosine is synthesized in skeletal muscle from the amino acids l-histidine and beta-alanine. The rate-limiting factor of carnosine synthesis is beta-alanine availability. Supplementation with beta-alanine has been shown to increase muscle carnosine content and therefore total muscle buffer capacity, with the potential to elicit improvements in physical performance during high-intensity exercise. Studies on beta-alanine supplementation and exercise performance have demonstrated improvements in performance during multiple bouts of high-intensity exercise and in single bouts of exercise lasting more than 60 s. Similarly, beta-alanine supplementation has been shown to delay the onset of neuromuscular fatigue. Although beta-alanine does not improve maximal strength or VO2max, some aspects of endurance performance, such as anaerobic threshold and time to exhaustion, can be enhanced. Symptoms of paresthesia may be observed if a single dose higher than 800 mg is ingested. The symptoms, however, are transient and related to the increase in plasma concentration. They can be prevented by using controlled release capsules and smaller dosing strategies. No important side effect was related to the use of this amino acid so far. In conclusion, beta-alanine supplementation seems to be a safe nutritional strategy capable of improving high-intensity anaerobic performance.

Temporal integration property of stereopsis after higher-order aberration correction

PubMed Central

Kang, Jian; Dai, Yun; Zhang, Yudong

2015-01-01

Based on a binocular adaptive optics visual simulator, we investigated the effect of higher-order aberration correction on the temporal integration property of stereopsis. Stereo threshold for line stimuli, viewed in 550nm monochromatic light, was measured as a function of exposure duration, with higher-order aberrations uncorrected, binocularly corrected or monocularly corrected. Under all optical conditions, stereo threshold decreased with increasing exposure duration until a steady-state threshold was reached. The critical duration was determined by a quadratic summation model and the high goodness of fit suggested this model was reasonable. For normal subjects, the slope for stereo threshold versus exposure duration was about −0.5 on logarithmic coordinates, and the critical duration was about 200 ms. Both the slope and the critical duration were independent of the optical condition of the eye, showing no significant effect of higher-order aberration correction on the temporal integration property of stereopsis. PMID:26601010

First images of a digital autoradiography system based on a Medipix2 hybrid silicon pixel detector.

PubMed

Mettivier, Giovanni; Montesi, Maria Cristina; Russo, Paolo

2003-06-21

We present the first images of beta autoradiography obtained with the high-resolution hybrid pixel detector consisting of the Medipix2 single photon counting read-out chip bump-bonded to a 300 microm thick silicon pixel detector. This room temperature system has 256 x 256 square pixels of 55 microm pitch (total sensitive area of 14 x 14 mm2), with a double threshold discriminator and a 13-bit counter in each pixel. It is read out via a dedicated electronic interface and control software, also developed in the framework of the European Medipix2 Collaboration. Digital beta autoradiograms of 14C microscale standard strips (containing separate bands of increasing specific activity in the range 0.0038-32.9 kBq g(-1)) indicate system linearity down to a total background noise of 1.8 x 10(-3) counts mm(-2) s(-1). The minimum detectable activity is estimated to be 0.012 Bq for 36,000 s exposure and 0.023 Bq for 10,800 s exposure. The measured minimum detection threshold is less than 1600 electrons (equivalent to about 6 keV Si). This real-time system for beta autoradiography offers lower pixel pitch and higher sensitive area than the previous Medipix1-based system. It has a 14C sensitivity better than that of micro channel plate based systems, which, however, shows higher spatial resolution and sensitive area.

The effect of strenuous exercise and beta-adrenergic blockade on the visual performance of juvenile rainbow trout, Oncorhynchus mykiss.

PubMed

Herbert, N A; Wells, R M G

2002-12-01

It is hypothesised that the visual performance of rainbow trout, Oncorhynchus mykiss, will be impaired by strenuous exercise as a result of metabolic stress (blood lactacidosis) that activates the Root effect and limits the oxygen-carrying capacity of blood flowing to the eye. The ability to resolve high contrast objects on a moving background, as a measure of visual performance, was quantified pre- and post-exercise using the optomotor response. Strenuous exercise induced a metabolic acidosis (8.0 mmol l(-1) blood lactate) and a significant red cell swelling response but no change in the optomotor response threshold (120 min of arc) was observed. Beta-adrenergic blockade (propranolol) abolished post-exercise red cell swelling but optomotor response thresholds were still maintained at 120 min of arc despite a significant blood lactate load (7.8 mmol l(-1)). The choroid rete mirabile of the trout is extremely well developed (rete area:eye area = 0.39) and may maintain visual performance by ensuring a relatively direct supply of oxygen to the central regions of the avascular retina. Exercised fish under beta-adrenergic blockade exhibited an enhanced optomotor response at 240-300 min of arc. Assuming that these responses reflect "tunnel vision", adrenergic regulation of red cell function may preserve a high ocular PO(2) gradient that satisfies the oxygen demand of peripheral retinal cells.

Transforming growth factor-beta1 accelerates resorption of a calcium carbonate biomaterial in periodontal defects.

PubMed

Koo, Ki-Tae; Susin, Cristiano; Wikesjö, Ulf M E; Choi, Seong-Ho; Kim, Chong-Kwan

2007-04-01

In a previous study, recombinant human transforming growth factor-beta1 (rhTGF-beta(1)) in a calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for guided tissue regeneration (GTR) to study whether rhTGF-beta(1) would enhance or accelerate periodontal regeneration. The results showed minimal benefits of rhTGF-beta(1), and a clear account for this could not be offered. One potential cause may be that the rhTGF-beta(1) formulation was biologically inactive. Several growth or differentiation factors have been suggested to accelerate degradation of biomaterials used as carriers. The objective of this study was to evaluate possible activity of rhTGF-beta(1) on biodegradation of the calcium carbonate carrier. rhTGF-beta(1) in a putty-formulated particulate calcium carbonate carrier was implanted into critical-size, supraalveolar periodontal defects under conditions for GTR in five beagle dogs. Contralateral defects received the calcium carbonate carrier combined with GTR without rhTGF-beta(1) (control). The animals were euthanized at week 4 post-surgery and block biopsies of the defect sites were collected for histologic and histometric analysis. Radiographs were obtained at defect creation and weeks 2 and 4 after defect creation. No statistically significant differences were observed in new bone formation (bone height and area) among the treatments. However, total residual carrier was significantly reduced in sites receiving rhTGF-beta(1) compared to control (P = 0.04). Similarly, carrier density was considerably reduced in sites receiving rhTGF-beta(1) compared to control; the difference was borderline statistically significant (P = 0.06). Within the limitations of the study, it may be concluded that rhTGF-beta(1) accelerates biodegradation of a particulate calcium carbonate biomaterial, indicating a biologic activity of the rhTGF-beta(1) formulation apparently not encompassing enhanced or accelerated periodontal regeneration.

Chemical evolution via beta decay: a case study in strontium-90

NASA Astrophysics Data System (ADS)

Marks, N. A.; Carter, D. J.; Sassi, M.; Rohl, A. L.; Sickafus, K. E.; Uberuaga, B. P.; Stanek, C. R.

2013-02-01

Using 90Sr as a representative isotope, we present a framework for understanding beta decay within the solid state. We quantify three key physical and chemical principles, namely momentum-induced recoil during the decay event, defect creation due to physical displacement, and chemical evolution over time. A fourth effect, that of electronic excitation, is also discussed, but this is difficult to quantify and is strongly material dependent. The analysis is presented for the specific cases of SrTiO3 and SrH2. By comparing the recoil energy with available threshold displacement data we show that in many beta-decay situations defects such as Frenkel pairs will not be created during decay as the energy transfer is too low. This observation leads to the concept of chemical evolution over time, which we quantify using density functional theory. Using a combination of Bader analysis, phonon calculations and cohesive energy calculations, we show that beta decay leads to counter-intuitive behavior that has implications for nuclear waste storage and novel materials design.

Chemical evolution via beta decay: a case study in strontium-90.

PubMed

Marks, N A; Carter, D J; Sassi, M; Rohl, A L; Sickafus, K E; Uberuaga, B P; Stanek, C R

2013-02-13

Using (90)Sr as a representative isotope, we present a framework for understanding beta decay within the solid state. We quantify three key physical and chemical principles, namely momentum-induced recoil during the decay event, defect creation due to physical displacement, and chemical evolution over time. A fourth effect, that of electronic excitation, is also discussed, but this is difficult to quantify and is strongly material dependent. The analysis is presented for the specific cases of SrTiO(3) and SrH(2). By comparing the recoil energy with available threshold displacement data we show that in many beta-decay situations defects such as Frenkel pairs will not be created during decay as the energy transfer is too low. This observation leads to the concept of chemical evolution over time, which we quantify using density functional theory. Using a combination of Bader analysis, phonon calculations and cohesive energy calculations, we show that beta decay leads to counter-intuitive behavior that has implications for nuclear waste storage and novel materials design.

Fast fission neutron detection using the Cherenkov effect

NASA Astrophysics Data System (ADS)

Millard, Matthew James

The Cherenkov effect in optically clear media of varying indices of refraction and composition was investigated for quantification of fast neutrons. The ultimate application of the proposed detection system is criticality monitoring. The optically clear medium, composed of select target nuclei, was coupled to a photomultiplier tube. Neutron reaction products of the target nuclei contained within the optical medium emit beta particles and gamma rays that produce Cherenkov photons within the medium which can be detected. Assessed media include quartz (SiO2), sapphire (Al2O3), spinel (MgAl2O4), and zinc sulfide (ZnS), which were irradiated with un-moderated 252Cf. Monte Carlo N-Particle (MCNP) code simulations were conducted to quantify the neutron flux incident on the media. High resolution gamma-ray spectroscopic measurements of the samples were conducted to verify the MCNP estimate. The threshold reactions of interest were 28Si (n, p) 28Al, 27 Al (n, p) 27Mg, 24Mg(n, p)24 Na, and 64Zn(n, p)64Cu which have neutron reaction cross sections in the 1 to 10 MeV range on the order of 0.1 barn. The detection system offers a unique way to measure a criticality event; it can count in place, making retrieval by emergency personnel unnecessary.

Critical dynamics on a large human Open Connectome network

NASA Astrophysics Data System (ADS)

Ódor, Géza

2016-12-01

Extended numerical simulations of threshold models have been performed on a human brain network with N =836 733 connected nodes available from the Open Connectome Project. While in the case of simple threshold models a sharp discontinuous phase transition without any critical dynamics arises, variable threshold models exhibit extended power-law scaling regions. This is attributed to fact that Griffiths effects, stemming from the topological or interaction heterogeneity of the network, can become relevant if the input sensitivity of nodes is equalized. I have studied the effects of link directness, as well as the consequence of inhibitory connections. Nonuniversal power-law avalanche size and time distributions have been found with exponents agreeing with the values obtained in electrode experiments of the human brain. The dynamical critical region occurs in an extended control parameter space without the assumption of self-organized criticality.

A test of critical thresholds and their indicators in a desertification-prone ecosystem: more resilience than we thought

USDA-ARS?s Scientific Manuscript database

Theoretical models predict that dryland ecosystems can cross critical thresholds after which vegetation loss is independent of initial drivers, but experimental data are nonexistent. We used a long-term (13 year) pulse-perturbation experiment featuring heavy grazing and shrub removal to determine i...

Rainfall threshold definition using an entropy decision approach and radar data

NASA Astrophysics Data System (ADS)

Montesarchio, V.; Ridolfi, E.; Russo, F.; Napolitano, F.

2011-07-01

Flash flood events are floods characterised by a very rapid response of basins to storms, often resulting in loss of life and property damage. Due to the specific space-time scale of this type of flood, the lead time available for triggering civil protection measures is typically short. Rainfall threshold values specify the amount of precipitation for a given duration that generates a critical discharge in a given river cross section. If the threshold values are exceeded, it can produce a critical situation in river sites exposed to alluvial risk. It is therefore possible to directly compare the observed or forecasted precipitation with critical reference values, without running online real-time forecasting systems. The focus of this study is the Mignone River basin, located in Central Italy. The critical rainfall threshold values are evaluated by minimising a utility function based on the informative entropy concept and by using a simulation approach based on radar data. The study concludes with a system performance analysis, in terms of correctly issued warnings, false alarms and missed alarms.

Identification and comparative expression analysis of interleukin 2/15 receptor B chain in chickens infected with E. tenella

USDA-ARS?s Scientific Manuscript database

Background: Interleukin (IL) 2 and IL15 receptor beta chain (IL2/15Receptor beta, CD122) play critical roles in signal transduction for the biological activities of IL2 and IL15. Increased knowledge of non-mammalian IL2/15Receptor beta will enhance the understanding of IL2 and IL15 functions. Meth...

Clustered lot quality assurance sampling to assess immunisation coverage: increasing rapidity and maintaining precision.

PubMed

Pezzoli, Lorenzo; Andrews, Nick; Ronveaux, Olivier

2010-05-01

Vaccination programmes targeting disease elimination aim to achieve very high coverage levels (e.g. 95%). We calculated the precision of different clustered lot quality assurance sampling (LQAS) designs in computer-simulated surveys to provide local health officers in the field with preset LQAS plans to simply and rapidly assess programmes with high coverage targets. We calculated sample size (N), decision value (d) and misclassification errors (alpha and beta) of several LQAS plans by running 10 000 simulations. We kept the upper coverage threshold (UT) at 90% or 95% and decreased the lower threshold (LT) progressively by 5%. We measured the proportion of simulations with < or =d individuals unvaccinated or lower if the coverage was set at the UT (pUT) to calculate beta (1-pUT) and the proportion of simulations with >d unvaccinated individuals if the coverage was LT% (pLT) to calculate alpha (1-pLT). We divided N in clusters (between 5 and 10) and recalculated the errors hypothesising that the coverage would vary in the clusters according to a binomial distribution with preset standard deviations of 0.05 and 0.1 from the mean lot coverage. We selected the plans fulfilling these criteria: alpha < or = 5% beta < or = 20% in the unclustered design; alpha < or = 10% beta < or = 25% when the lots were divided in five clusters. When the interval between UT and LT was larger than 10% (e.g. 15%), we were able to select precise LQAS plans dividing the lot in five clusters with N = 50 (5 x 10) and d = 4 to evaluate programmes with 95% coverage target and d = 7 to evaluate programmes with 90% target. These plans will considerably increase the feasibility and the rapidity of conducting the LQAS in the field.

The rates and time-delay distribution of multiply imaged supernovae behind lensing clusters

NASA Astrophysics Data System (ADS)

Li, Xue; Hjorth, Jens; Richard, Johan

2012-11-01

Time delays of gravitationally lensed sources can be used to constrain the mass model of a deflector and determine cosmological parameters. We here present an analysis of the time-delay distribution of multiply imaged sources behind 17 strong lensing galaxy clusters with well-calibrated mass models. We find that for time delays less than 1000 days, at z = 3.0, their logarithmic probability distribution functions are well represented by P(log Δt) = 5.3 × 10-4Δttilde beta/M2502tilde beta, with tilde beta = 0.77, where M250 is the projected cluster mass inside 250 kpc (in 1014M⊙), and tilde beta is the power-law slope of the distribution. The resultant probability distribution function enables us to estimate the time-delay distribution in a lensing cluster of known mass. For a cluster with M250 = 2 × 1014M⊙, the fraction of time delays less than 1000 days is approximately 3%. Taking Abell 1689 as an example, its dark halo and brightest galaxies, with central velocity dispersions σ>=500kms-1, mainly produce large time delays, while galaxy-scale mass clumps are responsible for generating smaller time delays. We estimate the probability of observing multiple images of a supernova in the known images of Abell 1689. A two-component model of estimating the supernova rate is applied in this work. For a magnitude threshold of mAB = 26.5, the yearly rate of Type Ia (core-collapse) supernovae with time delays less than 1000 days is 0.004±0.002 (0.029±0.001). If the magnitude threshold is lowered to mAB ~ 27.0, the rate of core-collapse supernovae suitable for time delay observation is 0.044±0.015 per year.

Modulating drug loading and release profile of beta-cyclodextrin polymers by means of cross-linked degree.

PubMed

Wang, Qi-fang; Li, San-ming; Zhang, Yu-yang; Zhang, Hong

2011-02-01

The purpose of the present study is to use beta-cyclodextrin polymers (beta-CDP) with different cross-linked degree (CLD) to form inclusion complexes with ibuprofen and examine the effects of structural and compositional factors of beta-CDP on its drug loading and release behaviors. A series of beta-CDP with different CLD were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and 13C NMR spectrum. The beta-CDP was systemically characterized for the relation between the CLD of beta-CDP and the drug loading and release as well. The results of FT-IR and 13C NMR showed that similar peak-shaped vibration of beta-CDP and beta-CD implies that the polymer keeps the original characteristic structure of beta-CD. The CLD of the beta-CDP played a critical role in the drug loading and release, increasing the CLD resulted in reduction of drug loading, but increase in drug release.

Hinge residue I174 is critical for proper dNTP selection by DNA polymerase beta.

PubMed

Yamtich, Jen; Starcevic, Daniela; Lauper, Julia; Smith, Elenoe; Shi, Idina; Rangarajan, Sneha; Jaeger, Joachim; Sweasy, Joann B

2010-03-23

DNA polymerase beta (pol beta) is the key gap-filling polymerase in base excision repair, the DNA repair pathway responsible for repairing up to 20000 endogenous lesions per cell per day. Pol beta is also widely used as a model polymerase for structure and function studies, and several structural regions have been identified as being critical for the fidelity of the enzyme. One of these regions is the hydrophobic hinge, a network of hydrophobic residues located between the palm and fingers subdomains. Previous work by our lab has shown that hinge residues Y265, I260, and F272 are critical for polymerase fidelity by functioning in discrimination of the correct from incorrect dNTP during ground state binding. Our work aimed to elucidate the role of hinge residue I174 in polymerase fidelity. To study this residue, we conducted a genetic screen to identify mutants with a substitution at residue I174 that resulted in a mutator polymerase. We then chose the mutator mutant I174S for further study and found that it follows the same general kinetic pathway as and has an overall protein folding similar to that of wild-type (WT) pol beta. Using single-turnover kinetic analysis, we found that I174S exhibits decreased fidelity when inserting a nucleotide opposite a template base G, and this loss of fidelity is due primarily to a loss of discrimination during ground state dNTP binding. Molecular dynamics simulations show that mutation of residue I174 to serine results in an overall tightening of the hinge region, resulting in aberrant protein dynamics and fidelity. These results point to the hinge region as being critical in the maintenance of the proper geometry of the dNTP binding pocket.

Elliptic Euler-Poisson-Darboux equation, critical points and integrable systems

NASA Astrophysics Data System (ADS)

Konopelchenko, B. G.; Ortenzi, G.

2013-12-01

The structure and properties of families of critical points for classes of functions W(z,{\\overline{z}}) obeying the elliptic Euler-Poisson-Darboux equation E(1/2, 1/2) are studied. General variational and differential equations governing the dependence of critical points in variational (deformation) parameters are found. Explicit examples of the corresponding integrable quasi-linear differential systems and hierarchies are presented. There are the extended dispersionless Toda/nonlinear Schrödinger hierarchies, the ‘inverse’ hierarchy and equations associated with the real-analytic Eisenstein series E(\\beta ,{\\overline{\\beta }};1/2) among them. The specific bi-Hamiltonian structure of these equations is also discussed.

Transport modeling of the DIII-D high $${{\\beta}_{p}}$$ scenario and extrapolations to ITER steady-state operation

DOE PAGES

McClenaghan, Joseph; Garofalo, Andrea M.; Meneghini, Orso; ...

2017-08-03

In this study, transport modeling of a proposed ITER steady-state scenario based on DIII-D high poloidal-beta (more » $${{\\beta}_{p}}$$ ) discharges finds that ITB formation can occur with either sufficient rotation or a negative central shear q-profile. The high $${{\\beta}_{p}}$$ scenario is characterized by a large bootstrap current fraction (80%) which reduces the demands on the external current drive, and a large radius internal transport barrier which is associated with excellent normalized confinement. Modeling predictions of the electron transport in the high $${{\\beta}_{p}}$$ scenario improve as $${{q}_{95}}$$ approaches levels similar to typical existing models of ITER steady-state and the ion transport is turbulence dominated. Typical temperature and density profiles from the non-inductive high $${{\\beta}_{p}}$$ scenario on DIII-D are scaled according to 0D modeling predictions of the requirements for achieving a $Q=5$ steady-state fusion gain in ITER with 'day one' heating and current drive capabilities. Then, TGLF turbulence modeling is carried out under systematic variations of the toroidal rotation and the core q-profile. A high bootstrap fraction, high $${{\\beta}_{p}}$$ scenario is found to be near an ITB formation threshold, and either strong negative central magnetic shear or rotation in a high bootstrap fraction are found to successfully provide the turbulence suppression required to achieve $Q=5$.« less

Critical phenomena at the threshold of immediate merger in binary black hole systems: The extreme mass ratio case

NASA Astrophysics Data System (ADS)

Gundlach, Carsten; Akcay, Sarp; Barack, Leor; Nagar, Alessandro

2012-10-01

In numerical simulations of black hole binaries, Pretorius and Khurana [Classical Quantum Gravity 24, S83 (2007)CQGRDG0264-938110.1088/0264-9381/24/12/S07] have observed critical behavior at the threshold between scattering and immediate merger. The number of orbits scales as n≃-γln⁡|p-p*| along any one-parameter family of initial data such that the threshold is at p=p*. Hence, they conjecture that in ultrarelativistic collisions almost all the kinetic energy can be converted into gravitational waves if the impact parameter is fine-tuned to the threshold. As a toy model for the binary, they consider the geodesic motion of a test particle in a Kerr black hole spacetime, where the unstable circular geodesics play the role of critical solutions, and calculate the critical exponent γ. Here, we incorporate radiation reaction into this model using the self-force approximation. The critical solution now evolves adiabatically along a sequence of unstable circular geodesic orbits under the effect of the self-force. We confirm that almost all the initial energy and angular momentum are radiated on the critical solution. Our calculation suggests that, even for infinite initial energy, this happens over a finite number of orbits given by n∞≃0.41/η, where η is the (small) mass ratio. We derive expressions for the time spent on the critical solution, number of orbits and radiated energy as functions of the initial energy and impact parameter.

Validation of the BetaStar® Advanced for Beta-lactams Test Kit for the Screening of Bulk Tank and Tanker Truck Milks for the Presence of Beta-lactam Drug Residues.

PubMed

Denhartigh, Andrew; Reynolds, Lindsay; Palmer, Katherine; Klein, Frank; Rice, Jennifer; Rejman, John J

2018-05-18

A validation study was conducted for an immunochromatographic method (BetaStar ® Advanced for Beta-lactams) for the detection of beta-lactam residues in raw, commingled bovine milk. The assay detected amoxicillin, ampicillin, cloxacillin, penicillin, cephapirin, and ceftiofur below the U.S. Food and Drug Administration tolerance levels but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments. The results of internal and independent laboratory dose-response studies employing spiked samples were in agreement. The test detected all six drugs at the approximate 90/95% sensitivity levels in milk from cows treated with each drug. Selectivity of the assay was 100%, as no false-positive results were obtained in testing 1148 control milk samples. Testing the estimated 90/95% sensitivity level for amoxicillin (8.5 ppb), ampicillin (6.9 ppb), cloxacillin (8.9 ppb), penicillin (4.2 ppb), and cephapirin (17.6 ppb), and at 100 ppb for each antibiotic, resulted in 94-100% positive tests for each of the beta-lactam drugs. The results of ruggedness experiments established the operating parameter tolerances for the assay. Cross-reactivity testing established that the assay detects other certain beta-lactam drugs, but it does not cross-react with any of 30 drugs belonging to seven different drug classes. Abnormally high bacterial or somatic cell counts in raw milk produced no assay interference.

Beta ray spectroscopy based on a plastic scintillation detector/silicon surface barrier detector coincidence telescope

NASA Astrophysics Data System (ADS)

Horowitz, Y. S.; Hirning, C. R.; Yuen, P.; Aikens, M.

1994-01-01

Beta radiation is now recognized as a significant radiation safety problem and several international conferences have recently been devoted to the problems of mixed field beta/photon dosimetry. Conventional dosimetry applies algorithms to thermoluminescence dosimetry (TLD) multi-element badges which attempt to extract dose information based on the comparison of TL signals from ``thick/thin'' and/or ``bare/filtered'' elements. These may be grossly innacurate due to inadequate or non-existant knowledge of the energy spectrum of both the beta radiation and the accompanying photon field, as well as other factors. In this paper, we discuss the operation of a beta-ray energy spectrometer based on a two element, E × dE detector telescope intended to support dose algorithms with beta spectral information. Beta energies are measured via a 5 cm diameter × 2 cm thick BC-404 plastic scintillator preceded by a single, 100 μm thick, totally depleted, silicon dE detector. Photon events in the E detector are rejected by requiring a coincidence between the E and dE detectors. Photon rejection ratios vary from 225:1 at 1.25 MeV (60Co) to 360:1 at 0.36 MeV (133Ba). The spectrometer is capable of measuring electron energies from a lower energy coincidence threshold of approximately 125 keV to an upper limit of 3.5 MeV. This energy range spans the great majority of beta-emitting radionuclides in nuclear facilities.

Phospholipase C-mediated hydrolysis of phosphatidylcholine is a target of transforming growth factor beta 1 inhibitory signals.

PubMed Central

Diaz-Meco, M T; Dominguez, I; Sanz, L; Municio, M M; Berra, E; Cornet, M E; Garcia de Herreros, A; Johansen, T; Moscat, J

1992-01-01

Cell growth and tumor transformation can be restrained in certain cell systems by the action of transforming growth factor beta (TGF-beta). It has been established that the mechanism whereby TGF-beta 1 inhibits cell growth does not interfere with the triggering of early mitogenic signal transduction mechanisms. Phospholipase C-catalyzed hydrolysis of phosphatidylcholine (PC) is a relatively late step in the cascade activated by growth factors. Therefore, conceivably activation of phospholipase C-catalyzed hydrolysis of PC could be the target of TGF-beta 1 action. In the study reported here, we demonstrate that TGF-beta 1 inhibits the coupling of ras p21 to the activation of PC hydrolysis, which appears to be critical for the antiproliferative effects of TGF-beta 1. Images PMID:1309592

Self-Organization on Social Media: Endo-Exo Bursts and Baseline Fluctuations

PubMed Central

Oka, Mizuki; Hashimoto, Yasuhiro; Ikegami, Takashi

2014-01-01

A salient dynamic property of social media is bursting behavior. In this paper, we study bursting behavior in terms of the temporal relation between a preceding baseline fluctuation and the successive burst response using a frequency time series of 3,000 keywords on Twitter. We found that there is a fluctuation threshold up to which the burst size increases as the fluctuation increases and that above the threshold, there appears a variety of burst sizes. We call this threshold the critical threshold. Investigating this threshold in relation to endogenous bursts and exogenous bursts based on peak ratio and burst size reveals that the bursts below this threshold are endogenously caused and above this threshold, exogenous bursts emerge. Analysis of the 3,000 keywords shows that all the nouns have both endogenous and exogenous origins of bursts and that each keyword has a critical threshold in the baseline fluctuation value to distinguish between the two. Having a threshold for an input value for activating the system implies that Twitter is an excitable medium. These findings are useful for characterizing how excitable a keyword is on Twitter and could be used, for example, to predict the response to particular information on social media. PMID:25329610

Sadness enhances the experience of pain and affects pain-evoked cortical activities: an MEG study.

PubMed

Yoshino, Atsuo; Okamoto, Yasumasa; Onoda, Keiichi; Shishida, Kazuhiro; Yoshimura, Shinpei; Kunisato, Yoshihiko; Demoto, Yoshihiko; Okada, Go; Toki, Shigeru; Yamashita, Hidehisa; Yamawaki, Shigeto

2012-07-01

Pain is a multidimensional phenomenon. Previous psychological studies have shown that a person's subjective pain threshold can change when certain emotions are recognized. We examined this association with magnetoencephalography. Magnetic field strength was recorded with a 306-channel neuromagnetometer while 19 healthy subjects (7 female, 12 male; age range = 20-30 years) experienced pain stimuli in different emotional contexts induced by the presentation of sad, happy, or neutral facial stimuli. Subjects also rated their subjective pain intensity. We hypothesized that pain stimuli were affected by sadness induced by facial recognition. We found: 1) the intensity of subjective pain ratings increased in the sad emotional context compared to the happy and the neutral contexts, and 2) event-related desynchronization of lower beta bands in the right hemisphere after pain stimuli was larger in the sad emotional condition than in the happy emotional condition. Previous studies have shown that event-related desynchronization in these bands could be consistently observed over the primary somatosensory cortex. These findings suggest that sadness can modulate neural responses to pain stimuli, and that brain processing of pain stimuli had already been affected, at the level of the primary somatosensory cortex, which is critical for sensory processing of pain. We found that subjective pain ratings and cortical beta rhythms after pain stimuli are influenced by the sad emotional context. These results may contribute to understanding the broader relationship between pain and negative emotion. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

Moessbauer effect: Study of disordered magnetic systems

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

Chang, Xiao Sha.

1989-01-01

This dissertation describes Moessbauer spectroscopy studies of two chemically disordered binary, crystalline alloys having the composition A{sub 1-x}B{sub x}. Both systems are random 3d Heisenberg ferromagnets. In each case both A and B atoms carry a magnetic moment. The first study concerns a Moessbauer absorber experiment on Fe{sub 1-x} V{sub x}, in which the disorder in the critical region is of the annealed random exchange type. To eliminate the effect of concentration inhomogeneity, the measurement of the critical exponent {beta} was done on the alloy with x = 0.125, where dT{sub C}/dx = 0, yielding {beta} = 0.362(8) over themore » reduced temperature range 1.4 {times} 10{sup {minus}3} < t < 4.88 {times} 10{sup {minus}1}. This result confirms the theoretical prediction that the annealed disorder is irrelevant to critical behavior in this case. As expected the critical exponent {beta} is consistent with the expectation for the 3d Heisenberg model as well as the measured exponent of pure Fe. The second study involves a Moessbauer source experiment on {sup 57} CoPd{sub 0.80}Co{sub 0.20}, in which disorder is of the quenched random exchange type perturbed by a very weak random anisotropy interaction. The critical exponent {beta} deduced over the range 1 {times} 10{sup {minus}2} < t < 2 {times} 10{sup {minus}1} is 0.385(20), and is consistent with the theoretical prediction for quenched disordered 3d Heisenberg systems: the disorder is irrelevant to the critical behavior. However, because of the restricted range of reduced temperature, the result is insufficiently asymptotic to serve as a conclusive test of the theory. Outside the critical region the distribution of Fe{sup 57} hyperfine field in Pd{sub 0.80}Co{sub 0.20} is observed to have an anomalous temperature dependence characterized by a linear increase in the width of the field distribution for T/T{sub C} {ge} 0.6.« less

Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

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

Feng, Ying; Tsinghua University School of Medicine, Haidian District, Beijing 100084; Yang, Shi-gao

Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phasesmore » of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.« less

Climate and soil attributes determine plant species turnover in global drylands.

PubMed

Ulrich, Werner; Soliveres, Santiago; Maestre, Fernando T; Gotelli, Nicholas J; Quero, José L; Delgado-Baquerizo, Manuel; Bowker, Matthew A; Eldridge, David J; Ochoa, Victoria; Gozalo, Beatriz; Valencia, Enrique; Berdugo, Miguel; Escolar, Cristina; García-Gómez, Miguel; Escudero, Adrián; Prina, Aníbal; Alfonso, Graciela; Arredondo, Tulio; Bran, Donaldo; Cabrera, Omar; Cea, Alex; Chaieb, Mohamed; Contreras, Jorge; Derak, Mchich; Espinosa, Carlos I; Florentino, Adriana; Gaitán, Juan; Muro, Victoria García; Ghiloufi, Wahida; Gómez-González, Susana; Gutiérrez, Julio R; Hernández, Rosa M; Huber-Sannwald, Elisabeth; Jankju, Mohammad; Mau, Rebecca L; Hughes, Frederic Mendes; Miriti, Maria; Monerris, Jorge; Muchane, Muchai; Naseri, Kamal; Pucheta, Eduardo; Ramírez-Collantes, David A; Raveh, Eran; Romão, Roberto L; Torres-Díaz, Cristian; Val, James; Veiga, José Pablo; Wang, Deli; Yuan, Xia; Zaady, Eli

2014-12-01

Geographic, climatic, and soil factors are major drivers of plant beta diversity, but their importance for dryland plant communities is poorly known. This study aims to: i) characterize patterns of beta diversity in global drylands, ii) detect common environmental drivers of beta diversity, and iii) test for thresholds in environmental conditions driving potential shifts in plant species composition. 224 sites in diverse dryland plant communities from 22 geographical regions in six continents. Beta diversity was quantified with four complementary measures: the percentage of singletons (species occurring at only one site), Whittake's beta diversity (β(W)), a directional beta diversity metric based on the correlation in species occurrences among spatially contiguous sites (β(R 2 )), and a multivariate abundance-based metric (β(MV)). We used linear modelling to quantify the relationships between these metrics of beta diversity and geographic, climatic, and soil variables. Soil fertility and variability in temperature and rainfall, and to a lesser extent latitude, were the most important environmental predictors of beta diversity. Metrics related to species identity (percentage of singletons and β(W)) were most sensitive to soil fertility, whereas those metrics related to environmental gradients and abundance ((β(R 2 )) and β(MV)) were more associated with climate variability. Interactions among soil variables, climatic factors, and plant cover were not important determinants of beta diversity. Sites receiving less than 178 mm of annual rainfall differed sharply in species composition from more mesic sites (> 200 mm). Soil fertility and variability in temperature and rainfall are the most important environmental predictors of variation in plant beta diversity in global drylands. Our results suggest that those sites annually receiving ~ 178 mm of rainfall will be especially sensitive to future climate changes. These findings may help to define appropriate conservation strategies for mitigating effects of climate change on dryland vegetation.

Nuclear radiation-warning detector that measures impedance

DOEpatents

Savignac, Noel Felix; Gomez, Leo S; Yelton, William Graham; Robinson, Alex; Limmer, Steven

2013-06-04

This invention is a nuclear radiation-warning detector that measures impedance of silver-silver halide on an interdigitated electrode to detect light or radiation comprised of alpha particles, beta particles, gamma rays, X rays, and/or neutrons. The detector is comprised of an interdigitated electrode covered by a layer of silver halide. After exposure to alpha particles, beta particles, X rays, gamma rays, neutron radiation, or light, the silver halide is reduced to silver in the presence of a reducing solution. The change from the high electrical resistance (impedance) of silver halide to the low resistance of silver provides the radiation warning that detected radiation levels exceed a predetermined radiation dose threshold.

Critical threshold behavior for steady-state internal transport barriers in burning plasmas.

PubMed

García, J; Giruzzi, G; Artaud, J F; Basiuk, V; Decker, J; Imbeaux, F; Peysson, Y; Schneider, M

2008-06-27

Burning tokamak plasmas with internal transport barriers are investigated by means of integrated modeling simulations. The barrier sustainment in steady state, differently from the barrier formation process, is found to be characterized by a critical behavior, and the critical number of the phase transition is determined. Beyond a power threshold, alignment of self-generated and noninductively driven currents occurs and steady state becomes possible. This concept is applied to simulate a steady-state scenario within the specifications of the International Thermonuclear Experimental Reactor.

VISA is an adapter protein required for virus-triggered IFN-beta signaling.

PubMed

Xu, Liang-Guo; Wang, Yan-Yi; Han, Ke-Jun; Li, Lian-Yun; Zhai, Zhonghe; Shu, Hong-Bing

2005-09-16

Viral infection or stimulation of TLR3 triggers signaling cascades, leading to activation of the transcription factors IRF-3 and NF-kappaB, which collaborate to induce transcription of type I interferon (IFN) genes. In this study, we identified a protein termed VISA (for virus-induced signaling adaptor) as a critical component in the IFN-beta signaling pathways. VISA recruits IRF-3 to the cytoplasmic viral dsRNA sensor RIG-I. Depletion of VISA inhibits virus-triggered and RIG-I-mediated activation of IRF-3, NF-kappaB, and the IFN-beta promoter, suggesting that VISA plays a central role in virus-triggered TLR3-independent IFN-beta signaling. Our data also indicate that VISA interacts with TRIF and TRAF6 and mediates bifurcation of the TLR3-triggered NF-kappaB and IRF-3 activation pathways. These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling.

ESR study of aqueous dispersions of beta-lactoglobulin and spin-labelled glyceryl monostearate.

PubMed

Van Gorkom, M; Van der Molen, M H; Korver, O

1975-05-05

From the ESR spectra of aqueous dispersions of synthetic glyceryl monostearate (spin labelled at C-12) a critical micelle concentration of 30 mumol/l at room temperature was obtained, which agrees with that deduced from surface tension measurements. At monoglyceride concentrations smaller or larger than the critical micelle concentration, the monomers show increased motional restriction with increasing molar ratio of beta-lactoglobulin to monoglyceride up to a value of 10, as determined from calculated rotational correlation times; A similar progressive interaction was deduced from spectral changes observed on equimolar dispersions of beta-lactoglobulin and monoglyceride on raising the temperature to 55 degrees C at which the protein and monoglyceride coprecipitate. The relevance of these finding for non-labelled monoglyceride dispersions is indicated by the similarity of the pH-dependent flocculation behaviour of labelled and non-labelled monoglycerides, both in the absence and presence of beta-lactoglobulin; In addition, proton magnetic resonance and mechanical stability measurements suggest that spin-labelled glyceryl monosterate behaves analogously to non-labelled glyceryl monooleate.

Rayleigh-Benard Convection in a Fluid with Prandtl Number Near One

NASA Astrophysics Data System (ADS)

Hu, Yuchou

1995-01-01

Studies of Rayleigh-Benard convection rotated about a vertical axis in cylindrical geometries with the shadowgraph imaging method are reported. The convection cells had radius-to-height ratios Gamma of between 23 and 52. The working fluid was CO _2 at 16 to 32 bar with Prandtl numbers ranging from 0.85 to 0.98. The results at zero rotation are presented first. For one of the cells (Gamma = 43), axisymmetric convection rolls were stable above onset up to epsilonequivDelta T/Delta T_{c}-1=0.19, where Delta T_{c} is the critical temperature difference. The amplitude of the center of the concentric patterns, the umbilicus, much larger near onset than that of the outlying region, grew as epsilon^{beta_ 1}, with beta_1=0.27 +/-0.04. Outside the umbilicus, the amplitude grew as epsilon^{beta_2 }, with beta_2 = 0.48 +/- 0.04. Pattern dynamics, wavenumbers, spatially-averaged roll-curvature, and sidewall roll-orientation as a function of epsilon are presented for a Gamma = 40 cell. As epsilon was increased, the skewed-varicose instability was first observed at epsilon~ 0.09, and roll -nucleating sidewall-foci were seen for epsilon _sp{~}{>} 0.15. The average roll curvature remained relatively constant for 0.2 _sp{~} {<} epsilon _sp{ ~}{<} 0.5, contrary to general expectation of increasing curvature with epsilon . Spiral-defect chaos appeared at epsilon ~ 0.55. Coincident with the increase in spiral-defect activity was a decrease in the average wavenumber and a marked increase in the sidewall-foci roll -nucleation frequency and average roll curvature. The thresholds of the onset of spiral-defect chaos for Gamma = 28, 40, and 52 were all at epsilon ~ 0.55. For rotating convection, pattern evolution at Gamma = 40 are described for dimensionless rotation rate Omega up to 20 and compared with observations at zero rotation. The Kuppers -Lortz instability was observed at the onset of convection at Omega~9 and co-existed with the skewed-varicose instability. For Omega _sp{~}{<} 11, the Kuppers-Lortz instability occurred via propagation of fronts initiated near the sidewall whereas at higher Omega fronts appearing spontaneously away from the sidewall became dominant. For Omega _sp{~}{>} 13, the Kuppers-Lortz angle was 60^{ circ}+/-1^{circ} , and the time scaling of the pattern dynamics showed a power-law dependence on epsilon with an exponent of 0.6 +/- 0.1. The threshold for spiral-defect chaos was depressed by rotation with spirals appearing at epsilon~0.40 at Omega = 8.8. The preferential inward-winding direction of the spirals was the same as the direction of the system rotation. The average wavenumber at onset of convection agreed with theoretical calculations and decreased with increasing epsilon. Quantitative measurements of the sidewall obliqueness show a general trend of rolls ending less perpendicular to the sidewall with increasing Omega for Omega<=q 9.

Phase-space dependent critical gradient behavior of fast-ion transport due to Alfvén eigenmodes

DOE PAGES

Collins, C. S.; Heidbrink, W. W.; Podestà, M.; ...

2017-06-09

Experiments in the DIII-D tokamak show that many overlapping small-amplitude Alfv en eigenmodes (AEs) cause fast-ion transport to sharply increase above a critical threshold, leading to fast-ion density profile resilience and reduced fusion performance. The threshold is above the AE linear stability limit and varies between diagnostics that are sensitive to different parts of fast-ion phase-space. A comparison with theoretical analysis using the nova and orbit codes shows that, for the neutral particle diagnostic, the threshold corresponds to the onset of stochastic particle orbits due to wave-particle resonances with AEs in the measured region of phase space. We manipulated themore » bulk fast-ion distribution and instability behavior through variations in beam deposition geometry, and no significant differences in the onset threshold outside of measurement uncertainties were found, in agreement with the theoretical stochastic threshold analysis. Simulations using the `kick model' produce beam ion density gradients consistent with the empirically measured radial critical gradient and highlight the importance of including the energy and pitch dependence of the fast-ion distribution function in critical gradient models. The addition of electron cyclotron heating changes the types of AEs present in the experiment, comparatively increasing the measured fast-ion density and radial gradient. Our studies provide the basis for understanding how to avoid AE transport that can undesirably redistribute current and cause fast-ion losses, and the measurements are being used to validate AE-induced transport models that use the critical gradient paradigm, giving greater confidence when applied to ITER.« less

Phase-space dependent critical gradient behavior of fast-ion transport due to Alfvén eigenmodes

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

Collins, C. S.; Heidbrink, W. W.; Podestà, M.

Experiments in the DIII-D tokamak show that many overlapping small-amplitude Alfv en eigenmodes (AEs) cause fast-ion transport to sharply increase above a critical threshold, leading to fast-ion density profile resilience and reduced fusion performance. The threshold is above the AE linear stability limit and varies between diagnostics that are sensitive to different parts of fast-ion phase-space. A comparison with theoretical analysis using the nova and orbit codes shows that, for the neutral particle diagnostic, the threshold corresponds to the onset of stochastic particle orbits due to wave-particle resonances with AEs in the measured region of phase space. We manipulated themore » bulk fast-ion distribution and instability behavior through variations in beam deposition geometry, and no significant differences in the onset threshold outside of measurement uncertainties were found, in agreement with the theoretical stochastic threshold analysis. Simulations using the `kick model' produce beam ion density gradients consistent with the empirically measured radial critical gradient and highlight the importance of including the energy and pitch dependence of the fast-ion distribution function in critical gradient models. The addition of electron cyclotron heating changes the types of AEs present in the experiment, comparatively increasing the measured fast-ion density and radial gradient. Our studies provide the basis for understanding how to avoid AE transport that can undesirably redistribute current and cause fast-ion losses, and the measurements are being used to validate AE-induced transport models that use the critical gradient paradigm, giving greater confidence when applied to ITER.« less

Extending the excluded volume for percolation threshold estimates in polydisperse systems: The binary disk system

DOE PAGES

Meeks, Kelsey; Pantoya, Michelle L.; Green, Micah; ...

2017-06-01

For dispersions containing a single type of particle, it has been observed that the onset of percolation coincides with a critical value of volume fraction. When the volume fraction is calculated based on excluded volume, this critical percolation threshold is nearly invariant to particle shape. The critical threshold has been calculated to high precision for simple geometries using Monte Carlo simulations, but this method is slow at best, and infeasible for complex geometries. This article explores an analytical approach to the prediction of percolation threshold in polydisperse mixtures. Specifically, this paper suggests an extension of the concept of excluded volume,more » and applies that extension to the 2D binary disk system. The simple analytical expression obtained is compared to Monte Carlo results from the literature. In conclusion, the result may be computed extremely rapidly and matches key parameters closely enough to be useful for composite material design.« less

Interleukin-1 may link helplessness-hopelessness with cancer progression: a proposed model.

PubMed

Argaman, Miriam; Gidron, Yori; Ariad, Shmuel

2005-01-01

A model of the relations between psychological factors and cancer progression should include brain and systemic components and their link with critical cellular stages in cancer progression. We present a psychoneuroimmunological (PNI) model that links helplessness-hopelessness (HH) with cancer progression via interleukin-1beta (IL-1beta). IL-1beta was elevated in the brain following exposure to inescapable shock, and HH was minimized by antagonizing cerebral IL-1beta. Elevated cerebral IL-1beta increased cancer metastasis in animals. Inescapable shock was associated with systemic elevations of IL-1beta and peripheral IL-1beta was associated with escape from apoptosis, angiogenesis, and metastasis. Involvement of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis are discussed. Future studies need to identify the role of additional factors in this PNI pathway.

Epidermal growth factor increases cortisol production and type II 3 beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase expression in human adrenocortical carcinoma cells: evidence for a Stat5-dependent mechanism.

PubMed

Feltus, F Alex; Kovacs, William J; Nicholson, Wendell; Silva, Corrine M; Nagdas, Subir K; Ducharme, Nicole A; Melner, Michael H

2003-05-01

We tested the ability of epidermal growth factor (EGF) to regulate a key enzyme in the adrenal synthesis of glucocorticoids: human type II 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3 beta HSD). EGF treatment (25 ng/ml) of human adrenocortical carcinoma cells (H295R) resulted in a 5-fold increase in cortisol production and a corresponding 2-fold increase in 3 beta HSD mRNA. Experiments were performed to determine whether EGF is acting through a previously identified signal transducer and activator of transcription 5 (Stat5)-responsive element located from -110 to -118 in the human type II 3 beta HSD promoter. A Stat5 expression construct was cotransfected with a 3 beta HSD-chloramphenol acetyltransferase (CAT) reporter construct comprised of nucleotides -301-->+45 of the human type II 3 beta HSD promoter linked to the CAT reporter gene sequence. The addition of EGF at doses as low as 10 ng/ml resulted in an 11- to 15-fold increase in CAT activity. The introduction of 3-bp point mutations into critical nucleotides in the Stat5 response element obviated the EGF response. Either Stat5a or Stat5b isoforms induced CAT reporter expression upon treatment with EGF. These results demonstrate the ability of EGF to regulate the expression of a critical enzyme (3 beta HSD) in the production of cortisol and suggest a molecular mechanism by which this regulation occurs.

CASMO5 JENDL-4.0 and ENDF/B-VII.1beta4 libraries

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

Rhodes, J.; Gheorghiu, N.; Ferrer, R.

2012-07-01

This paper details the generation of neutron data libraries for the CASMO5 lattice physics code based on the recently released JENDL-4.0 and ENDF/B-VII.1beta4 nuclear data evaluations. This data represents state-of-the-art nuclear data for late-2011. The key features of the new evaluations are briefly described along with the procedure for processing of this data into CASMO5, 586-energy group neutron data libraries. Finally some CASMO5 results for standard UO{sub 2} and MOX critical experiments for the two new libraries and the current ENDF/B-VII.0 CASMO5 library are presented including the B and W 1810 series, DIMPLE S06A, S06B, TCA reflector criticals with ironmore » plates and the PNL-30-35 MOX criticals. The results show that CASMO5 with the new libraries is performing well for these criticals with a very slight edge in results to the JENDL-4.0 nuclear data evaluation over the ENDF/B-VII.1beta4 evaluation. Work is currently underway to generate a CASMO5 library based on the final ENDF/B-VII.R1 evaluation released Dec. 22, 2011. (authors)« less

Probability density function of non-reactive solute concentration in heterogeneous porous formations.

PubMed

Bellin, Alberto; Tonina, Daniele

2007-10-30

Available models of solute transport in heterogeneous formations lack in providing complete characterization of the predicted concentration. This is a serious drawback especially in risk analysis where confidence intervals and probability of exceeding threshold values are required. Our contribution to fill this gap of knowledge is a probability distribution model for the local concentration of conservative tracers migrating in heterogeneous aquifers. Our model accounts for dilution, mechanical mixing within the sampling volume and spreading due to formation heterogeneity. It is developed by modeling local concentration dynamics with an Ito Stochastic Differential Equation (SDE) that under the hypothesis of statistical stationarity leads to the Beta probability distribution function (pdf) for the solute concentration. This model shows large flexibility in capturing the smoothing effect of the sampling volume and the associated reduction of the probability of exceeding large concentrations. Furthermore, it is fully characterized by the first two moments of the solute concentration, and these are the same pieces of information required for standard geostatistical techniques employing Normal or Log-Normal distributions. Additionally, we show that in the absence of pore-scale dispersion and for point concentrations the pdf model converges to the binary distribution of [Dagan, G., 1982. Stochastic modeling of groundwater flow by unconditional and conditional probabilities, 2, The solute transport. Water Resour. Res. 18 (4), 835-848.], while it approaches the Normal distribution for sampling volumes much larger than the characteristic scale of the aquifer heterogeneity. Furthermore, we demonstrate that the same model with the spatial moments replacing the statistical moments can be applied to estimate the proportion of the plume volume where solute concentrations are above or below critical thresholds. Application of this model to point and vertically averaged bromide concentrations from the first Cape Cod tracer test and to a set of numerical simulations confirms the above findings and for the first time it shows the superiority of the Beta model to both Normal and Log-Normal models in interpreting field data. Furthermore, we show that assuming a-priori that local concentrations are normally or log-normally distributed may result in a severe underestimate of the probability of exceeding large concentrations.

How extreme was the October 2015 flood in the Carolinas? An assessment of flood frequency analysis and distribution tails

NASA Astrophysics Data System (ADS)

Phillips, R. C.; Samadi, S. Z.; Meadows, M. E.

2018-07-01

This paper examines the frequency, distribution tails, and peak-over-threshold (POT) of extreme floods through analysis that centers on the October 2015 flooding in North Carolina (NC) and South Carolina (SC), United States (US). The most striking features of the October 2015 flooding were a short time to peak (Tp) and a multi-hour continuous flood peak which caused intensive and widespread damages to human lives, properties, and infrastructure. The 2015 flooding was produced by a sequence of intense rainfall events which originated from category 4 hurricane Joaquin over a period of four days. Here, the probability distribution and distribution parameters (i.e., location, scale, and shape) of floods were investigated by comparing the upper part of empirical distributions of the annual maximum flood (AMF) and POT with light- to heavy- theoretical tails: Fréchet, Pareto, Gumbel, Weibull, Beta, and Exponential. Specifically, four sets of U.S. Geological Survey (USGS) gauging data from the central Carolinas with record lengths from approximately 65-125 years were used. Analysis suggests that heavier-tailed distributions are in better agreement with the POT and somewhat AMF data than more often used exponential (light) tailed probability distributions. Further, the threshold selection and record length affect the heaviness of the tail and fluctuations of the parent distributions. The shape parameter and its evolution in the period of record play a critical and poorly understood role in determining the scaling of flood response to intense rainfall.

The Threshold Level--For Schools?

ERIC Educational Resources Information Center

Lauerbach, Gerda

1979-01-01

Comments on the document "Threshold Level for Modern Language Learning Schools" (J. A. Van Ek, Strasbourg, 1976) and its appropriateness as a description of learning goals for the first years of foreign language teaching. Criticizes particularly the "reduced learning" concept, on which the threshold projects are based. (IFS/WGA)

Two-flash thresholds as a function of comparison stimulus duration.

DOT National Transportation Integrated Search

1970-09-01

The proposal that two-flash thresholds may be used as direct measures of the critical duration (tc) of Bloch's law was tested. Two-flash threshold was found to be an increasing function of comparison stimulus duration for durations of 3 to 22 msec. i...

Spreading dynamics of a SIQRS epidemic model on scale-free networks

NASA Astrophysics Data System (ADS)

Li, Tao; Wang, Yuanmei; Guan, Zhi-Hong

2014-03-01

In order to investigate the influence of heterogeneity of the underlying networks and quarantine strategy on epidemic spreading, a SIQRS epidemic model on the scale-free networks is presented. Using the mean field theory the spreading dynamics of the virus is analyzed. The spreading critical threshold and equilibria are derived. Theoretical results indicate that the critical threshold value is significantly dependent on the topology of the underlying networks and quarantine rate. The existence of equilibria is determined by threshold value. The stability of disease-free equilibrium and the permanence of the disease are proved. Numerical simulations confirmed the analytical results.

Meta-analysis for deriving age- and gender-specific dose-response relationships between urinary cadmium concentration and {beta} {sub 2}-microglobulinuria under environmental exposure

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

Gamo, Masashi; Ono, Kyoko; Nakanishi, Junko

2006-05-15

A meta-analysis was conducted to derive age- and gender-specific dose-response relationships between urinary cadmium (Cd) concentration and {beta} {sub 2}-microglobulinuria ({beta}2MG-uria) under environmental exposure. {beta}2MG-uria was defined by a cutoff point of 1000 {mu}g {beta} {sub 2}-microglobulin/g creatinine. We proposed a model for describing the relationships among the interindividual variabilities in urinary Cd concentration, the ratio of Cd concentrations in the target organ and in urine, and the threshold Cd concentration in the target organ. The parameters in the model were determined so that good agreement might be achieved between the prevalence rates of {beta}2MG-uria reported in the literature andmore » those estimated by the model. In this analysis, only the data from the literature on populations environmentally exposed to Cd were used. Using the model and estimated parameters, the prevalence rate of {beta}2MG-uria can be estimated for an age- and gender-specific subpopulation for which the distribution of urinary Cd concentrations is known. The maximum permissible level of urinary Cd concentration was defined as the maximum geometric mean of the urinary Cd concentration in an age- and gender-specific subpopulation that would not result in a statistically significant increase in the prevalence rate of {beta}2MG-uria. This was estimated to be approximately 3 {mu}g/g creatinine for a population in a small geographical area and approximately 2 {mu}g/g creatinine for a nationwide population.« less

BetaCavityWeb: a webserver for molecular voids and channels

PubMed Central

Kim, Jae-Kwan; Cho, Youngsong; Lee, Mokwon; Laskowski, Roman A.; Ryu, Seong Eon; Sugihara, Kokichi; Kim, Deok-Soo

2015-01-01

Molecular cavities, which include voids and channels, are critical for molecular function. We present a webserver, BetaCavityWeb, which computes these cavities for a given molecular structure and a given spherical probe, and reports their geometrical properties: volume, boundary area, buried area, etc. The server's algorithms are based on the Voronoi diagram of atoms and its derivative construct: the beta-complex. The correctness of the computed result and computational efficiency are both mathematically guaranteed. BetaCavityWeb is freely accessible at the Voronoi Diagram Research Center (VDRC) (http://voronoi.hanyang.ac.kr/betacavityweb). PMID:25904629

Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

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

Li, Jason Z.; Ke, Yuebin; Misra, Hara P.

Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone,more » a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with low NQO1 expression, mitochondria play a critical role in beta-Lp redox activation. • In cancer cells with high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1.« less

Critical thresholds in species` responses to landscape structure

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

With, K.A.; Crist, T.O.

1995-12-01

Critical thresholds are transition ranges across which small changes in spatial pattern produce abrupt shifts in ecological responses. Habitat fragmentation provides a familiar example of a critical threshold. As the landscape becomes dissected into smaller parcels of habitat. landscape connectivity-the functional linkage among habitat patches - may suddenly become disrupted, which may have important consequences for the distribution and persistence of populations. Landscape connectivity depends not only on the abundance and spatial patterning of habitat. but also on the habitat specificity and dispersal abilities of species. Habitat specialists with limited dispersal capabilities presumably have a much lower threshold to habitatmore » fragmentation than highly vagile species, which may perceive the landscape as functionally connected across a greater range of fragmentation severity. To determine where threshold effects in species, responses to landscape structure are likely to occur, a simulation model modified from percolation theory was developed. Our simulations predicted the distributional patterns of populations in different landscape mosaics, which we tested empirically using two grasshopper species (Orthoptera: Acrididae) that occur in the shortgrass prairie of north-central Colorado. The distribution of these two species in this grassland mosaic matched the predictions from our simulations. By providing quantitative predictions of threshold effects, this modelling approach may prove useful in the formulation of conservation strategies and assessment of land-use changes on species` distributional patterns and persistence.« less

HOMOLOGY MODELING OF THE ESTROGEN RECEPTOR SUBTYPE BETA (ER-BETA) AND CALCULATION OF LIGAND BINDING AFFINITIES. (R826133)

EPA Science Inventory

Abstract

Estrogen is a steroid hormone playing critical roles in physiological processes such as sexual differentiation and development, female and male reproductive processes, and bone health. Numerous natural and synthetic environmental compounds have been shown capa...

Learning Portals: Analyzing Threshold Concept Theory for LIS Education

ERIC Educational Resources Information Center

Tucker, Virginia M.; Weedman, Judith; Bruce, Christine S.; Edwards, Sylvia L.

2014-01-01

This paper explores the theoretical framework of threshold concepts and its potential for LIS education. Threshold concepts are key ideas, often troublesome and counterintuitive, that are critical to profound understanding of a domain. Once understood, they allow mastery of significant aspects of the domain, opening up new, previously inaccessible…

Meprin A and meprin {alpha} generate biologically functional IL-1{beta} from pro-IL-1{beta}

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

Herzog, Christian; University of Arkansas for Medical Sciences, Department of Medicine, Little Rock, AR 72205; Haun, Randy S.

The present study demonstrates that both oligomeric metalloendopeptidase meprin A purified from kidney cortex and recombinant meprin {alpha} are capable of generating biologically active IL-1{beta} from its precursor pro-IL-1{beta}. Amino-acid sequencing analysis reveals that meprin A and meprin {alpha} cleave pro-IL-1{beta} at the His{sup 115}-Asp{sup 116} bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin {beta} site. The biological activity of the pro-IL-1{beta} cleaved product produced by meprin A, determined by proliferative response of helper T-cells, was 3-fold higher to that of the IL-1{beta} product produced by meprin {beta}more » or caspase-1. In a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum IL-1{beta}, meprin inhibitor actinonin significantly reduces levels of serum IL-1{beta}. Meprin A and meprin {alpha} may therefore play a critical role in the production of active IL-1{beta} during inflammation and tissue injury.« less

Implementing reduced-risk integrated pest management in fresh-market cabbage: influence of sampling parameters, and validation of binomial sequential sampling plans for the cabbage looper (Lepidoptera Noctuidae).

PubMed

Burkness, Eric C; Hutchison, W D

2009-10-01

Populations of cabbage looper, Trichoplusiani (Lepidoptera: Noctuidae), were sampled in experimental plots and commercial fields of cabbage (Brasicca spp.) in Minnesota during 1998-1999 as part of a larger effort to implement an integrated pest management program. Using a resampling approach and the Wald's sequential probability ratio test, sampling plans with different sampling parameters were evaluated using independent presence/absence and enumerative data. Evaluations and comparisons of the different sampling plans were made based on the operating characteristic and average sample number functions generated for each plan and through the use of a decision probability matrix. Values for upper and lower decision boundaries, sequential error rates (alpha, beta), and tally threshold were modified to determine parameter influence on the operating characteristic and average sample number functions. The following parameters resulted in the most desirable operating characteristic and average sample number functions; action threshold of 0.1 proportion of plants infested, tally threshold of 1, alpha = beta = 0.1, upper boundary of 0.15, lower boundary of 0.05, and resampling with replacement. We found that sampling parameters can be modified and evaluated using resampling software to achieve desirable operating characteristic and average sample number functions. Moreover, management of T. ni by using binomial sequential sampling should provide a good balance between cost and reliability by minimizing sample size and maintaining a high level of correct decisions (>95%) to treat or not treat.

Magnetic structure of light nuclei from lattice QCD

DOE PAGES

Chang, Emmanuel; Detmold, William; Orginos, Kostas; ...

2015-12-09

Lattice QCD with background magnetic fields is used to calculate the magnetic moments and magnetic polarizabilities of the nucleons and of light nuclei withmore » $$A\\le4$$, along with the cross-section for the $M1$ transition $$np\\rightarrow d\\gamma$$, at the flavor SU(3)-symmetric point where the pion mass is $$m_\\pi\\sim 806$$ MeV. These magnetic properties are extracted from nucleon and nuclear energies in six uniform magnetic fields of varying strengths. The magnetic moments are presented in a recent Letter. For the charged states, the extraction of the polarizability requires careful treatment of Landau levels, which enter non-trivially in the method that is employed. The nucleon polarizabilities are found to be of similar magnitude to their physical values, with $$\\beta_p=5.22(+0.66/-0.45)(0.23) \\times 10^{-4}$$ fm$^3$ and $$\\beta_n=1.253(+0.056/-0.067)(0.055) \\times 10^{-4}$$ fm$^3$, exhibiting a significant isovector component. The dineutron is bound at these heavy quark masses and its magnetic polarizability, $$\\beta_{nn}=1.872(+0.121/-0.113)(0.082) \\times 10^{-4}$$ fm$^3$ differs significantly from twice that of the neutron. A linear combination of deuteron scalar and tensor polarizabilities is determined by the energies of the $$j_z=\\pm 1$$ deuteron states, and is found to be $$\\beta_{d,\\pm 1}=4.4(+1.6/-1.5)(0.2) \\times 10^{-4}$$ fm$^3$. The magnetic polarizabilities of the three-nucleon and four-nucleon systems are found to be positive and similar in size to those of the proton, $$\\beta_{^{3}\\rm He}=5.4(+2.2/-2.1)(0.2) \\times 10^{-4}$$ fm$^3$, $$\\beta_{^{3}\\rm H}=2.6(1.7)(0.1) \\times 10^{-4}$$ fm$^3$, $$\\beta_{^{4}\\rm He}=3.4(+2.0/-1.9)(0.2) \\times 10^{-4}$$ fm$^3$. Mixing between the $$j_z=0$$ deuteron state and the spin-singlet $np$ state induced by the background magnetic field is used to extract the short-distance two-nucleon counterterm, $${\\bar L}_1$$, of the pionless effective theory for $NN$ systems (equivalent to the meson-exchange current contribution in nuclear potential models), that dictates the cross-section for the $$np\\to d\\gamma$$ process near threshold. Thus, combined with previous determinations of NN scattering parameters, this enables an ab initio determination of the threshold cross-section at these unphysical masses.« less

SIRT6-mediated transcriptional suppression of Txnip is critical for pancreatic beta cell function and survival in mice.

PubMed

Qin, Kunhua; Zhang, Ning; Zhang, Zhao; Nipper, Michael; Zhu, Zhenxin; Leighton, Jake; Xu, Kexin; Musi, Nicolas; Wang, Pei

2018-04-01

Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system. Mice were assayed for islet morphology, glucose tolerance, glucose-stimulated insulin secretion and susceptibility to streptozotocin. Transcriptional regulatory functions of SIRT6 in primary islets were evaluated by RNA-Seq analysis. Reverse transcription-quantitative (RT-q)PCR and immunoblot were used to verify and investigate the gene expression changes. Chromatin occupancies of SIRT6, H3K9Ac, H3K56Ac and active RNA polymerase II were evaluated by chromatin immunoprecipitation. Deletion of Sirt6 in pancreatic endocrine progenitor cells did not affect endocrine morphology, beta cell mass or insulin production but did result in glucose intolerance and defective glucose-stimulated insulin secretion in mice. Conditional deletion of Sirt6 in adult beta cells reproduced the insulin secretion defect. Loss of Sirt6 resulted in aberrant upregulation of thioredoxin-interacting protein (TXNIP) in beta cells. SIRT6 deficiency led to increased acetylation of histone H3 lysine residue at 9 (H3K9Ac), acetylation of histone H3 lysine residue at 56 (H3K56Ac) and active RNA polymerase II at the promoter region of Txnip. SIRT6-deficient beta cells exhibited a time-dependent increase in H3K9Ac, H3K56Ac and TXNIP levels. Finally, beta cell-specific SIRT6-deficient mice showed increased sensitivity to streptozotocin. Our results reveal that SIRT6 suppresses Txnip expression in beta cells via deacetylation of histone H3 and plays a critical role in maintaining beta cell function and viability. Sequence data have been deposited in the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) with the accession code GSE104161.

Experimenting with ecosystem interaction networks in search of threshold potentials in real-world marine ecosystems.

PubMed

Thrush, Simon F; Hewitt, Judi E; Parkes, Samantha; Lohrer, Andrew M; Pilditch, Conrad; Woodin, Sarah A; Wethey, David S; Chiantore, Mariachiara; Asnaghi, Valentina; De Juan, Silvia; Kraan, Casper; Rodil, Ivan; Savage, Candida; Van Colen, Carl

2014-06-01

Thresholds profoundly affect our understanding and management of ecosystem dynamics, but we have yet to develop practical techniques to assess the risk that thresholds will be crossed. Combining ecological knowledge of critical system interdependencies with a large-scale experiment, we tested for breaks in the ecosystem interaction network to identify threshold potential in real-world ecosystem dynamics. Our experiment with the bivalves Macomona liliana and Austrovenus stutchburyi on marine sandflats in New Zealand demonstrated that reductions in incident sunlight changed the interaction network between sediment biogeochemical fluxes, productivity, and macrofauna. By demonstrating loss of positive feedbacks and changes in the architecture of the network, we provide mechanistic evidence that stressors lead to break points in dynamics, which theory predicts predispose a system to a critical transition.

Beta burst dynamics in Parkinson's disease OFF and ON dopaminergic medication.

PubMed

Tinkhauser, Gerd; Pogosyan, Alek; Tan, Huiling; Herz, Damian M; Kühn, Andrea A; Brown, Peter

2017-11-01

Exaggerated basal ganglia beta activity (13-35 Hz) is commonly found in patients with Parkinson's disease and can be suppressed by dopaminergic medication, with the degree of suppression being correlated with the improvement in motor symptoms. Importantly, beta activity is not continuously elevated, but fluctuates to give beta bursts. The percentage number of longer beta bursts in a given interval is positively correlated with clinical impairment in Parkinson's disease patients. Here we determine whether the characteristics of beta bursts are dependent on dopaminergic state. Local field potentials were recorded from the subthalamic nucleus of eight Parkinson's disease patients during temporary lead externalization during surgery for deep brain stimulation. The recordings took place with the patient quietly seated following overnight withdrawal of levodopa and after administration of levodopa. Beta bursts were defined by applying a common amplitude threshold and burst characteristics were compared between the two drug conditions. The amplitude of beta bursts, indicative of the degree of local neural synchronization, progressively increased with burst duration. Treatment with levodopa limited this evolution leading to a relative increase of shorter, lower amplitude bursts. Synchronization, however, was not limited to local neural populations during bursts, but also, when such bursts were cotemporaneous across the hemispheres, was evidenced by bilateral phase synchronization. The probability of beta bursts and the proportion of cotemporaneous bursts were reduced by levodopa. The percentage number of longer beta bursts in a given interval was positively related to motor impairment, while the opposite was true for the percentage number of short duration beta bursts. Importantly, the decrease in burst duration was also correlated with the motor improvement. In conclusion, we demonstrate that long duration beta bursts are associated with an increase in local and interhemispheric synchronization. This may compromise information coding capacity and thereby motor processing. Dopaminergic activity limits this uncontrolled beta synchronization by terminating long duration beta bursts, with positive consequences on network state and motor symptoms. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

An entropy decision approach in flash flood warning: rainfall thresholds definition

NASA Astrophysics Data System (ADS)

Montesarchio, V.; Napolitano, F.; Ridolfi, E.

2009-09-01

Flash floods events are floods characterised by very rapid response of the basins to the storms, and often they involve loss of life and damage to common and private properties. Due to the specific space-time scale of this kind of flood, generally only a short lead time is available for triggering civil protection measures. Thresholds values specify the precipitation amount for a given duration that generates a critical discharge in a given cross section. The overcoming of these values could produce a critical situation in river sites exposed to alluvial risk, so it is possible to compare directly the observed or forecasted precipitation with critical reference values, without running on line real time forecasting systems. This study is focused on the Mignone River basin, located in Central Italy. The critical rainfall threshold values are evaluated minimising an utility function based on the informative entropy concept. The study concludes with a system performance analysis, in terms of correctly issued warning, false alarms and missed alarms.

Small C-terminal domain phosphatases dephosphorylate the regulatory linker regions of Smad2 and Smad3 to enhance transforming growth factor-beta signaling.

PubMed

Wrighton, Katharine H; Willis, Danielle; Long, Jianyin; Liu, Fang; Lin, Xia; Feng, Xin-Hua

2006-12-15

Transforming growth factor-beta (TGF-beta) controls a diverse set of cellular processes, and its canonical signaling is mediated via TGF-beta-induced phosphorylation of receptor-activated Smads (2 and 3) at the C-terminal SXS motif. We recently discovered that PPM1A can dephosphorylate Smad2/3 at the C-terminal SXS motif, implicating a critical role for phosphatases in regulating TGF-beta signaling. Smad2/3 activity is also regulated by phosphorylation in the linker region (and N terminus) by a variety of intracellular kinases, making it a critical platform for cross-talk between TGF-beta and other signaling pathways. Using a functional genomic approach, we identified the small C-terminal domain phosphatase 1 (SCP1) as a specific phosphatase for Smad2/3 dephosphorylation in the linker and N terminus. A catalytically inactive SCP1 mutant (dnSCP1) had no effect on Smad2/3 phosphorylation in vitro or in vivo. Of the other FCP/SCP family members SCP2 and SCP3, but not FCP1, could also dephosphorylate Smad2/3 in the linker/N terminus. Depletion of SCP1/2/3 enhanced Smad2/3 linker phosphorylation. SCP1 increased TGF-beta-induced transcriptional activity in agreement with the idea that phosphorylation in the Smad2/3 linker must be removed for a full transcriptional response. SCP1 overexpression also counteracts the inhibitory effect of epidermal growth factor on TGF-beta-induced p15 expression. Taken together, this work identifies the first example of a Smad2/3 linker phosphatase(s) and reveals an important new substrate for SCPs.

Diversity of Rainfall Thresholds for early warning of hydro-geological disasters

NASA Astrophysics Data System (ADS)

De Luca, Davide L.; Versace, Pasquale

2017-06-01

For early warning of disasters induced by precipitation (such as floods and landslides), different kinds of rainfall thresholds are adopted, which vary from each other, on the basis on adopted hypotheses. In some cases, they represent the occurrence probability of an event (landslide or flood), in other cases the exceedance probability of a critical value for an assigned indicator I (a function of rainfall heights), and in further cases they only indicate the exceeding of a prefixed percentage a critical value for I, indicated as Icr. For each scheme, it is usual to define three different criticality levels (ordinary, moderate and severe), which are associated to warning levels, according to emergency plans. This work briefly discusses different schemes of rainfall thresholds, focusing attention on landslide prediction, with some applications to a real case study in Calabria region (southern Italy).

Akt interacts directly with Smad3 to regulate the sensitivity to TGF-beta induced apoptosis.

PubMed

Conery, Andrew R; Cao, Yanna; Thompson, E Aubrey; Townsend, Courtney M; Ko, Tien C; Luo, Kunxin

2004-04-01

Transforming growth factor beta (TGF-beta) induces both apoptosis and cell-cycle arrest in some cell lines, but only growth arrest in others. It is not clear how this differential response to TGF-beta is specified. Smad proteins are critical mediators of TGF-beta signalling. After stimulation by TGF-beta, Smad2 and Smad3 become phosphorylated by the activated TGF-beta receptor kinases, oligomerize with Smad4, translocate to the nucleus and regulate the expression of TGF-beta target genes. Here we report that the sensitivity to TGF-beta induced apoptosis is regulated by crosstalk between the Akt/PKB serine/threonine kinase and Smad3 through a mechanism that is independent of Akt kinase activity. Akt interacts directly with unphosphorylated Smad3 to sequester it outside the nucleus, preventing its phosphorylation and nuclear translocation. This results in inhibition of Smad3-mediated transcription and apoptosis. Furthermore, the ratio of Smad3 to Akt correlates with the sensitivity of cells to TGF-beta induced apoptosis. Alteration of this ratio changes the apoptotic, but not the growth-inhibitory, responses of cells to TGF-beta. These findings identify an important determinant of sensitivity to TGF-beta-induced apoptosis that involves crosstalk between the TGF-beta and phosphatidylinositol-3-OH kinase (PI(3)K) pathways.

Closed-loop adaptation of neurofeedback based on mental effort facilitates reinforcement learning of brain self-regulation.

PubMed

Bauer, Robert; Fels, Meike; Royter, Vladislav; Raco, Valerio; Gharabaghi, Alireza

2016-09-01

Considering self-rated mental effort during neurofeedback may improve training of brain self-regulation. Twenty-one healthy, right-handed subjects performed kinesthetic motor imagery of opening their left hand, while threshold-based classification of beta-band desynchronization resulted in proprioceptive robotic feedback. The experiment consisted of two blocks in a cross-over design. The participants rated their perceived mental effort nine times per block. In the adaptive block, the threshold was adjusted on the basis of these ratings whereas adjustments were carried out at random in the other block. Electroencephalography was used to examine the cortical activation patterns during the training sessions. The perceived mental effort was correlated with the difficulty threshold of neurofeedback training. Adaptive threshold-setting reduced mental effort and increased the classification accuracy and positive predictive value. This was paralleled by an inter-hemispheric cortical activation pattern in low frequency bands connecting the right frontal and left parietal areas. Optimal balance of mental effort was achieved at thresholds significantly higher than maximum classification accuracy. Rating of mental effort is a feasible approach for effective threshold-adaptation during neurofeedback training. Closed-loop adaptation of the neurofeedback difficulty level facilitates reinforcement learning of brain self-regulation. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A Threshold Model of Social Support, Adjustment, and Distress after Breast Cancer Treatment

ERIC Educational Resources Information Center

Mallinckrodt, Brent; Armer, Jane M.; Heppner, P. Paul

2012-01-01

This study examined a threshold model that proposes that social support exhibits a curvilinear association with adjustment and distress, such that support in excess of a critical threshold level has decreasing incremental benefits. Women diagnosed with a first occurrence of breast cancer (N = 154) completed survey measures of perceived support…

Sepsis and Inflammatory Response Mechanisms: An Activity Stress Model in Humans

DTIC Science & Technology

2001-01-31

anaerobic threshold yielded the reactions most typical of trauma. However, no mode of laboratory exercise induced a sustained and prolonged inflammatory...mobilization ....................................................................................... 9 8. Anaerobic threshold as a marker of the critical...after epmnephriei injection. Lymphocyte retention by lymph nodes, however, may contribute to post-injection lymphopenia. 8. Anaerobic Threshold as a

Nonlinear threshold behavior during the loss of Arctic sea ice.

PubMed

Eisenman, I; Wettlaufer, J S

2009-01-06

In light of the rapid recent retreat of Arctic sea ice, a number of studies have discussed the possibility of a critical threshold (or "tipping point") beyond which the ice-albedo feedback causes the ice cover to melt away in an irreversible process. The focus has typically been centered on the annual minimum (September) ice cover, which is often seen as particularly susceptible to destabilization by the ice-albedo feedback. Here, we examine the central physical processes associated with the transition from ice-covered to ice-free Arctic Ocean conditions. We show that although the ice-albedo feedback promotes the existence of multiple ice-cover states, the stabilizing thermodynamic effects of sea ice mitigate this when the Arctic Ocean is ice covered during a sufficiently large fraction of the year. These results suggest that critical threshold behavior is unlikely during the approach from current perennial sea-ice conditions to seasonally ice-free conditions. In a further warmed climate, however, we find that a critical threshold associated with the sudden loss of the remaining wintertime-only sea ice cover may be likely.

Nonlinear threshold behavior during the loss of Arctic sea ice

PubMed Central

Eisenman, I.; Wettlaufer, J. S.

2009-01-01

In light of the rapid recent retreat of Arctic sea ice, a number of studies have discussed the possibility of a critical threshold (or “tipping point”) beyond which the ice–albedo feedback causes the ice cover to melt away in an irreversible process. The focus has typically been centered on the annual minimum (September) ice cover, which is often seen as particularly susceptible to destabilization by the ice–albedo feedback. Here, we examine the central physical processes associated with the transition from ice-covered to ice-free Arctic Ocean conditions. We show that although the ice–albedo feedback promotes the existence of multiple ice-cover states, the stabilizing thermodynamic effects of sea ice mitigate this when the Arctic Ocean is ice covered during a sufficiently large fraction of the year. These results suggest that critical threshold behavior is unlikely during the approach from current perennial sea-ice conditions to seasonally ice-free conditions. In a further warmed climate, however, we find that a critical threshold associated with the sudden loss of the remaining wintertime-only sea ice cover may be likely. PMID:19109440

A threshold theory of the humor response.

PubMed

Epstein, Robert; Joker, Veronica R

2007-01-01

The humor response has long been considered mysterious, and it is given relatively little attention in modern experimental psychology, in spite of the fact that numerous studies suggest that it has substantial benefits for mood and health. Existing theories of humor fail to account for some of the most basic humor phenomena. On most occasions when a humor response occurs, certain verbal or visual stimuli (the "setup" stimuli, which function as an establishing operation) must precede a critical stimulus (such as a "punch line" or the final panel or critical feature of a cartoon), which then occasions a sudden "revelation" or "understanding"; this revelation is often accompanied by the humor response. We suggest that the setup stimuli increase the strength of the revelatory response to a point just below the threshold of awareness and that the critical stimulus, properly designed and timed, edges the revelatory response to a point just above threshold. We also suggest that it is this threshold phenomenon that produces most instances of the humor response. We discuss these issues in the context of some notable humor of Carl Rogers and B. F. Skinner.

Facilitation of Learning by Social-Emotional Feedback in Humans Is Beta-Noradrenergic-Dependent

ERIC Educational Resources Information Center

Mihov, Yoan; Mayer, Simon; Musshoff, Frank; Maier, Wolfgang; Kendrick, Keith M.; Hurlemann, Rene

2010-01-01

Adaptive behavior in dynamic environments critically depends on the ability to learn rapidly and flexibly from the outcomes of prior choices. In social environments, facial expressions of emotion often serve as performance feedback and thereby guide declarative learning. Abundant evidence implicates beta-noradrenergic signaling in the modulatory…

MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes.

PubMed

Ardestani, Amin; Paroni, Federico; Azizi, Zahra; Kaur, Supreet; Khobragade, Vrushali; Yuan, Ting; Frogne, Thomas; Tao, Wufan; Oberholzer, Jose; Pattou, Francois; Conte, Julie Kerr; Maedler, Kathrin

2014-04-01

Apoptotic cell death is a hallmark of the loss of insulin-producing beta cells in all forms of diabetes mellitus. Current treatments fail to halt the decline in functional beta cell mass, and strategies to prevent beta cell apoptosis and dysfunction are urgently needed. Here, we identified mammalian sterile 20-like kinase-1 (MST1) as a critical regulator of apoptotic beta cell death and function. Under diabetogenic conditions, MST1 was strongly activated in beta cells in human and mouse islets and specifically induced the mitochondrial-dependent pathway of apoptosis through upregulation of the BCL-2 homology-3 (BH3)-only protein BIM. MST1 directly phosphorylated the beta cell transcription factor PDX1 at T11, resulting in the latter's ubiquitination and degradation and thus in impaired insulin secretion. MST1 deficiency completely restored normoglycemia, beta cell function and survival in vitro and in vivo. We show MST1 as a proapoptotic kinase and key mediator of apoptotic signaling and beta cell dysfunction and suggest that it may serve as target for the development of new therapies for diabetes.

GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells.

PubMed

Tran, Dat Q; Andersson, John; Wang, Rui; Ramsey, Heather; Unutmaz, Derya; Shevach, Ethan M

2009-08-11

TGF-beta family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-beta is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFbeta-binding protein (LTBP) to produce a large latent form. Latent TGF-beta is also found on the surface of activated FOXP3(+) regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-beta to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-beta and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-beta expression on activated Tregs and recombinant latent TGF-beta1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-beta on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism.

Adverse CNS-effects of beta-adrenoceptor blockers.

PubMed

Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

Regional rainfall thresholds for landslide occurrence using a centenary database

NASA Astrophysics Data System (ADS)

Vaz, Teresa; Luís Zêzere, José; Pereira, Susana; Cruz Oliveira, Sérgio; Quaresma, Ivânia

2017-04-01

Rainfall is one of the most important triggering factors for landslides occurrence worldwide. The relation between rainfall and landslide occurrence is complex and some approaches have been focus on the rainfall thresholds identification, i.e., rainfall critical values that when exceeded can initiate landslide activity. In line with these approaches, this work proposes and validates rainfall thresholds for the Lisbon region (Portugal), using a centenary landslide database associated with a centenary daily rainfall database. The main objectives of the work are the following: i) to compute antecedent rainfall thresholds using linear and potential regression; ii) to define lower limit and upper limit rainfall thresholds; iii) to estimate the probability of critical rainfall conditions associated with landslide events; and iv) to assess the thresholds performance using receiver operating characteristic (ROC) metrics. In this study we consider the DISASTER database, which lists landslides that caused fatalities, injuries, missing people, evacuated and homeless people occurred in Portugal from 1865 to 2010. The DISASTER database was carried out exploring several Portuguese daily and weekly newspapers. Using the same newspaper sources, the DISASTER database was recently updated to include also the landslides that did not caused any human damage, which were also considered for this study. The daily rainfall data were collected at the Lisboa-Geofísico meteorological station. This station was selected considering the quality and completeness of the rainfall data, with records that started in 1864. The methodology adopted included the computation, for each landslide event, of the cumulative antecedent rainfall for different durations (1 to 90 consecutive days). In a second step, for each combination of rainfall quantity-duration, the return period was estimated using the Gumbel probability distribution. The pair (quantity-duration) with the highest return period was considered as the critical rainfall combination responsible for triggering the landslide event. Only events whose critical rainfall combinations have a return period above 3 years were included. This criterion reduces the likelihood of been included events whose triggering factor was other than rainfall. The rainfall quantity-duration threshold for the Lisbon region was firstly defined using the linear and potential regression. Considering that this threshold allow the existence of false negatives (i.e. events below the threshold) it was also identified the lower limit and upper limit rainfall thresholds. These limits were defined empirically by establishing the quantity-durations combinations bellow which no landslides were recorded (lower limit) and the quantity-durations combinations above which only landslides were recorded without any false positive occurrence (upper limit). The zone between the lower limit and upper limit rainfall thresholds was analysed using a probabilistic approach, defining the uncertainties of each rainfall critical conditions in the triggering of landslides. Finally, the performances of the thresholds obtained in this study were assessed using ROC metrics. This work was supported by the project FORLAND - Hydrogeomorphologic risk in Portugal: driving forces and application for land use planning [grant number PTDC/ATPGEO/1660/2014] funded by the Portuguese Foundation for Science and Technology (FCT), Portugal. Sérgio Cruz Oliveira is a post-doc fellow of the FCT [grant number SFRH/BPD/85827/2012].

Glycogen synthase kinase 3 beta alters anxiety-, depression-, and addiction-related behaviors and neuronal activity in the nucleus accumbens shell

PubMed Central

Crofton, Elizabeth J.; Nenov, Miroslav N.; Zhang, Yafang; Scala, Federico; Page, Sean A.; McCue, David L.; Li, Dingge; Hommel, Jonathan D.; Laezza, Fernanda; Green, Thomas A.

2017-01-01

Psychiatric disorders such as anxiety, depression and addiction are often comorbid brain pathologies thought to share common mechanistic biology. As part of the cortico-limbic circuit, the nucleus accumbens shell (NAcSh) plays a fundamental role in integrating information in the circuit, such that modulation of NAcSh circuitry alters anxiety, depression, and addiction-related behaviors. Intracellular kinase cascades in the NAcSh have proven important mediators of behavior. To investigate glycogen-synthase kinase 3 (GSK3) beta signaling in the NAcSh in vivo we knocked down GSK3beta expression with a novel adeno-associated viral vector (AAV2) and assessed changes in anxiety- and depression-like behavior and cocaine self-administration in GSK3beta knockdown rats. GSK3beta knockdown reduced anxiety-like behavior while increasing depression-like behavior and cocaine self-administration. Correlative electrophysiological recordings in acute brain slices were used to assess the effect of AAV-shGSK3beta on spontaneous firing and intrinsic excitability of tonically active interneurons (TANs), cells required for input and output signal integration in the NAcSh and for processing reward-related behaviors. Loose-patch recordings showed that TANs transduced by AAV-shGSK3beta exhibited reduction in tonic firing and increased spike half width. When assessed by whole-cell patch clamp recordings these changes were mirrored by reduction in action potential firing and accompanied by decreased hyperpolarization-induced depolarizing sag potentials, increased action potential current threshold, and decreased maximum rise time. These results suggest that silencing of GSK3beta in the NAcSh increases depression- and addiction-related behavior, possibly by decreasing intrinsic excitability of TANs. However, this study does not rule out contributions from other neuronal sub-types. PMID:28126496

Monitoring the eye lens: which dose quantity is adequate?

NASA Astrophysics Data System (ADS)

Behrens, R.; Dietze, G.

2010-07-01

Recent epidemiological studies suggest a rather low dose threshold (below 0.5 Gy) for the induction of a cataract of the eye lens. Some other studies even assume that there is no threshold at all. Therefore, protection measures have to be optimized and current dose limits for the eye lens may be reduced in the future. The question of which personal dose equivalent quantity is appropriate for monitoring the dose to the eye lens arises from this situation. While in many countries dosemeters calibrated in terms of the dose equivalent quantity Hp(0.07) have been seen as being adequate for monitoring the dose to the eye lens, this might be questionable in the case of reduced dose limits and, thus, it may become necessary to use the dose equivalent quantity Hp(3) for this purpose. To discuss this question, the dose conversion coefficients for the equivalent dose of the eye lens (in the following eye lens dose) were determined for realistic photon and beta radiation fields and compared with the values of the corresponding conversion coefficients for the different operational quantities. The values obtained lead to the following conclusions: in radiation fields where most of the dose comes from photons, especially x-rays, it is appropriate to use dosemeters calibrated in terms of Hp(0.07) on a slab phantom, while in other radiation fields (dominated by beta radiation or unknown contributions of photon and beta radiation) dosemeters calibrated in terms of Hp(3) on a slab phantom should be used. As an alternative, dosemeters calibrated in terms of Hp(0.07) on a slab phantom could also be used; however, in radiation fields containing beta radiation with the end point energy near 1 MeV, an overestimation of the eye lens dose by up to a factor of 550 is possible.

Monitoring the eye lens: which dose quantity is adequate?

PubMed

Behrens, R; Dietze, G

2010-07-21

Recent epidemiological studies suggest a rather low dose threshold (below 0.5 Gy) for the induction of a cataract of the eye lens. Some other studies even assume that there is no threshold at all. Therefore, protection measures have to be optimized and current dose limits for the eye lens may be reduced in the future. The question of which personal dose equivalent quantity is appropriate for monitoring the dose to the eye lens arises from this situation. While in many countries dosemeters calibrated in terms of the dose equivalent quantity H(p)(0.07) have been seen as being adequate for monitoring the dose to the eye lens, this might be questionable in the case of reduced dose limits and, thus, it may become necessary to use the dose equivalent quantity H(p)(3) for this purpose. To discuss this question, the dose conversion coefficients for the equivalent dose of the eye lens (in the following eye lens dose) were determined for realistic photon and beta radiation fields and compared with the values of the corresponding conversion coefficients for the different operational quantities. The values obtained lead to the following conclusions: in radiation fields where most of the dose comes from photons, especially x-rays, it is appropriate to use dosemeters calibrated in terms of H(p)(0.07) on a slab phantom, while in other radiation fields (dominated by beta radiation or unknown contributions of photon and beta radiation) dosemeters calibrated in terms of H(p)(3) on a slab phantom should be used. As an alternative, dosemeters calibrated in terms of H(p)(0.07) on a slab phantom could also be used; however, in radiation fields containing beta radiation with the end point energy near 1 MeV, an overestimation of the eye lens dose by up to a factor of 550 is possible.

Relationship Between Beta Cell Dysfunction and Severity of Disease Among Critically Ill Children: A STROBE-Compliant Prospective Observational Study.

PubMed

Liu, Ping-Ping; Lu, Xiu-Lan; Xiao, Zheng-Hui; Qiu, Jun; Zhu, Yi-Min

2016-05-01

Although beta cell dysfunction has been proved to predict prognosis among humans and animals, its prediction on severity of disease remains unclear among children. The present study was aimed to examine the relationship between beta cell dysfunction and severity of disease among critically ill children.This prospective study included 1146 critically ill children, who were admitted to Pediatric Intensive Care Unit (PICU) of Hunan Children's Hospital from November 2011 to August 2013. Information on characteristics, laboratory tests, and prognostic outcomes was collected. Homeostasis model assessment (HOMA)-β, evaluating beta cell function, was used to divide all participants into 4 groups: HOMA-β = 100% (group I, n = 339), 80% ≤ HOMA-β < 100% (group II, n = 71), 40% ≤ HOMA-β < 80% (group III, n = 293), and HOMA-β < 40% (group IV, n = 443). Severity of disease was assessed using the worst Sequential Organ Failure Assessment (SOFA) score, Pediatric Risk of Mortality (PRISM) III score, incidence of organ damage, septic shock, multiple organ dysfunction syndrome (MODS), mechanical ventilation (MV) and mortality. Logistic regression analysis was used to evaluate the risk of developing poor outcomes among patients in different HOMA-β groups, with group I as the reference group.Among 1146 children, incidence of HOMA-β < 100% was 70.41%. C-peptide and insulin declined with the decrement of HOMA-β (P < 0.01). C-reactive protein and procalcitonin levels, rather than white blood cell, were significantly different among 4 groups (P < 0.01). In addition, the worst SOFA score and the worst PRISMIII score increased with declined HOMA-β. For example, the worst SOFA score in group I, II, III, and IV was 1.55 ± 1.85, 1.71 ± 1.93, 1.92 ± 1.63, and 2.18 ± 1.77, respectively. Furthermore, patients with declined HOMA-β had higher risk of developing septic shock, MODS, MV, and mortality, even after adjusting age, gender, myocardial injury, and lung injury. For instance, compared with group I, the multivariate-adjusted odds ratio (95% confidence interval) for developing septic shock was 2.17 (0.59, 8.02), 2.94 (2.18, 6.46), and 2.76 (1.18, 6.46) among patients in group II, III, and IV, respectively.Beta cell dysfunction reflected the severity of disease among critically ill children. Therefore, assessment of beta cell function is critically important to reduce incidence of adverse events in PICU.

Climate and soil attributes determine plant species turnover in global drylands

PubMed Central

Maestre, Fernando T.; Gotelli, Nicholas J.; Quero, José L.; Delgado-Baquerizo, Manuel; Bowker, Matthew A.; Eldridge, David J.; Ochoa, Victoria; Gozalo, Beatriz; Valencia, Enrique; Berdugo, Miguel; Escolar, Cristina; García-Gómez, Miguel; Escudero, Adrián; Prina, Aníbal; Alfonso, Graciela; Arredondo, Tulio; Bran, Donaldo; Cabrera, Omar; Cea, Alex; Chaieb, Mohamed; Contreras, Jorge; Derak, Mchich; Espinosa, Carlos I.; Florentino, Adriana; Gaitán, Juan; Muro, Victoria García; Ghiloufi, Wahida; Gómez-González, Susana; Gutiérrez, Julio R.; Hernández, Rosa M.; Huber-Sannwald, Elisabeth; Jankju, Mohammad; Mau, Rebecca L.; Hughes, Frederic Mendes; Miriti, Maria; Monerris, Jorge; Muchane, Muchai; Naseri, Kamal; Pucheta, Eduardo; Ramírez-Collantes, David A.; Raveh, Eran; Romão, Roberto L.; Torres-Díaz, Cristian; Val, James; Veiga, José Pablo; Wang, Deli; Yuan, Xia; Zaady, Eli

2015-01-01

Aim Geographic, climatic, and soil factors are major drivers of plant beta diversity, but their importance for dryland plant communities is poorly known. This study aims to: i) characterize patterns of beta diversity in global drylands, ii) detect common environmental drivers of beta diversity, and iii) test for thresholds in environmental conditions driving potential shifts in plant species composition. Location 224 sites in diverse dryland plant communities from 22 geographical regions in six continents. Methods Beta diversity was quantified with four complementary measures: the percentage of singletons (species occurring at only one site), Whittake’s beta diversity (β(W)), a directional beta diversity metric based on the correlation in species occurrences among spatially contiguous sites (β(R2)), and a multivariate abundance-based metric (β(MV)). We used linear modelling to quantify the relationships between these metrics of beta diversity and geographic, climatic, and soil variables. Results Soil fertility and variability in temperature and rainfall, and to a lesser extent latitude, were the most important environmental predictors of beta diversity. Metrics related to species identity (percentage of singletons and β(W)) were most sensitive to soil fertility, whereas those metrics related to environmental gradients and abundance ((β(R2)) and β(MV)) were more associated with climate variability. Interactions among soil variables, climatic factors, and plant cover were not important determinants of beta diversity. Sites receiving less than 178 mm of annual rainfall differed sharply in species composition from more mesic sites (> 200 mm). Main conclusions Soil fertility and variability in temperature and rainfall are the most important environmental predictors of variation in plant beta diversity in global drylands. Our results suggest that those sites annually receiving ~ 178 mm of rainfall will be especially sensitive to future climate changes. These findings may help to define appropriate conservation strategies for mitigating effects of climate change on dryland vegetation. PMID:25914437

Beta lactam antibiotics residues in cow's milk: comparison of efficacy of three screening tests used in Bosnia and Herzegovina.

PubMed

Fejzic, Nihad; Begagic, Muris; Šerić-Haračić, Sabina; Smajlovic, Muhamed

2014-08-27

Beta lactam antibiotics are widely used in therapy of cattle, particularly for the treatment of mastitis.  Over 95% of residue testing in dairies in Bosnia and Herzegovina is for Beta lactams. The aim of this paper is to compare the efficacy of three most common screening tests for Beta lactam residues in cow's milk in our country. The tests used in the study are SNAP β Lactam test (Idexx), Rosa Charm β Lactam test and Inhibition MRL test. Study samples included: standardized concentrations of penicillin solution (0, 2, 3, 4, 5 and 6 ppb). In addition we tested milk samples from three equal size study groups (not receiving any antibiotic therapy, treated with Beta lactams for mastitis and treated with Beta lactams for diseases other than mastitis). Sensitivity and specificity were determined for each test, using standard penicillin concentrations with threshold value set at concentration of 4 ppb (Maximum residue level - MLR). Additionally we determined proportions of presumably false negative and false positive results for each test using results of filed samples testing. Agreement of test results for each test pair was assessed through Kappa coefficients interpreted by Landis-Koch scale. Detection level of all tests was shown to be well below MRL. This alongside with effects of natural inhibitors in milk contributed to finding of positive results in untreated and treated animals after the withholding period. Screening tests for beta lactam residues are important tools for ensuring that milk for human consumption is free from antibiotics residues.

Beta lactam antibiotics residues in cow’s milk: comparison of efficacy of three screening tests used in Bosnia and Herzegovina

PubMed Central

Fejzić, Nihad; Begagić, Muris; Šerić-Haračić, Sabina; Smajlović, Muhamed

2014-01-01

Beta lactam antibiotics are widely used in therapy of cattle, particularly for the treatment of mastitis. Over 95% of residue testing in dairies in Bosnia and Herzegovina is for Beta lactams. The aim of this paper is to compare the efficacy of three most common screening tests for Beta lactam residues in cow’s milk in our country. The tests used in the study are SNAP β Lactam test (Idexx), Rosa Charm β Lactam test (Charm Sciences) and Inhibition MRL test (A&M). Study samples included: standardized concentrations of penicillin solution (0, 2, 3, 4, 5 and 6 ppb). In addition we tested milk samples from three equal size study groups (not receiving any antibiotic therapy, treated with Beta lactams for mastitis and treated with Beta lactams for diseases other than mastitis). Sensitivity and specificity were determined for each test, using standard penicillin concentrations with threshold value set at concentration of 4 ppb (Maximum residue level – MLR). Additionally we determined proportions of presumably false negative and false positive results for each test using results of filed samples testing. Agreement of test results for each test pair was assessed through Kappa coefficients interpreted by Landis-Koch scale. Detection level of all tests was shown to be well below MRL. This alongside with effects of natural inhibitors in milk contributed to finding of positive results in untreated and treated animals after the withholding period. Screening tests for beta lactam residues are important tools for ensuring that milk for human consumption is free from antibiotics residues. PMID:25172975

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

Meeks, Kelsey; Pantoya, Michelle L.; Green, Micah

For dispersions containing a single type of particle, it has been observed that the onset of percolation coincides with a critical value of volume fraction. When the volume fraction is calculated based on excluded volume, this critical percolation threshold is nearly invariant to particle shape. The critical threshold has been calculated to high precision for simple geometries using Monte Carlo simulations, but this method is slow at best, and infeasible for complex geometries. This article explores an analytical approach to the prediction of percolation threshold in polydisperse mixtures. Specifically, this paper suggests an extension of the concept of excluded volume,more » and applies that extension to the 2D binary disk system. The simple analytical expression obtained is compared to Monte Carlo results from the literature. In conclusion, the result may be computed extremely rapidly and matches key parameters closely enough to be useful for composite material design.« less

Putting Beta-Diversity on the Map: Broad-Scale Congruence and Coincidence in the Extremes

PubMed Central

McKnight, Meghan W; White, Peter S; McDonald, Robert I; Lamoreux, John F; Sechrest, Wes; Ridgely, Robert S; Stuart, Simon N

2007-01-01

Beta-diversity, the change in species composition between places, is a critical but poorly understood component of biological diversity. Patterns of beta-diversity provide information central to many ecological and evolutionary questions, as well as to conservation planning. Yet beta-diversity is rarely studied across large extents, and the degree of similarity of patterns among taxa at such scales remains untested. To our knowledge, this is the first broad-scale analysis of cross-taxon congruence in beta-diversity, and introduces a new method to map beta-diversity continuously across regions. Congruence between amphibian, bird, and mammal beta-diversity in the Western Hemisphere varies with both geographic location and spatial extent. We demonstrate that areas of high beta-diversity for the three taxa largely coincide, but areas of low beta-diversity exhibit little overlap. These findings suggest that similar processes lead to high levels of differentiation in amphibian, bird, and mammal assemblages, while the ecological and biogeographic factors influencing homogeneity in vertebrate assemblages vary. Knowledge of beta-diversity congruence can help formulate hypotheses about the mechanisms governing regional diversity patterns and should inform conservation, especially as threat from global climate change increases. PMID:17927449

Serum concentrations of vitamin A and oxidative stress in critically ill patients with sepsis.

PubMed

Ribeiro Nogueira, C; Ramalho, A; Lameu, E; Da Silva Franca, C A; David, C; Accioly, E

2009-01-01

Sepsis is one of the main causes of mortality in patients in Intensive Care Units. As a result of the systemic inflammatory response and of the decrease of the aerobic metabolism in sepsis, the oxidative stress occurs. Vitamin A is recognized by the favorable effect that it exerts on the immune response to infections and antioxidant action. To bring new elements for reviewing of the nutritional support addressed to critically ill patients with sepsis, with emphasis to vitamin A. Critically ill patients with sepsis had circulating concentrations of retinol, beta-carotene, thiobarbituric acid-reactive substances (TBARS) and C-reactive protein (CRP) measured in Medicosurgical Intensive Care Unit in the city of Rio de Janeiro, Brazil. The patients were divided into two groups: patients who were receiving nutritional support and those without support. At the act of the patient's admission, APACHE II score was calculated. 46 patients were studied (with diet n = 24 and without diet n = 22). Reduced levels of retinol and beta-carotene were found in 65.2% and 73.9% of the patients, respectively. Among the patients who presented lower concentrations of CRP it was found higher beta-carotene inadequacy (64.8%) and 50% of retinol inadequacy. There was no significant difference as regards retinol, TBARS and APACHE II levels among the patients with and without nutritional support. However, higher levels of CRP (p = 0.001) and lower levels of serum beta-carotene (p = 0.047) were found in patients without nutritional support. Septic patients presented an important inadequacy of retinol and beta-carotene. The present study bring elements to the elaboration/review of the nutritional protocol directed to the group studied, especially as regards vitamin A intake.

Prolonged noise exposure-induced auditory threshold shifts in rats

PubMed Central

Chen, Guang-Di; Decker, Brandon; Muthaiah, Vijaya Prakash Krishnan; Sheppard, Adam; Salvi, Richard

2014-01-01

Noise-induced hearing loss (NIHL) initially increases with exposure duration, but eventually reaches an asymptotic threshold shift (ATS) once the exposure duration exceeds 18-24 h. Equations for predicting the ATS have been developed for several species, but not for rats, even though this species is extensively used in noise exposure research. To fill this void, we exposed rats to narrowband noise (NBN, 16-20 kHz) for 5 weeks starting at 80 dB SPL in the first week and then increasing the level by 6 dB per week to a final level of 104 dB SPL. Auditory brainstem responses (ABR) were recorded before, during, and following the exposure to determine the amount of hearing loss. The noise induced threshold shift to continuous long-term exposure, defined as compound threshold shift (CTS), within and above 16-20 kHz increased with noise level at the rate of 1.82 dB threshold shift per dB of noise level (NL) above a critical level (C) of 77.2 dB SPL i.e. CTS = 1.82(NL-77.2). The normalized amplitude of the largest ABR peak measured at 100 dB SPL decreased at the rate of 3.1% per dB of NL above the critical level of 76.9 dB SPL, i.e., %ABR Reduction = 3.1%(NL-76.9). ABR thresholds measured >30 days post-exposure only partially recovered resulting in a permanent threshold shift of 30-40 dB along with severe hair cell loss in the basal, high-frequency region of the cochlea. In the rat, CTS increases with noise level with a slope similar to humans and chinchillas. The critical level (C) in the rat is similar to that of humans, but higher than that of chinchillas. PMID:25219503

c-Ski inhibits the TGF-beta signaling pathway through stabilization of inactive Smad complexes on Smad-binding elements.

PubMed

Suzuki, Hiroyuki; Yagi, Ken; Kondo, Miki; Kato, Mitsuyasu; Miyazono, Kohei; Miyazawa, Keiji

2004-06-24

c-Ski inhibits transforming growth factor-beta (TGF-beta) signaling through interaction with Smad proteins. c-Ski represses Smad-mediated transcriptional activation, probably through its action as a transcriptional co-repressor. c-Ski also inhibits TGF-beta-induced downregulation of genes such as c-myc. However, mechanisms for transcriptional regulation of target genes by c-Ski have not been fully determined. In this study, we examined how c-Ski inhibits both TGF-beta-induced transcriptional activation and repression. DNA-affinity precipitation analysis revealed that c-Ski enhances the binding of Smad2 and 4, and to a lesser extent Smad3, to both CAGA and TGF-beta1 inhibitory element probes. A c-Ski mutant, which is unable to interact with Smad4, failed to enhance the binding of Smad complex on these probes and to inhibit the Smad-responsive promoter. These results suggest that stabilization of inactive Smad complexes on DNA is a critical event in c-Ski-mediated inhibition of TGF-beta signaling.

Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice.

PubMed

Sherman, Maxwell A; Lee, Shane; Law, Robert; Haegens, Saskia; Thorn, Catherine A; Hämäläinen, Matti S; Moore, Christopher I; Jones, Stephanie R

2016-08-16

Human neocortical 15-29-Hz beta oscillations are strong predictors of perceptual and motor performance. However, the mechanistic origin of beta in vivo is unknown, hindering understanding of its functional role. Combining human magnetoencephalography (MEG), computational modeling, and laminar recordings in animals, we present a new theory that accounts for the origin of spontaneous neocortical beta. In our MEG data, spontaneous beta activity from somatosensory and frontal cortex emerged as noncontinuous beta events typically lasting <150 ms with a stereotypical waveform. Computational modeling uniquely designed to infer the electrical currents underlying these signals showed that beta events could emerge from the integration of nearly synchronous bursts of excitatory synaptic drive targeting proximal and distal dendrites of pyramidal neurons, where the defining feature of a beta event was a strong distal drive that lasted one beta period (∼50 ms). This beta mechanism rigorously accounted for the beta event profiles; several other mechanisms did not. The spatial location of synaptic drive in the model to supragranular and infragranular layers was critical to the emergence of beta events and led to the prediction that beta events should be associated with a specific laminar current profile. Laminar recordings in somatosensory neocortex from anesthetized mice and awake monkeys supported these predictions, suggesting this beta mechanism is conserved across species and recording modalities. These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function.

Measurement of the proton $$A_1$$ and $$A_2$$ spin asymmetries. Probing Color Forces

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

Armstrong, Whitney

The Spin Asymmetries of the Nucleon Experiment (SANE) measured the proton spin structure functionmore » $$g_2$$ in a range of Bjorken x, 0.3 < x < 0.8, where extraction of the twist-3 matrix element $$d_2^p$$ (an integral of $$g_2$$ weighted by $x^2$) is most sensitive. The data was taken from $Q^2$ equal to 2.5 $GeV^2$ up to 6.5 $GeV^2$. In this polarized electron scattering off a polarized hydrogen target experiment, two double spin asymmetries, A∥ and A⊥ were measured using the BETA (Big Electron Telescope Array) Detector. BETA consisted of a scintillator hodoscope, gas Cerenkov counter, lucite hodoscope and a large lead glass electromagnetic calorimeter. With a unique open geometry, a threshold gas Cerenkov detector allowed BETA to cleanly identify electrons for this inclusive experiment. A measurement of $$d_2^p$$ is compared to lattice QCD calculations.« less

High frequency fishbone driven by passing energetic ions in tokamak plasmas

DOE PAGES

Wang, Feng; Yu, L. M.; Fu, G. Y.; ...

2017-03-22

High frequency fishbone instability driven by passing energetic ions was first reported in the Princeton beta experiment with tangential neutral-beam-injection (Heidbrink et al 1986 Phys. Rev. Lett. 57 835–8). It could play an important role for ITER-like burning plasmas, where α particles are mostly passing particles. In this work, a generalized energetic ion distribution function and finite drift orbit width effect are considered to improve the theoretical model for passing particle driving fishbone instability. For purely passing energetic ions with zero drift orbit width, the kinetic energymore » $$\\delta {{W}_{k}}$$ is derived analytically. The derived analytic expression is more accurate as compared to the result of previous work. For a generalized energetic ion distribution function, the fishbone dispersion relation is derived and is solved numerically. As a result, numerical results show that broad and off-axis beam density profiles can significantly increase the beam ion beta threshold $${{\\beta}_{c}}$$ for instability and decrease mode frequency.« less

Measurement of the temperature-dependent threshold shear-stress of red blood cell aggregation.

PubMed

Lim, Hyun-Jung; Nam, Jeong-Hun; Lee, Yong-Jin; Shin, Sehyun

2009-09-01

Red blood cell (RBC) aggregation is becoming an important hemorheological parameter, which typically exhibits temperature dependence. Quite recently, a critical shear-stress was proposed as a new dimensional index to represent the aggregative and disaggregative behaviors of RBCs. The present study investigated the effect of the temperature on the critical shear-stress that is required to keep RBC aggregates dispersed. The critical shear-stress was measured at various temperatures (4, 10, 20, 30, and 37 degrees C) through the use of a transient microfluidic aggregometry. The critical shear-stress significantly increased as the blood temperature lowered, which accorded with the increase in the low-shear blood viscosity with the lowering of the temperature. Furthermore, the critical shear-stress also showed good agreement with the threshold shear-stress, as measured in a rotational Couette flow. These findings assist in rheologically validating the critical shear-stress, as defined in the microfluidic aggregometry.

Beta-adrenergic signaling promotes tumor angiogenesis and prostate cancer progression through HDAC2-mediated suppression of thrombospondin-1.

PubMed

Hulsurkar, M; Li, Z; Zhang, Y; Li, X; Zheng, D; Li, W

2017-03-01

Chronic behavioral stress and beta-adrenergic signaling have been shown to promote cancer progression, whose underlying mechanisms are largely unclear, especially the involvement of epigenetic regulation. Histone deacetylase-2 (HDAC2), an epigenetic regulator, is critical for stress-induced cardiac hypertrophy. It is unknown whether it is necessary for beta-adrenergic signaling-promoted cancer progression. Using xenograft models, we showed that chronic behavioral stress and beta-adrenergic signaling promote angiogenesis and prostate cancer progression. HDAC2 was induced by beta-adrenergic signaling in vitro and in mouse xenografts. We next uncovered that HDAC2 is a direct target of cAMP response element-binding protein (CREB) that is activated by beta-adrenergic signaling. Notably, HDAC2 is necessary for beta-adrenergic signaling to induce angiogenesis. We further demonstrated that, upon CREB activation, HDAC2 represses thrombospondin-1 (TSP1), a potent angiogenesis inhibitor, through epigenetic regulation. Together, these data establish a novel pathway that HDAC2 and TSP1 act downstream of CREB activation in beta-adrenergic signaling to promote cancer progression.

Phase diagram of the ultrafast photoinduced insulator-metal transition in vanadium dioxide

NASA Astrophysics Data System (ADS)

Cocker, T. L.; Titova, L. V.; Fourmaux, S.; Holloway, G.; Bandulet, H.-C.; Brassard, D.; Kieffer, J.-C.; El Khakani, M. A.; Hegmann, F. A.

2012-04-01

We use time-resolved terahertz spectroscopy to probe the ultrafast dynamics of the insulator-metal phase transition induced by femtosecond laser pulses in a nanogranular vanadium dioxide (VO2) film. Based on the observed thresholds for characteristic transient terahertz dynamics, a phase diagram of critical pump fluence versus temperature for the insulator-metal phase transition in VO2 is established for the first time over a broad range of temperatures down to 17 K. We find that both Mott and Peierls mechanisms are present in the insulating state and that the photoinduced transition is nonthermal. We propose a critical-threshold model for the ultrafast photoinduced transition based on a critical density of electrons and a critical density of coherently excited phonons necessary for the structural transition to the metallic state. As a result, evidence is found at low temperatures for an intermediate metallic state wherein the Mott state is melted but the Peierls distortion remains intact, consistent with recent theoretical predictions. Finally, the observed terahertz conductivity dynamics above the photoinduced transition threshold reveal nucleation and growth of metallic nanodomains over picosecond time scales.

Impact of organizational infrastructure on beta-blocker and aspirin therapy for acute myocardial infarction.

PubMed

Ellerbeck, Edward F; Bhimaraj, Arvind; Hall, Sandra

2006-09-01

Although organizational change has been advocated as a critical component of quality improvement, there is little data available on the variation and effectiveness of organizational elements in the care of acute myocardial infarction (AMI). This study was designed to examine the impact of organizational infrastructure on the use of aspirin and beta-blockers during and after AMI. We assessed organizational infrastructure for AMI care in 44 hospitals in Kansas and linked these data to patient-specific process of care data collected in Kansas as part of the Cooperative Cardiovascular Project. While controlling for clustering within hospitals, we examined the relationships between hospital infrastructure and use of aspirin and beta-blocker both at admission and discharge. Hospitals varied widely in their inclusion of aspirin and beta-blockers in AMI pathways, protocols, and standardized order sets. Hospitals also varied in the involvement of their physicians in AMI quality improvement and in their ability to identify a physician champion for AMI care. Patients were more likely to receive aspirin on admission in hospitals that included aspirin in their emergency department order sets (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.01-2.48) and were more likely to receive beta-blockers on admission and at discharge if beta-blockers were included in an emergency department protocol or pathway (OR 2.14, 95% CI 1.25-3.77 and OR 3.5, 95% CI 1.14-14.38, respectively). Use of beta-blockers at discharge was also associated with commitment of administration to AMI care and the presence of a physician champion. Quality improvement efforts should include a close examination of the organization of AMI care to assure that critical elements in the care of AMI patients are not inadvertently omitted.

Effects of transcranial direct current stimulation on pain, mood and serum endorphin level in the treatment of fibromyalgia: A double blinded, randomized clinical trial.

PubMed

Khedr, Eman M; Omran, Eman A H; Ismail, Nadia M; El-Hammady, Dina H; Goma, Samar H; Kotb, Hassan; Galal, Hannan; Osman, Ayman M; Farghaly, Hannan S M; Karim, Ahmed A; Ahmed, Gehad A

Recent studies have shown that novel neuro-modulating techniques can have pain-relieving effects in the treatment of chronic pain. The aim of this work is to evaluate the effects of transcranial direct current stimulation (tDCS) in relieving fibromyalgia pain and its relation with beta-endorphin changes. Forty eligible patients with primary fibromyalgia were randomized to receive real anodal tDCS or sham tDCS of the left motor cortex (M1) daily for 10 days. Each patient was evaluated using widespread pain index (WPI), symptom severity of fibromyalgia (SS), visual analogue scale (VAS), and determination of pain threshold as a primary outcome. Hamilton depression and anxiety scales (HAM-D and HAM-A) and estimation of serum beta-endorphin level pre and post-sessions were used as secondary outcome. All rating scales were conducted at the baseline, after the 5th, 10th session, 15 days and 1 month after the end of the sessions. Eighteen patients from each group completed the follow-up schedule with no significant difference between them regarding the duration of illness or the baseline scales. A significant TIME × GROUP interaction for each rating scale (WPI, SS, VAS, pain threshold, HAM-A, HAM-D) indicated that the effect of treatment differed in the two groups with higher improvement in the experimental scores of the patients in the real tDCS group (P = 0.001 for WPI, SS, VAS, pain threshold, and 0.002, 0.03 for HAM-A, HAM-D respectively). Negative correlations between changes in serum beta-endorphin level and the changes in different rating scales were found (P = 0.003, 0.003, 0.05, 0.002, 0002 for WPI, SS, VAS, HAM-A, and HAM-D respectively). Ten sessions of real tDCS over M1 can induce pain relief and mood improvement in patients with fibromyalgia, which were found to be related to changes in serum endorphin levels. ClinicalTrials.gov Identifier: NCT02704611. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of glutamine 17 of the bovine papillomavirus E5 protein in platelet-derived growth factor beta receptor activation and cell transformation.

PubMed

Klein, O; Polack, G W; Surti, T; Kegler-Ebo, D; Smith, S O; DiMaio, D

1998-11-01

The bovine papillomavirus E5 protein is a small, homodimeric transmembrane protein that forms a stable complex with the cellular platelet-derived growth factor (PDGF) beta receptor through transmembrane and juxtamembrane interactions, resulting in receptor activation and cell transformation. Glutamine 17 in the transmembrane domain of the 44-amino-acid E5 protein is critical for complex formation and receptor activation, and we previously proposed that glutamine 17 forms a hydrogen bond with threonine 513 of the PDGF beta receptor. We have constructed and analyzed mutant E5 proteins containing all possible amino acids at position 17 and examined the ability of these proteins to transform C127 fibroblasts, which express endogenous PDGF beta receptor. Although several position 17 mutants were able to transform cells, mutants containing amino acids with side groups that were unable to participate in hydrogen bonding interactions did not form a stable complex with the PDGF beta receptor or transform cells, in agreement with the proposed interaction between position 17 of the E5 protein and threonine 513 of the receptor. The nature of the residue at position 17 also affected the ability of the E5 proteins to dimerize. Overall, there was an excellent correlation between the ability of the various E5 mutant proteins to bind the PDGF beta receptor, lead to receptor tyrosine phosphorylation, and transform cells. Similar results were obtained in Ba/F3 hematopoietic cells expressing exogenous PDGF beta receptor. In addition, treatment of E5-transformed cells with a specific inhibitor of the PDGF receptor tyrosine kinase reversed the transformed phenotype. These results confirm the central importance of the PDGF beta receptor in mediating E5 transformation and highlight the critical role of the residue at position 17 of the E5 protein in the productive interaction with the PDGF beta receptor. On the basis of molecular modeling analysis and the known chemical properties of the amino acids, we suggest a structural basis for the role of the residue at position 17 in E5 dimerization and in complex formation between the E5 protein and the PDGF beta receptor.

Fear conditioning is associated with altered integration of PLC and ERK signaling in the hippocampus.

PubMed

Buckley, Colin T; Caldwell, Kevin K

2004-12-01

The extracellular signal-regulated protein kinases (ERKs) are proline-directed, serine/threonine kinases that regulate a variety of cellular functions, including proliferation, differentiation, and plasticity. In the present report, we provide evidence that ERK2 and phosphatidylinositol-specific phospholipase C (PLC)-beta and -gamma isozymes interact in the rat hippocampal formation. We found that anti-PLC-beta1a, -beta2, -beta4, -gamma1 and -gamma2, but not -beta3, immune complexes isolated from rat hippocampal formation postnuclear fractions contain anti-ERK2 immunoreactivity. Further, we show that PLC catalytic activity is associated with anti-ERK2 immunoprecipitates isolated from the hippocampal formation, and that the amount of enzyme activity is significantly increased following fear-conditioned learning. The observed interactions may be mediated by consensus sequences conforming to an ERK2 docking site, termed a D-domain, that we identified in PLC-beta1a, -beta2, -beta4 -gamma1 and -gamma2. Based on these results, we propose that PLC-beta and PLC-gamma isozymes form signaling complexes with ERK2 in rat brain, and these complexes play critical roles in learning and memory, as well as a variety of other neuronal functions.

An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation

NASA Technical Reports Server (NTRS)

Wikramanayake, Athula H.; Hong, Melanie; Lee, Patricia N.; Pang, Kevin; Byrum, Christine A.; Bince, Joanna M.; Xu, Ronghui; Martindale, Mark Q.

2003-01-01

The human oncogene beta-catenin is a bifunctional protein with critical roles in both cell adhesion and transcriptional regulation in the Wnt pathway. Wnt/beta-catenin signalling has been implicated in developmental processes as diverse as elaboration of embryonic polarity, formation of germ layers, neural patterning, spindle orientation and gap junction communication, but the ancestral function of beta-catenin remains unclear. In many animal embryos, activation of beta-catenin signalling occurs in blastomeres that mark the site of gastrulation and endomesoderm formation, raising the possibility that asymmetric activation of beta-catenin signalling specified embryonic polarity and segregated germ layers in the common ancestor of bilaterally symmetrical animals. To test whether nuclear translocation of beta-catenin is involved in axial identity and/or germ layer formation in 'pre-bilaterians', we examined the in vivo distribution, stability and function of beta-catenin protein in embryos of the sea anemone Nematostella vectensis (Cnidaria, Anthozoa). Here we show that N. vectensis beta-catenin is differentially stabilized along the oral-aboral axis, translocated into nuclei in cells at the site of gastrulation and used to specify entoderm, indicating an evolutionarily ancient role for this protein in early pattern formation.

Using Smartphones to Monitor Bipolar Disorder Symptoms: A Pilot Study.

PubMed

Beiwinkel, Till; Kindermann, Sally; Maier, Andreas; Kerl, Christopher; Moock, Jörn; Barbian, Guido; Rössler, Wulf

2016-01-06

Relapse prevention in bipolar disorder can be improved by monitoring symptoms in patients' daily life. Smartphone apps are easy-to-use, low-cost tools that can be used to assess this information. To date, few studies have examined the usefulness of smartphone data for monitoring symptoms in bipolar disorder. We present results from a pilot test of a smartphone-based monitoring system, Social Information Monitoring for Patients with Bipolar Affective Disorder (SIMBA), that tracked daily mood, physical activity, and social communication in 13 patients. The objective of this study was to investigate whether smartphone measurements predicted clinical symptoms levels and clinical symptom change. The hypotheses that smartphone measurements are (1) negatively related to clinical depressive symptoms and (2) positively related to clinical manic symptoms were tested. Clinical rating scales were administered to assess clinical depressive and manic symptoms. Patients used a smartphone with the monitoring app for up to 12 months. Random-coefficient multilevel models were computed to analyze the relationship between smartphone data and externally rated manic and depressive symptoms. Overall clinical symptom levels and clinical symptom changes were predicted by separating between-patient and within-patient effects. Using established clinical thresholds from the literature, marginal effect plots displayed clinical relevance of smartphone data. Overall symptom levels and change in clinical symptoms were related to smartphone measures. Higher overall levels of clinical depressive symptoms were predicted by lower self-reported mood measured by the smartphone (beta=-.56, P<.001). An increase in clinical depressive symptoms was predicted by a decline in social communication (ie, outgoing text messages: beta=-.28, P<.001) and a decline in physical activity as measured by the smartphone (ie, cell tower movements: beta=-.11, P=.03). Higher overall levels of clinical manic symptoms were predicted by lower physical activity on the smartphone (ie, distance travelled: beta=-.37, P<.001), and higher social communication (beta=.48, P=.03). An increase in clinical manic symptoms was predicted by a decrease in physical activity on the smartphone (beta=-.17, P<.001). Clinical symptoms were related to some objective and subjective smartphone measurements, but not all smartphone measures predicted the occurrence of bipolar symptoms above clinical thresholds. Thus, smartphones have the potential to monitor bipolar disorder symptoms in patients' daily life. Further validation of monitoring tools in a larger sample is needed. Conclusions are limited by the low prevalence of manic and depressive symptoms in the study sample. International Standard Randomized Controlled Trial Number (ISRCTN): 05663421; http://www.controlled-trials.com/ISRCTN05663421 (Archived by WebCite at http://www.webcitation.org/6d9wsibJB).

Ignition criterion for heterogeneous energetic materials based on hotspot size-temperature threshold

NASA Astrophysics Data System (ADS)

Barua, A.; Kim, S.; Horie, Y.; Zhou, M.

2013-02-01

A criterion for the ignition of granular explosives (GXs) and polymer-bonded explosives (PBXs) under shock and non-shock loading is developed. The formulation is based on integration of a quantification of the distributions of the sizes and locations of hotspots in loading events using a cohesive finite element method (CFEM) developed recently and the characterization by Tarver et al. [C. M. Tarver et al., "Critical conditions for impact- and shock-induced hot spots in solid explosives," J. Phys. Chem. 100, 5794-5799 (1996)] of the critical size-temperature threshold of hotspots required for chemical ignition of solid explosives. The criterion, along with the CFEM capability to quantify the thermal-mechanical behavior of GXs and PBXs, allows the critical impact velocity for ignition, time to ignition, and critical input energy at ignition to be determined as functions of material composition, microstructure, and loading conditions. The applicability of the relation between the critical input energy (E) and impact velocity of James [H. R. James, "An extension to the critical energy criterion used to predict shock initiation thresholds," Propellants, Explos., Pyrotech. 21, 8-13 (1996)] for shock loading is examined, leading to a modified interpretation, which is sensitive to microstructure and loading condition. As an application, numerical studies are undertaken to evaluate the ignition threshold of granular high melting point eXplosive, octahydro-1,3,5,7-tetranitro-1,2,3,5-tetrazocine (HMX) and HMX/Estane PBX under loading with impact velocities up to 350 ms-1 and strain rates up to 105 s-1. Results show that, for the GX, the time to criticality (tc) is strongly influenced by initial porosity, but is insensitive to grain size. Analyses also lead to a quantification of the differences between the responses of the GXs and PBXs in terms of critical impact velocity for ignition, time to ignition, and critical input energy at ignition. Since the framework permits explicit tracking of the influences of microstructure, loading, and mechanical constraints, the calculations also show the effects of stress wave reflection and confinement condition on the ignition behaviors of GXs and PBXs.

Critical Mutation Rate Has an Exponential Dependence on Population Size in Haploid and Diploid Populations

PubMed Central

Aston, Elizabeth; Channon, Alastair; Day, Charles; Knight, Christopher G.

2013-01-01

Understanding the effect of population size on the key parameters of evolution is particularly important for populations nearing extinction. There are evolutionary pressures to evolve sequences that are both fit and robust. At high mutation rates, individuals with greater mutational robustness can outcompete those with higher fitness. This is survival-of-the-flattest, and has been observed in digital organisms, theoretically, in simulated RNA evolution, and in RNA viruses. We introduce an algorithmic method capable of determining the relationship between population size, the critical mutation rate at which individuals with greater robustness to mutation are favoured over individuals with greater fitness, and the error threshold. Verification for this method is provided against analytical models for the error threshold. We show that the critical mutation rate for increasing haploid population sizes can be approximated by an exponential function, with much lower mutation rates tolerated by small populations. This is in contrast to previous studies which identified that critical mutation rate was independent of population size. The algorithm is extended to diploid populations in a system modelled on the biological process of meiosis. The results confirm that the relationship remains exponential, but show that both the critical mutation rate and error threshold are lower for diploids, rather than higher as might have been expected. Analyzing the transition from critical mutation rate to error threshold provides an improved definition of critical mutation rate. Natural populations with their numbers in decline can be expected to lose genetic material in line with the exponential model, accelerating and potentially irreversibly advancing their decline, and this could potentially affect extinction, recovery and population management strategy. The effect of population size is particularly strong in small populations with 100 individuals or less; the exponential model has significant potential in aiding population management to prevent local (and global) extinction events. PMID:24386200

Polynomial sequences for bond percolation critical thresholds

DOE PAGES

Scullard, Christian R.

2011-09-22

In this paper, I compute the inhomogeneous (multi-probability) bond critical surfaces for the (4, 6, 12) and (3 4, 6) using the linearity approximation described in (Scullard and Ziff, J. Stat. Mech. 03021), implemented as a branching process of lattices. I find the estimates for the bond percolation thresholds, pc(4, 6, 12) = 0.69377849... and p c(3 4, 6) = 0.43437077..., compared with Parviainen’s numerical results of p c = 0.69373383... and p c = 0.43430621... . These deviations are of the order 10 -5, as is standard for this method. Deriving thresholds in this way for a given latticemore » leads to a polynomial with integer coefficients, the root in [0, 1] of which gives the estimate for the bond threshold and I show how the method can be refined, leading to a series of higher order polynomials making predictions that likely converge to the exact answer. Finally, I discuss how this fact hints that for certain graphs, such as the kagome lattice, the exact bond threshold may not be the root of any polynomial with integer coefficients.« less

Administration of IL-1beta to the 4th ventricle causes anorexia that is blocked by agouti-related peptide and that coincides with activation of tyrosine-hydroxylase neurons in the nucleus of the solitary tract.

PubMed

DeBoer, Mark D; Scarlett, Jarrad M; Levasseur, Peter R; Grant, Wilmon F; Marks, Daniel L

2009-02-01

Inflammation-associated cachexia is associated with multiple chronic diseases and involves activation of appetite regulating centers in the arcuate nucleus of the hypothalamus (ARH). The nucleus of the solitary tract (NTS) in the brainstem has also been implicated as an important nucleus involved in appetite regulation. We set out to determine whether the NTS may be involved in inflammation-associated anorexia by injecting IL-1 beta into the 4th ventricle and assessing food intake and NTS neuronal activation. Injection of IL-1 beta produced a decrease in food intake at 3 and 12h after injection which was ameliorated at the 12h time point by a sub-threshold dose of agouti-related peptide (AgRP). Investigation into neuron types in the NTS revealed that IL-1 beta injection was associated with an increase in c-Fos activity in NTS neurons expressing tyrosine hydroxylase (TH). Additionally, injection of IL-1 beta into the 4th ventricle did not produce c-Fos activation of neurons expressing pro-opiomelanocortin (POMC) in the ARH, cells known to be involved in producing anorexia in response to systemic inflammation. Double-label in situ hybridization revealed that TH neurons did not express IL-1 receptor I (IL1-RI) transcript, demonstrating that c-Fos activation of TH neurons in this setting was not via direct stimulation of IL-1 beta on TH neurons themselves. We conclude that IL-1 beta injection into the 4th ventricle produces anorexia and is accompanied by an increase in activation in TH neurons in the NTS. This provides evidence that the brainstem may be an important mediator of anorexia in the setting of inflammation.

Synthesis and antiviral activity of 3'-deoxy-3'-C-hydroxymethyl nucleosides.

PubMed

Bamford, M J; Coe, P L; Walker, R T

1990-09-01

A series of 3'-branched-chain sugar nucleosides, in particular 3'-deoxy-3'-C-hydroxmethyl nucleosides, have been synthesized and evaluated as antiviral agents. Reaction of 1-(2,3-epoxy-5-O-trityl-beta-D-lyxo-pentofuranosyl) derivatives 12 and 13, of uracil and thymine, respectively, with 5,6-dihydro-2-lithio-5-methyl-1,3,5-dithiazine 14 afforded the corresponding 3'-functionalized nucleosides 15 and 16, respectively. Replacement of the trityl group with tertbutyldiphenylsilyl allowed high yielding hydrolysis of the 3'-function to give the 3'-deoxy-3'-C-formyl-beta-D-arabino-pentofuranosyl nucleosides 21 and 22. Desilylation afforded the 1-(3-deoxy-3-C-formyl-beta- D-lyxo-pentofuranosyl) 3',5'-O-hemiacetal nucleosides 33 and 34, respectively. Reduction of the formyl group of 21 and 22, followed by desilylation, yielded the 3'-deoxy-3'-C-(hydroxymethyl)-beta-D-arabino- pentofuranosyl) analogues 7 and 8, respectively. The uracil base moiety of 7 was converted to 5-iodouracil and then to (E)-5-(2-bromovinyl)uracil to furnish an analogue 10 of BVaraU. The 1-(3-deoxy-3-C-(hydroxymethyl)-beta-D-lyxo-pentofuranosyl) and 1-(2,3-dideoxy-3-C-(hydroxymethyl)-beta-D-erythro-pentofuranosyl) derivatives of uracil (31 and 6, respectively) and 5-iodouracil (32 and 9, respectively) were also obtained. All novel, fully deprotected nucleoside analogues were evaluated for antiviral activity against human immunodeficiency virus type-1, herpes simplex virus types-1 and -2, varicella zoster virus, human cytomegalovirus and influenza A. Of the compounds tested only (E)-5-(2-bromovinyl)-1-[3-deoxy- 3-C-(hydroxymethyl)-beta-D-arabino-pentofuranosyl]uracil (10) inhibited VZV (alone), but did so at concentrations well below the cytotoxicity threshold.

Using a higher criticism statistic to detect modest effects in a genome-wide study of rheumatoid arthritis

PubMed Central

2009-01-01

In high-dimensional studies such as genome-wide association studies, the correction for multiple testing in order to control total type I error results in decreased power to detect modest effects. We present a new analytical approach based on the higher criticism statistic that allows identification of the presence of modest effects. We apply our method to the genome-wide study of rheumatoid arthritis provided in the Genetic Analysis Workshop 16 Problem 1 data set. There is evidence for unknown bias in this study that could be explained by the presence of undetected modest effects. We compared the asymptotic and empirical thresholds for the higher criticism statistic. Using the asymptotic threshold we detected the presence of modest effects genome-wide. We also detected modest effects using 90th percentile of the empirical null distribution as a threshold; however, there is no such evidence when the 95th and 99th percentiles were used. While the higher criticism method suggests that there is some evidence for modest effects, interpreting individual single-nucleotide polymorphisms with significant higher criticism statistics is of undermined value. The goal of higher criticism is to alert the researcher that genetic effects remain to be discovered and to promote the use of more targeted and powerful studies to detect the remaining effects. PMID:20018032

TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

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

Chung, Eun Jee; Chun, Ji Na; Jung, Sun-Ah

2011-11-18

Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology inmore » pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases.« less

Existence of infinitely many stationary solutions of the L2-subcritical and critical NLSE on compact metric graphs

NASA Astrophysics Data System (ADS)

Dovetta, Simone

2018-04-01

We investigate the existence of stationary solutions for the nonlinear Schrödinger equation on compact metric graphs. In the L2-subcritical setting, we prove the existence of an infinite number of such solutions, for every value of the mass. In the critical regime, the existence of infinitely many solutions is established if the mass is lower than a threshold value, while global minimizers of the NLS energy exist if and only if the mass is lower or equal to the threshold. Moreover, the relation between this threshold and the topology of the graph is characterized. The investigation is based on variational techniques and some new versions of Gagliardo-Nirenberg inequalities.

Resolution of the threshold fracture energy paradox for solid particle erosion

NASA Astrophysics Data System (ADS)

Peck, Daniel; Volkov, Grigory; Mishuris, Gennady; Petrov, Yuri

2016-12-01

Previous models of a single erosion impact, for a rigid axisymmetric indenter defined by the shape function ?, have shown that a critical shape parameter ? exists which determines the behaviour of the threshold fracture energy. However, repeated investigations into this parameter have found no physical explanation for its value. Again utilising the notion of incubation time prior to fracture, this paper attempts to provide a physical explanation of this phenomena by introducing a supersonic stage into the model. The final scheme allows for the effect of waves along the indenters contact area to be taken into account. The effect of this physical characteristic of the impact on the threshold fracture energy and critical shape parameter ? are investigated and discussed.

Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling.

PubMed

Guo, Xing; Ramirez, Alejandro; Waddell, David S; Li, Zhizhong; Liu, Xuedong; Wang, Xiao-Fan

2008-01-01

The broad range of biological responses elicited by transforming growth factor-beta (TGF-beta) in various types of tissues and cells is mainly determined by the expression level and activity of the effector proteins Smad2 and Smad3. It is not fully understood how the baseline properties of Smad3 are regulated, although this molecule is in complex with many other proteins at the steady state. Here we show that nonactivated Smad3, but not Smad2, undergoes proteasome-dependent degradation due to the concerted action of the scaffolding protein Axin and its associated kinase, glycogen synthase kinase 3-beta (GSK3-beta). Smad3 physically interacts with Axin and GSK3-beta only in the absence of TGF-beta. Reduction in the expression or activity of Axin/GSK3-beta leads to increased Smad3 stability and transcriptional activity without affecting TGF-beta receptors or Smad2, whereas overexpression of these proteins promotes Smad3 basal degradation and desensitizes cells to TGF-beta. Mechanistically, Axin facilitates GSK3-beta-mediated phosphorylation of Smad3 at Thr66, which triggers Smad3 ubiquitination and degradation. Thr66 mutants of Smad3 show altered protein stability and hence transcriptional activity. These results indicate that the steady-state stability of Smad3 is an important determinant of cellular sensitivity to TGF-beta, and suggest a new function of the Axin/GSK3-beta complex in modulating critical TGF-beta/Smad3-regulated processes during development and tumor progression.

The reactor antineutrino anomaly and low energy threshold neutrino experiments

NASA Astrophysics Data System (ADS)

Cañas, B. C.; Garcés, E. A.; Miranda, O. G.; Parada, A.

2018-01-01

Short distance reactor antineutrino experiments measure an antineutrino spectrum a few percent lower than expected from theoretical predictions. In this work we study the potential of low energy threshold reactor experiments in the context of a light sterile neutrino signal. We discuss the perspectives of the recently detected coherent elastic neutrino-nucleus scattering in future reactor antineutrino experiments. We find that the expectations to improve the current constraints on the mixing with sterile neutrinos are promising. We also analyze the measurements of antineutrino scattering off electrons from short distance reactor experiments. In this case, the statistics is not competitive with inverse beta decay experiments, although future experiments might play a role when compare it with the Gallium anomaly.

Inhibition of Transforming Growth Factor-Beta1 SignalingAttenuates Ataxia Telangiectasia Mutated Activity in Response toGenotoxic Stress

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

Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose

2006-01-01

Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta} (TGF{beta})-1, which is activated by radiation, is a potent and pleiotropic mediator of physiologic and pathologic processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}I null murine epithelial cells or human epithelial cells treated with a small-molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17, and p53; reduced H2AX radiation-induced foci; and increased radiosensitivity compared with TGF{beta} competent cells.more » We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM, which directs epithelial cell stress responses, cell fate, and tissue integrity. Thus, Tgf{beta}I, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.« less

A Matter of Millimeters: Defining the Processes for Critical Clearances on Curiosity

NASA Technical Reports Server (NTRS)

Florow, Brandon

2013-01-01

The Mars Science Laboratory (MSL) mission presents an immense packaging problem in that it takes a rover the size of a car with a sky crane landing system and packs it tightly into a spacecraft. This creates many areas of close and critical clearances. Critical Clearances are defined as hardware-to-hardware or hardware-to-envelope clearances which fall below a pre-established location dependent threshold and pose a risk of hardware to hardware contact during events such as launch, entry, landing, and operations. Close Clearances, on the other hand, are defined as any clearance value that is chosen to be tracked but is larger than the critical clearance threshold for its region. Close clearances may be tracked for various reasons including uncertainty in design, large expected dynamic motion, etc.

Cyclooxygenase system contributes to the maintenance of post convulsive period of epileptic phenomena in the genetically epileptic El mice.

PubMed

Okada, Kazumasa; Yamashita, Uki; Tsuji, Sadatoshi

2006-09-01

Recent studies have shown that cytokines and cyclooxygenase (COX)-2 are up-regulated in the brain of human epilepsy patients and animal models of epilepsy. We investigated the effect of inflammatory responses induced by intramuscular injection of turpentine on the epileptic phenomenon in genetically epileptic El mice. As parameters of epileptic seizure, seizure threshold (number of toss-ups to induce convulsion), duration of actual convulsion and duration of post actual convulsive period (period from the offset of convulsion to full recovery) were evaluated. The post actual convulsive period was prolonged without any change of seizure threshold or duration of actual convulsion 24 h after turpentine injection. Although pretreatment with indomethacin for one week did not change the seizure parameters, indomethacin suppressed the prolongation of the post actual convulsive period induced by turpentine. The mRNA expression of IL-1beta, IL-6 and COX-2 in the cerebral cortex was detected by RT-PCR. There was no difference in the mRNA expression in the cerebral cortex before and 24 h after seizure. The mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex were up-regulated 24 h after turpentine injection. On the other hand, the up-regulated mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex after turpentine treatment were not suppressed by indomethacin. These results suggest that prostaglandins induced with COX-2 in the cerebral cortex seem to play an important role in the maintenance of the post convulsive period, but not in induction and maintenance of the actual convulsive state.

Observation of Alpha-Driven TAEs in TFTR

NASA Astrophysics Data System (ADS)

Nazikian, R.; Chang, Z.; Fu, G. Y.; Majeski, R.; Batha, S.; Bell, M.; Budny, R.; Cheng, C. Z.; Darrow, D. S.; Duong, H.; Efthimion, P. C.; Fredrickson, E.; Levinton, F.; Mazzucato, E.; Medley, S.; Taylor, S.; Zweben, G.

1996-11-01

Transient mode activity in the TAE range of frequencies (150-170 kHz) with toroidal mode numbers n=2,3 is observed in reduced magnetic shear DT discharges on TFTR with a fusion power threshold of ~1.5 MW. Mode activity appears 50-100 msec after NBI in discharges with the following machine parameter: B=5.3 T, I=1.6MA, R=260cm, P_NBI=25-28 MW, q(0)>2.0 from MSE and toroidal beta β_T<1%. The elevated q(0) and reduced central shear |s|<0.2 is achieved using a full size plasma startup with delayed NBI. Theoretical calculations using NOVA-K indicate that the combined effect of low shear, low beta and elevated q(0) leads to a very low instability threshold for the alpha-driven TAE with β_α (0) ~ 10-4. This appears to be consistent with experimental observations of mode activity in DT plasmas with β_α ~ 10-4 (determined from TRANSP analysis). Thus far the modes have only been observed on Mirnov coils with fluctuation levels tildeB ~ 1mG. Efforts to determine mode location by perturbing the edge density and inducing strong toroidal velocity shear will be reported, as will efforts to affect mode stability by systematically varying the central safety factor.

Neutrino physics with DARWIN

NASA Astrophysics Data System (ADS)

Benabderrahmane, M. L.

2017-09-01

DARWIN (DARk matter WImp search with liquid xenoN) will be a multi-ton dark matter detector with the primary goal of exploring the entire experimentally accessible parameter space for weakly interacting massive particles (WIMPs) over a wide mass-range. With its 40 tonne active liquid xenon target, low-energy threshold and ultra-low background level, DARWIN can also search for other rare interactions. Here we present its sensitivity to low-energy solar neutrinos and to neutrinoless double beta decay. In a low-energy window of 2-30 keV a rate of 105/year, from pp and 7Be neutrinos can be reached. Such a measurement, with 1% precision will allow testing neutrinos models. DARWIN could also reach a competitive half-life sensitivity of 8.5 · 1027 y to the neutrinoless double beta decay (0νββ) of 136Xe after an exposure of 140 t×y of natural xenon. Nuclear recoils from coherent scattering of solar neutrinos will limit the sensitivity to WIMP masses below 5 GeV/c2, and the event rate from 8B neutrinos would range from a few to a few tens of events per tonne and year, depending on the energy threshold of the detector. Deviations from the predicted but yet unmeasured neutrino flux would be an indication for physics beyond the Standard Model

Site- and bond-percolation thresholds in K_{n,n}-based lattices: Vulnerability of quantum annealers to random qubit and coupler failures on chimera topologies.

PubMed

Melchert, O; Katzgraber, Helmut G; Novotny, M A

2016-04-01

We estimate the critical thresholds of bond and site percolation on nonplanar, effectively two-dimensional graphs with chimeralike topology. The building blocks of these graphs are complete and symmetric bipartite subgraphs of size 2n, referred to as K_{n,n} graphs. For the numerical simulations we use an efficient union-find-based algorithm and employ a finite-size scaling analysis to obtain the critical properties for both bond and site percolation. We report the respective percolation thresholds for different sizes of the bipartite subgraph and verify that the associated universality class is that of standard two-dimensional percolation. For the canonical chimera graph used in the D-Wave Systems Inc. quantum annealer (n=4), we discuss device failure in terms of network vulnerability, i.e., we determine the critical fraction of qubits and couplers that can be absent due to random failures prior to losing large-scale connectivity throughout the device.

Simple Model for Identifying Critical Regions in Atrial Fibrillation

NASA Astrophysics Data System (ADS)

Christensen, Kim; Manani, Kishan A.; Peters, Nicholas S.

2015-01-01

Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wave front propagation on an anisotropic structure mimicking the branching network of heart muscle cells. This integration of phenomenological dynamics and pertinent structure shows how AF emerges spontaneously when the transverse cell-to-cell coupling decreases, as occurs with age, beyond a threshold value. We identify critical regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allows us to calculate analytically the risk of arrhythmia and express the threshold value of transversal cell-to-cell coupling as a function of the model parameters. This threshold value decreases with increasing refractory period by reducing the number of critical regions which can initiate and sustain microreentrant circuits. These biologically testable predictions might inform ablation therapies and arrhythmic risk assessment.

Deconfinement and the Hagedorn transition in string theory.

PubMed

Chaudhuri, S

2001-03-05

We introduce a new definition of the thermal partition function in string theory. With this new definition, the thermal partition functions of all of the string theories obey thermal duality relations with self-dual Hagedorn temperature beta(2)(H) = 4pi(2)alpha('). A beta-->beta(2)(H)/beta transformation maps the type I theory into a new string theory (type I) with thermal D p-branes, spatial hypersurfaces supporting a p-dimensional finite temperature non-Abelian Higgs-gauge theory for p< or =9. We demonstrate a continuous phase transition in the behavior of the static heavy quark-antiquark potential for small separations r(2)(*)

Higher criticism thresholding: Optimal feature selection when useful features are rare and weak.

PubMed

Donoho, David; Jin, Jiashun

2008-09-30

In important application fields today-genomics and proteomics are examples-selecting a small subset of useful features is crucial for success of Linear Classification Analysis. We study feature selection by thresholding of feature Z-scores and introduce a principle of threshold selection, based on the notion of higher criticism (HC). For i = 1, 2, ..., p, let pi(i) denote the two-sided P-value associated with the ith feature Z-score and pi((i)) denote the ith order statistic of the collection of P-values. The HC threshold is the absolute Z-score corresponding to the P-value maximizing the HC objective (i/p - pi((i)))/sqrt{i/p(1-i/p)}. We consider a rare/weak (RW) feature model, where the fraction of useful features is small and the useful features are each too weak to be of much use on their own. HC thresholding (HCT) has interesting behavior in this setting, with an intimate link between maximizing the HC objective and minimizing the error rate of the designed classifier, and very different behavior from popular threshold selection procedures such as false discovery rate thresholding (FDRT). In the most challenging RW settings, HCT uses an unconventionally low threshold; this keeps the missed-feature detection rate under better control than FDRT and yields a classifier with improved misclassification performance. Replacing cross-validated threshold selection in the popular Shrunken Centroid classifier with the computationally less expensive and simpler HCT reduces the variance of the selected threshold and the error rate of the constructed classifier. Results on standard real datasets and in asymptotic theory confirm the advantages of HCT.

Higher criticism thresholding: Optimal feature selection when useful features are rare and weak

PubMed Central

Donoho, David; Jin, Jiashun

2008-01-01

In important application fields today—genomics and proteomics are examples—selecting a small subset of useful features is crucial for success of Linear Classification Analysis. We study feature selection by thresholding of feature Z-scores and introduce a principle of threshold selection, based on the notion of higher criticism (HC). For i = 1, 2, …, p, let πi denote the two-sided P-value associated with the ith feature Z-score and π(i) denote the ith order statistic of the collection of P-values. The HC threshold is the absolute Z-score corresponding to the P-value maximizing the HC objective (i/p − π(i))/i/p(1−i/p). We consider a rare/weak (RW) feature model, where the fraction of useful features is small and the useful features are each too weak to be of much use on their own. HC thresholding (HCT) has interesting behavior in this setting, with an intimate link between maximizing the HC objective and minimizing the error rate of the designed classifier, and very different behavior from popular threshold selection procedures such as false discovery rate thresholding (FDRT). In the most challenging RW settings, HCT uses an unconventionally low threshold; this keeps the missed-feature detection rate under better control than FDRT and yields a classifier with improved misclassification performance. Replacing cross-validated threshold selection in the popular Shrunken Centroid classifier with the computationally less expensive and simpler HCT reduces the variance of the selected threshold and the error rate of the constructed classifier. Results on standard real datasets and in asymptotic theory confirm the advantages of HCT. PMID:18815365

Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics.

PubMed

Majiduddin, Fahd K; Palzkill, Timothy

2003-03-01

Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases. Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these beta-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo.

PubMed

Gautam, Dinesh; Han, Sung-Jun; Hamdan, Fadi F; Jeon, Jongrye; Li, Bo; Li, Jian Hua; Cui, Yinghong; Mears, David; Lu, Huiyan; Deng, Chuxia; Heard, Thomas; Wess, Jürgen

2006-06-01

One of the hallmarks of type 2 diabetes is that pancreatic beta cells fail to release sufficient amounts of insulin in the presence of elevated blood glucose levels. Insulin secretion is modulated by many hormones and neurotransmitters including acetylcholine, the major neurotransmitter of the peripheral parasympathetic nervous system. The physiological role of muscarinic acetylcholine receptors expressed by pancreatic beta cells remains unclear at present. Here, we demonstrate that mutant mice selectively lacking the M3 muscarinic acetylcholine receptor subtype in pancreatic beta cells display impaired glucose tolerance and greatly reduced insulin release. In contrast, transgenic mice selectively overexpressing M3 receptors in pancreatic beta cells show a profound increase in glucose tolerance and insulin release. Moreover, these mutant mice are resistant to diet-induced glucose intolerance and hyperglycemia. These findings indicate that beta cell M3 muscarinic receptors play a key role in maintaining proper insulin release and glucose homeostasis.

c-Ski, Smurf2, and Arkadia as regulators of TGF-beta signaling: new targets for managing myofibroblast function and cardiac fibrosis.

PubMed

Cunnington, Ryan H; Nazari, Mansoreh; Dixon, Ian M C

2009-10-01

Recent studies demonstrate the critical role of the extracellular matrix in the organization of parenchymal cells in the heart. Thus, an understanding of the modes of regulation of matrix production by cardiac myofibroblasts is essential. Transforming growth factor beta (TGF-beta) signaling is transduced through the canonical Smad pathway, and the involvement of this pathway in matrix synthesis and other processes requires precise control. Inhibition of Smad signaling may be achieved at the receptor level through the targeting of the TGF-beta type I receptors with an inhibitory Smad7/Smurf2 complex, or at the transcriptional level through c-Ski/receptor-Smad/co-mediator Smad4 interactions. Conversely, Arkadia protein intensifies TGF-beta-induced effects by marking c-Ski and inhibitory Smad7 for destruction. The study of these TGF-beta mediators is essential for future treatment of fibrotic disease, and this review highlights recent relevant findings that may impact our understanding of cardiac fibrosis.

A critical concentration of N-terminal pyroglutamylated amyloid beta drives the misfolding of Ab1-42 into more toxic aggregates.

PubMed

Galante, Denise; Ruggeri, Francesco Simone; Dietler, Giovanni; Pellistri, Francesca; Gatta, Elena; Corsaro, Alessandro; Florio, Tullio; Perico, Angelo; D'Arrigo, Cristina

2016-10-01

A wide consensus based on robust experimental evidence indicates pyroglutamylated amyloid-β isoform (AβpE3-42) as one of the most neurotoxic peptides involved in the onset of Alzheimer's disease. Furthermore, AβpE3-42 co-oligomerized with excess of Aβ1-42, produces oligomers and aggregates that are structurally distinct and far more cytotoxic than those made from Aβ1-42 alone. Here, we investigate quantitatively the influence of AβpE3-42 on biophysical properties and biological activity of Aβ1-42. We tested different ratios of AβpE3-42/Aβ1-42 mixtures finding a correlation between the biological activity and the structural conformation and morphology of the analyzed mixtures. We find that a mixture containing 5% AβpE3-42, induces the highest disruption of intracellular calcium homeostasis and the highest neuronal toxicity. These data correlate to an high content of relaxed antiparallel β-sheet structure and the coexistence of a population of big spheroidal aggregates together with short fibrils. Our experiments provide also evidence that AβpE3-42 causes template-induced misfolding of Aβ1-42 at ratios below 33%. This means that there exists a critical concentration required to have seeding on Aβ1-42 aggregation, above this threshold, the seed effect is not possible anymore and AβpE3-42 controls the total aggregation kinetics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical factors determine olfactory system beta oscillations in waking rats.

PubMed

Lowry, Catherine A; Kay, Leslie M

2007-07-01

Recent studies have pointed to olfactory system beta oscillations of the local field potential (15-30 Hz) and their roles both in learning and as specific responses to predator odors. To describe odorant physical properties, resultant behavioral responses and changes in the central olfactory system that may induce these oscillations without associative learning, we tested rats with 26 monomolecular odorants spanning 6 log units of theoretical vapor pressure (estimate of relative vapor phase concentration) and 10 different odor mixtures. We found odorant vapor phase concentration to be inversely correlated with investigation time on the first presentation, after which investigation times were brief and not different across odorants. Analysis of local field potentials from the olfactory bulb and anterior piriform cortex shows that beta oscillations in waking rats occur specifically in response to the class of volatile organic compounds with vapor pressures of 1-120 mmHg. Beta oscillations develop over the first three to four presentations and are weakly present for some odorants in anesthetized rats. Gamma oscillations show a smaller effect that is not restricted to the same range of odorants. Olfactory bulb theta oscillations were also examined as a measure of effective afferent input strength, and the power of these oscillations did not vary systematically with vapor pressure, suggesting that it is not olfactory bulb drive strength that determines the presence of beta oscillations. Theta band coherence analysis shows that coupling strength between the olfactory bulb and piriform cortex increases linearly with vapor phase concentration, which may facilitate beta oscillations above a threshold.

9.4 COMPLEX SYSTEM THEORY AND THE TRANSDIAGNOSTIC USE OF EARLY WARNING SIGNALS TO FORESEE THE TYPE OF FUTURE TRANSITIONS IN SYMPTOMS

PubMed Central

Wichers, Marieke; Schreuder, Marieke; Hartman, Catharina; Wigman, Hanneke

2018-01-01

Abstract Background Recently, we showed that assumptions from complex system theory seem applicable in the field of psychiatry. This means that indicators of critical slowing down in the system signal the risk for a critical transition in the near future. In the current study we wanted to explore whether the principle of critical slowing down may also be informative to anticipate on the type of symptoms that individuals are most likely to develop. This is relevant as it may lead to personalized prediction of risk of whether adolescents with mixed complaints are most likely to develop either depression, anxiety, somatic or psychotic symptoms in the near future. For example, we hypothesized that critical slowing down in feeling ‘suspicious’ more strongly indicates risk for a future transition to psychotic symptoms, while critical slowing down in feeling ‘down’ more strongly indicates risk for a transition to depressive symptoms. Methods We examined this in a population of adolescents (most between 15 and 18 years) as adolescents are an at-risk group for the development of psychopathology. At baseline experience sampling was performed for 6 days, 10 measurements a day. Affect items were used to assess autocorrelation as an indicator of ‘critical slowing down’ of the system. At baseline and follow-up SCL-90 questionnaires were administered. In total, 147 adolescents participated both in baseline and follow-up measures and showed increases in at least one of the defined symptom dimensions. We examined whether autocorrelation was positively associated with the size of symptom transition and whether different type of transitions (in depression, anxiety etc.) were differentially predicted by autocorrelations in specific affect states. Results The analyses were done very recently, and findings have not been presented before. We found both shared and specific indicators of risk in the development for transition to various symptom dimensions. First, autocorrelation in ‘feeling suspicious’ appeared to be the strongest signal for all assessed psychopathology dimensions (SCL-90 depression: std beta: 0.185; p <0.001; SCL-90 anxiety: std beta: 0.093; p=0.006; SCL-90 interpersonal sensitivity: std beta: 0.176, p<0.001). Second, we found that the combination of ‘feeling suspicious’ and the affect with the second-highest autocorrelation together predicted the precise type of symptom transition. Thus, the combination of feeling suspicious (std beta: 0.185; p<0.001) and down (std beta: 0.108; p=0.001) predicted larger increases in depressive symptoms one year later on the SCL-90, while the combination of feeling suspicious (std beta: 0.093; p=0.006) with feeling anxious (std beta: 0.086; p=0.014) predicted larger increases in anxiety symptoms a year later on the SCL-90. Discussion These findings support the hypothesis that indicators of slowing down can not only be used to predict risk for a mean level shift in symptoms, but that they can also be informative for the type of symptom transitions at hand. In a next step these findings could be translated to designs measuring personalized early warnings for future direction of symptom shifts, and if successful to clinical implementation of these techniques.

Achieving a long-lived high-beta plasma state by energetic beam injection

NASA Astrophysics Data System (ADS)

Guo, H. Y.; Binderbauer, M. W.; Tajima, T.; Milroy, R. D.; Steinhauer, L. C.; Yang, X.; Garate, E. G.; Gota, H.; Korepanov, S.; Necas, A.; Roche, T.; Smirnov, A.; Trask, E.

2015-04-01

Developing a stable plasma state with high-beta (ratio of plasma to magnetic pressures) is of critical importance for an economic magnetic fusion reactor. At the forefront of this endeavour is the field-reversed configuration. Here we demonstrate the kinetic stabilizing effect of fast ions on a disruptive magneto-hydrodynamic instability, known as a tilt mode, which poses a central obstacle to further field-reversed configuration development, by energetic beam injection. This technique, combined with the synergistic effect of active plasma boundary control, enables a fully stable ultra-high-beta (approaching 100%) plasma with a long lifetime.

Role of estrogen receptors alpha, beta and GPER1/GPR30 in pancreatic beta-cells.

PubMed

Nadal, Angel; Alonso-Magdalena, Paloma; Soriano, Sergi; Ripoll, Cristina; Fuentes, Esther; Quesada, Ivan; Ropero, Ana Belen

2011-01-01

Estrogen receptors (ER) are emerging as important molecules involved in the adaptation of beta-cells to insulin resistance. The onset of type 2 diabetes is marked by insulin secretory dysfunction and decreased beta-cell mass. During pregnancy, puberty and obesity there is increased metabolic demand and insulin resistance is developed. This metabolic state increases the demand on beta-cells to augment insulin biosynthesis and release. In this respect, ERalpha is directly implicated in the E2-regulation of insulin content and secretion, while ERbeta is in the E2-potentiation of glucose-induced insulin release. Both receptors develop their actions within the physiological range of E2. In addition, the G protein-coupled estrogen receptor (GPER1/GPR30) seems to be implicated in the E2-regulation of stimulus-secretion coupling in the three cell types of the islet. The increased demand of insulin production for long time may lead to beta-cell stress and apoptosis. ERalpha, ERbeta and GPER1/GPR30 are involved in preventing beta-cell apoptosis, impeding the loss of critical beta-cell mass. Therefore, estrogen receptors may play an essential role in the adaptation of the pancreas to insulin resistant periods.

Heterocellular interaction enhances recruitment of {alpha} and {beta}-catenins and ZO-2 into functional gap-junction complexes and induces gap junction-dependant differentiation of mammary epithelial cells

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

Talhouk, Rabih S.; Mroue, Rana; Mokalled, Mayssa

2008-11-01

Gap junctions (GJ) are required for mammary epithelial differentiation. Using epithelial (SCp2) and myoepithelial-like (SCg6) mouse-derived mammary cells, the role of heterocellular interaction in assembly of GJ complexes and functional differentiation ({beta}-casein expression) was evaluated. Heterocellular interaction is critical for {beta}-casein expression, independent of exogenous basement membrane or cell anchoring substrata. Functional differentiation of SCp2, co-cultured with SCg6, is more sensitive to GJ inhibition relative to homocellular SCp2 cultures differentiated by exogenous basement membrane. Connexin (Cx)32 and Cx43 levels were not regulated across culture conditions; however, GJ functionality was enhanced under differentiation-permissive conditions. Immunoprecipitation studies demonstrated association of junctional complexmore » components ({alpha}-catenin, {beta}-catenin and ZO-2) with Cx32 and Cx43, in differentiation conditions, and additionally with Cx30 in heterocellular cultures. Although {beta}-catenin did not shuttle between cadherin and GJ complexes, increased association between connexins and {beta}-catenin in heterocellular cultures was observed. This was concomitant with reduced nuclear {beta}-catenin, suggesting that differentiation in heterocellular cultures involves sequestration of {beta}-catenin in GJ complexes.« less

hCG, the wonder of today's science

PubMed Central

2012-01-01

Background hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail. Content These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies. Conclusions The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death. PMID:22455390

To bloom or not to bloom: contrasting responses of cyanobacteria to recent heat waves explained by critical thresholds of abiotic drivers.

PubMed

Huber, Veronika; Wagner, Carola; Gerten, Dieter; Adrian, Rita

2012-05-01

Past heat waves are considered harbingers of future climate change. In this study, we have evaluated the effects of two recent Central European summer heat waves (2003 and 2006) on cyanobacterial blooms in a eutrophic, shallow lake. While a bloom of cyanobacteria developed in 2006, consistent with our expectations, cyanobacterial biomass surprisingly remained at a record-low during the entire summer of 2003. Critical thresholds of abiotic drivers extracted from the long-term (1993-2007) data set of the studied lake using classification tree analysis (CTA) proved suitable to explain these observations. We found that cyanobacterial blooms were especially favoured in 2006 because thermal stratification was critically intense (Schmidt stability >44 g cm cm(-2)) and long-lasting (>3 weeks). Our results also suggest that some cyanobacterial species (Anabaena sp.) benefitted directly from the stable water column, whereas other species (Planktothrix sp.) took advantage of stratification-induced internal nutrient loading. In 2003, conditions were less favourable for cyanobacteria due to a spell of lower temperatures and stronger winds in mid-summer; as a result, the identified thresholds of thermal stratification were hardly ever reached. Overall, our study shows that extracting critical thresholds of environmental drivers from long-term records is a promising avenue for predicting ecosystem responses to future climate warming. Specifically, our results emphasize that not average temperature increase but changes in short-term meteorological variability will determine whether cyanobacteria will bloom more often in a warmer world.

Three-dimensional periodic dielectric structures having photonic Dirac points

DOEpatents

Bravo-Abad, Jorge; Joannopoulos, John D.; Soljacic, Marin

2015-06-02

The dielectric, three-dimensional photonic materials disclosed herein feature Dirac-like dispersion in quasi-two-dimensional systems. Embodiments include a face-centered cubic (fcc) structure formed by alternating layers of dielectric rods and dielectric slabs patterned with holes on respective triangular lattices. This fcc structure also includes a defect layer, which may comprise either dielectric rods or a dielectric slab with patterned with holes. This defect layer introduces Dirac cone dispersion into the fcc structure's photonic band structure. Examples of these fcc structures enable enhancement of the spontaneous emission coupling efficiency (the .beta.-factor) over large areas, contrary to the conventional wisdom that the .beta.-factor degrades as the system's size increases. These results enable large-area, low-threshold lasers; single-photon sources; quantum information processing devices; and energy harvesting systems.

Discrete diffraction managed solitons: Threshold phenomena and rapid decay for general nonlinearities

NASA Astrophysics Data System (ADS)

Choi, Mi-Ran; Hundertmark, Dirk; Lee, Young-Ran

2017-10-01

We prove a threshold phenomenon for the existence/non-existence of energy minimizing solitary solutions of the diffraction management equation for strictly positive and zero average diffraction. Our methods allow for a large class of nonlinearities; they are, for example, allowed to change sign, and the weakest possible condition, it only has to be locally integrable, on the local diffraction profile. The solutions are found as minimizers of a nonlinear and nonlocal variational problem which is translation invariant. There exists a critical threshold λcr such that minimizers for this variational problem exist if their power is bigger than λcr and no minimizers exist with power less than the critical threshold. We also give simple criteria for the finiteness and strict positivity of the critical threshold. Our proof of existence of minimizers is rather direct and avoids the use of Lions' concentration compactness argument. Furthermore, we give precise quantitative lower bounds on the exponential decay rate of the diffraction management solitons, which confirm the physical heuristic prediction for the asymptotic decay rate. Moreover, for ground state solutions, these bounds give a quantitative lower bound for the divergence of the exponential decay rate in the limit of vanishing average diffraction. For zero average diffraction, we prove quantitative bounds which show that the solitons decay much faster than exponentially. Our results considerably extend and strengthen the results of Hundertmark and Lee [J. Nonlinear Sci. 22, 1-38 (2012) and Commun. Math. Phys. 309(1), 1-21 (2012)].

Line length dependence of threshold current density and driving force in eutectic SnPb and SnAgCu solder electromigration

NASA Astrophysics Data System (ADS)

Yoon, Min-Seung; Ko, Min-Ku; Kim, Bit-Na; Kim, Byung-Joon; Park, Yong-Bae; Joo, Young-Chang

2008-04-01

The relationship between the threshold current density and the critical line length in eutectic SnPb and SnAgCu electromigrations were examined using solder lines with the various lengths ranging from 100to1000μm. When the electron wind-force was balanced by the back-stress gradient force, the net flux of electromigration is zero, at which the current density and line length are defined as the threshold current density and the critical length, respectively. It was found that in SnAgCu electromigration, the 1/L dependence on the threshold current density showed good agreement, whereas the threshold current densities of the eutectic SnPb deviated from the 1/L dependence. The balance between the electron wind-force and the back-stress gradient force was the main factor determining the threshold product of SnAgCu electromigration. On the other hand, in the case of eutectic SnPb, the chemical driving force is contributed as a back-flux force in addition to the back-stress gradient force. The existence of the chemical driving force was caused by the nonequilibrium Pb concentration inside the Pb-rich phases between the cathode and anode during the electromigration procedure.

Regulation of pancreatic islet beta-cell mass by growth factor and hormone signaling.

PubMed

Huang, Yao; Chang, Yongchang

2014-01-01

Dysfunction and destruction of pancreatic islet beta cells is a hallmark of diabetes. Better understanding of cellular signals in beta cells will allow development of therapeutic strategies for diabetes, such as preservation and expansion of beta-cell mass and improvement of beta-cell function. During the past several decades, the number of studies analyzing the molecular mechanisms, including growth factor/hormone signaling pathways that impact islet beta-cell mass and function, has increased exponentially. Notably, somatolactogenic hormones including growth hormone (GH), prolactin (PRL), and insulin-like growth factor-1 (IGF-1) and their receptors (GHR, PRLR, and IGF-1R) are critically involved in beta-cell growth, survival, differentiation, and insulin secretion. In this chapter, we focus more narrowly on GH, PRL, and IGF-1 signaling, and GH-IGF-1 cross talk. We also discuss how these signaling aspects contribute to the regulation of beta-cell proliferation and apoptosis. In particular, our novel findings of GH-induced formation of GHR-JAK2-IGF-1R protein complex and synergistic effects of GH and IGF-1 on beta-cell signaling, proliferation, and antiapoptosis lead to a new concept that IGF-1R may serve as a proximal component of GH/GHR signaling. © 2014 Elsevier Inc. All rights reserved.

beta-Arrestin 2: a Negative Regulator of Inflammatory Responses in Polymorphonuclear Leukocytes.

PubMed

Basher, Fahmin; Fan, Hongkuan; Zingarelli, Basilia; Borg, Keith T; Luttrell, Lou M; Tempel, George E; Halushka, Perry V; Cook, James A

2008-01-01

Heterotrimeric Gi proteins have been previously implicated in signaling leading to inflammatory mediator production induced by bacterial lipopolysaccharide (LPS). beta-arrestins are ubiquitously expressed proteins that alter G-protein-coupled receptors signaling. beta-arrestin 2 plays a multifaceted role as a scaffold protein in regulating cellular inflammatory responses. Polymorphonuclear leukocytes (PMNs) activated by LPS induce inflammatory responses resulting in organ injury during sepsis. We hypothesized that beta-arrestin 2 is a critical modulator of inflammatory responses in PMNs. To examine the potential role of beta-arrestin 2 in LPS-induced cellular activation, we studied homozygous beta-arrestin 2 (-/-), heterozygous (+/-), and wildtype (+/+) mice. PMNs were stimulated with LPS for 16h. There was increased basal TNFalpha and IL-6 production in the beta-arrestin 2 (-/-) compared to both beta-arrestin 2 (+/-) and (+/+) cells. LPS failed to stimulate TNFalpha production in the beta-arrestin 2 (-/-) PMNs. However, LPS stimulated IL-6 production was increased in the beta-arrestin 2 (-/-) cells compared to (+/+) cells. In subsequent studies, peritoneal PMN recruitment was increased 81% in the beta-arrestin 2 (-/-) mice compared to (+/+) mice (p<0.05). beta-arrestin 2 deficiency resulted in an augmented expression of CD18 and CD62L (p<0.05). In subsequent studies, beta-arrestin 2 (-/-) and (+/+) mice were subjected to cecal ligation and puncture (CLP) and lung was collected and analyzed for myeloperoxidase activity (MPO) as index of PMNs infiltrate. CLP-induced MPO activity was significantly increased (p<0.05) in the beta-arrestin 2 (-/-) compared to (+/+) mice. These studies demonstrate that beta-arrestin 2 is a negative regulator of PMN activation and pulmomary leukosequestration in response to polymicrobial sepsis.

Mechanisms Underlying Decision-Making as Revealed by Deep-Brain Stimulation in Patients with Parkinson's Disease.

PubMed

Herz, Damian M; Little, Simon; Pedrosa, David J; Tinkhauser, Gerd; Cheeran, Binith; Foltynie, Tom; Bogacz, Rafal; Brown, Peter

2018-04-23

To optimally balance opposing demands of speed and accuracy during decision-making, we must flexibly adapt how much evidence we require before making a choice. Such adjustments in decision thresholds have been linked to the subthalamic nucleus (STN), and therapeutic STN deep-brain stimulation (DBS) has been shown to interfere with this function. Here, we performed continuous as well as closed-loop DBS of the STN while Parkinson's disease patients performed a perceptual decision-making task. Closed-loop STN DBS allowed temporally patterned STN stimulation and simultaneous recordings of STN activity. This revealed that DBS only affected patients' ability to adjust decision thresholds if applied in a specific temporally confined time window during deliberation. Only stimulation in that window diminished the normal slowing of response times that occurred on difficult trials when DBS was turned off. Furthermore, DBS eliminated a relative, time-specific increase in STN beta oscillations and compromised its functional relationship with trial-by-trial adjustments in decision thresholds. Together, these results provide causal evidence that the STN is involved in adjusting decision thresholds in distinct, time-limited processing windows during deliberation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Measurement of the scintillation time spectra and pulse-shape discrimination of low-energy β and nuclear recoils in liquid argon with DEAP-1

DOE PAGES

Amaudruz, P. -A.; Batygov, M.; Beltran, B.; ...

2016-09-17

The DEAP-1 low-background liquid argon detector has been used to measure scintillation pulse shapes of beta decays and nuclear recoil events and to demonstrate the feasibility of pulse-shape discrimination down to an electron-equivalent energy of 20 keV ee. The relative intensities of singlet/triplet states in liquid argon have been measured as a function of energy between 15 and 500 keVee for both beta and nuclear recoils. Using a triple-coincidence tag we find the fraction of beta events that are misidentified as nuclear recoils to be less than 6 x 10 -8 between 43-86 keV ee and that the discrimination parametermore » agrees with a simple analytic model. The discrimination measurement is currently limited by nuclear recoils induced by cosmic-ray generated neutrons, and is expected to improve by operating the detector underground at SNOLAB. The analytic model predicts a beta misidentification fraction of 10 -10 for an electron-equivalent energy threshold of 20 keV ee. This reduction allows for a sensitive search for spin-independent scattering of WIMPs from 1000 kg of liquid argon with a WIMP-nucleon cross-section sensitivity of 10 -46 cm 2.« less

Measurement of the scintillation time spectra and pulse-shape discrimination of low-energy β and nuclear recoils in liquid argon with DEAP-1

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

Amaudruz, P. -A.; Batygov, M.; Beltran, B.

The DEAP-1 low-background liquid argon detector has been used to measure scintillation pulse shapes of beta decays and nuclear recoil events and to demonstrate the feasibility of pulse-shape discrimination down to an electron-equivalent energy of 20 keV ee. The relative intensities of singlet/triplet states in liquid argon have been measured as a function of energy between 15 and 500 keVee for both beta and nuclear recoils. Using a triple-coincidence tag we find the fraction of beta events that are misidentified as nuclear recoils to be less than 6 x 10 -8 between 43-86 keV ee and that the discrimination parametermore » agrees with a simple analytic model. The discrimination measurement is currently limited by nuclear recoils induced by cosmic-ray generated neutrons, and is expected to improve by operating the detector underground at SNOLAB. The analytic model predicts a beta misidentification fraction of 10 -10 for an electron-equivalent energy threshold of 20 keV ee. This reduction allows for a sensitive search for spin-independent scattering of WIMPs from 1000 kg of liquid argon with a WIMP-nucleon cross-section sensitivity of 10 -46 cm 2.« less

Observation of Critical-Gradient Behavior in Alfvén-Eigenmode-Induced Fast-Ion Transport.

PubMed

Collins, C S; Heidbrink, W W; Austin, M E; Kramer, G J; Pace, D C; Petty, C C; Stagner, L; Van Zeeland, M A; White, R B; Zhu, Y B

2016-03-04

Experiments in the DIII-D tokamak show that fast-ion transport suddenly becomes stiff above a critical threshold in the presence of many overlapping small-amplitude Alfvén eigenmodes (AEs). The threshold is phase-space dependent and occurs when particle orbits become stochastic due to resonances with AEs. Above threshold, equilibrium fast-ion density profiles are unchanged despite increased drive, and intermittent fast-ion losses are observed. Fast-ion Dα spectroscopy indicates radially localized transport of the copassing population at radii that correspond to the location of midcore AEs. The observation of stiff fast-ion transport suggests that reduced models can be used to effectively predict alpha profiles, beam ion profiles, and losses to aid in the design of optimized scenarios for future burning plasma devices.

Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6⁺CD4⁺ T Cells.

PubMed

Lafferty, Mark K; Sun, Lingling; Christensen-Quick, Aaron; Lu, Wuyuan; Garzino-Demo, Alfredo

2017-05-16

Chemokine receptor type 6 (CCR6)⁺CD4⁺ T cells are preferentially infected and depleted during HIV disease progression, but are preserved in non-progressors. CCR6 is expressed on a heterogeneous population of memory CD4⁺ T cells that are critical to mucosal immunity. Preferential infection of these cells is associated, in part, with high surface expression of CCR5, CXCR4, and α4β7. In addition, CCR6⁺CD4⁺ T cells harbor elevated levels of integrated viral DNA and high levels of proliferation markers. We have previously shown that the CCR6 ligands MIP-3α and human beta defensins inhibit HIV replication. The inhibition required CCR6 and the induction of APOBEC3G. Here, we further characterize the induction of apolipoprotein B mRNA editing enzyme (APOBEC3G) by human beta defensin 2. Human beta defensin 2 rapidly induces transcriptional induction of APOBEC3G that involves extracellular signal-regulated kinases 1/2 (ERK1/2) activation and the transcription factors NFATc2, NFATc1, and IRF4. We demonstrate that human beta defensin 2 selectively protects primary CCR6⁺CD4⁺ T cells infected with HIV-1. The selective protection of CCR6⁺CD4⁺ T cell subsets may be critical in maintaining mucosal immune function and preventing disease progression.

Forecasting Corrosion of Steel in Concrete Introducing Chloride Threshold Dependence on Steel Potential

NASA Astrophysics Data System (ADS)

Sanchez, Andrea Nathalie

Corrosion initiates in reinforced concrete structures exposed to marine environments when the chloride ion concentration at the surface of an embedded steel reinforcing bar exceeds the chloride corrosion threshold (CT) value. The value of CT is generally assumed to have a conservative fixed value ranging from 0.2% to - 0.5 % of chloride ions by weight of cement. However, extensive experimental investigations confirmed that C T is not a fixed value and that the value of CT depends on many variables. Among those, the potential of passive steel embedded in concrete is a key influential factor on the value of CT and has received little attention in the literature. The phenomenon of a potential-dependent threshold (PDT) permits accounting for corrosion macrocell coupling between active and passive steel assembly components in corrosion forecast models, avoiding overly conservative long-term damage projections and leading to more efficient design. The objectives of this investigation was to 1) expand by a systematic experimental assessment the knowledge and data base on how dependent the chloride threshold is on the potential of the steel embedded in concrete and 2) introduce the chloride threshold dependence on steel potential as an integral part of corrosion-related service life prediction of reinforced concrete structures. Experimental assessments on PDT were found in the literature but for a limited set of conditions. Therefore, experiments were conducted with mortar and concrete specimens and exposed to conditions more representative of the field than those previously available. The experimental results confirmed the presence of the PDT effect and provided supporting information to use a value of -550 mV per decade of Cl- for the cathodic prevention slope betaCT, a critical quantitative input for implementation in a practical model. A refinement of a previous corrosion initiation-propagation model that incorporated PDT in a partially submerged reinforced concrete column in sea water was developed. Corrosion was assumed to start when the chloride corrosion threshold was reached in an active steel zone of a given size, followed by recalculating the potential distribution and update threshold values over the entire system at each time step. Notably, results of this work indicated that when PDT is ignored, as is the case in present forecasting model practice, the corrosion damage prediction can be overly conservative which could lead to structural overdesign or misguided future damage management planning. Implementation of PDT in next-generation models is therefore highly desirable. However, developing a mathematical model that forecasts the corrosion damage of an entire marine structure with a fully implemented PDT module can result in excessive computational complexity. Hence, a provisional simplified approach for incorporating the effect of PDT was developed. The approach uses a correction function to be applied to projections that have been computed using the traditional procedures.

Lesion evidence for a critical role of left posterior but not frontal areas in alpha-beta power decreases during context-driven word production.

PubMed

Piai, Vitória; Rommers, Joost; Knight, Robert T

2017-09-09

Different frequency bands in the electroencephalogram are postulated to support distinct language functions. Studies have suggested that alpha-beta power decreases may index word-retrieval processes. In context-driven word retrieval, participants hear lead-in sentences that either constrain the final word ('He locked the door with the') or not ('She walked in here with the'). The last word is shown as a picture to be named. Previous studies have consistently found alpha-beta power decreases prior to picture onset for constrained relative to unconstrained sentences, localised to the left lateral-temporal and lateral-frontal lobes. However, the relative contribution of temporal versus frontal areas to alpha-beta power decreases is unknown. We recorded the electroencephalogram from patients with stroke lesions encompassing the left lateral-temporal and inferior-parietal regions or left-lateral frontal lobe and from matched controls. Individual participant analyses revealed a behavioural sentence context facilitation effect in all participants, except for in the two patients with extensive lesions to temporal and inferior parietal lobes. We replicated the alpha-beta power decreases prior to picture onset in all participants, except for in the two same patients with extensive posterior lesions. Thus, whereas posterior lesions eliminated the behavioural and oscillatory context effect, frontal lesions did not. Hierarchical clustering analyses of all patients' lesion profiles, and behavioural and electrophysiological effects identified those two patients as having a unique combination of lesion distribution and context effects. These results indicate a critical role for the left lateral-temporal and inferior parietal lobes, but not frontal cortex, in generating the alpha-beta power decreases underlying context-driven word production. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

Suhara, Tadahiro; Kanada-En'yo, Yoshiko

Structures of excited states in {sup 14}C are investigated with a method of {beta}-{gamma} constraint antisymmetrized molecular dynamics in combination with the generator coordinate method. Various excited states with the developed 3{alpha}-cluster core structures are suggested in positive- and negative-parity states. In the positive-parity states, triaxial deformed and linear-chain structures are found to construct excited bands. Interestingly, {sup 10}Be+{alpha} correlation is found in the cluster states above the {sup 10}Be+{alpha} threshold energy.

Correlation between cortical beta power and gait speed is suppressed in a parkinsonian model, but restored by therapeutic deep brain stimulation.

PubMed

Polar, Christian A; Gupta, Rahul; Lehmkuhle, Mark J; Dorval, Alan D

2018-05-30

The motor cortex and subthalamic nucleus (STN) of patients with Parkinson's disease (PD) exhibit abnormally high levels of electrophysiological oscillations in the ~12-35 Hz beta-frequency range. Recent studies have shown that beta is partly carried forward to regulate future motor states in the healthy condition, suggesting that steady state beta power is lower when a sequence of movements occurs in a short period of time, such as during fast gait. However, whether this relationship between beta power and motor states persists upon parkinsonian onset or in response to effective therapy is unclear. Using a 6-hydroxy dopamine (6-OHDA) rat model of PD and a custom-built behavioral and neurophysiological recording system, we aimed to elucidate a better understanding of the mechanisms underlying cortical beta power and PD symptoms. In addition to elevated levels of beta oscillations, we show that parkinsonian onset was accompanied by a decoupling of movement intensity - quantified as gait speed - from cortical beta power. Although subthalamic deep brain stimulation (DBS) reduced general levels of beta oscillations in the cortex of all PD animals, the brain's capacity to regulate steady state levels of beta power as a function of movement intensity was only restored in animals with therapeutic DBS. We propose that, in addition to lowering general levels of cortical beta power, restoring the brain's ability to maintain this inverse relationship is critical for effective symptom suppression. Copyright © 2017. Published by Elsevier Inc.

Uncovering state-dependent relationships in shallow lakes using Bayesian latent variable regression.

PubMed

Vitense, Kelsey; Hanson, Mark A; Herwig, Brian R; Zimmer, Kyle D; Fieberg, John

2018-03-01

Ecosystems sometimes undergo dramatic shifts between contrasting regimes. Shallow lakes, for instance, can transition between two alternative stable states: a clear state dominated by submerged aquatic vegetation and a turbid state dominated by phytoplankton. Theoretical models suggest that critical nutrient thresholds differentiate three lake types: highly resilient clear lakes, lakes that may switch between clear and turbid states following perturbations, and highly resilient turbid lakes. For effective and efficient management of shallow lakes and other systems, managers need tools to identify critical thresholds and state-dependent relationships between driving variables and key system features. Using shallow lakes as a model system for which alternative stable states have been demonstrated, we developed an integrated framework using Bayesian latent variable regression (BLR) to classify lake states, identify critical total phosphorus (TP) thresholds, and estimate steady state relationships between TP and chlorophyll a (chl a) using cross-sectional data. We evaluated the method using data simulated from a stochastic differential equation model and compared its performance to k-means clustering with regression (KMR). We also applied the framework to data comprising 130 shallow lakes. For simulated data sets, BLR had high state classification rates (median/mean accuracy >97%) and accurately estimated TP thresholds and state-dependent TP-chl a relationships. Classification and estimation improved with increasing sample size and decreasing noise levels. Compared to KMR, BLR had higher classification rates and better approximated the TP-chl a steady state relationships and TP thresholds. We fit the BLR model to three different years of empirical shallow lake data, and managers can use the estimated bifurcation diagrams to prioritize lakes for management according to their proximity to thresholds and chance of successful rehabilitation. Our model improves upon previous methods for shallow lakes because it allows classification and regression to occur simultaneously and inform one another, directly estimates TP thresholds and the uncertainty associated with thresholds and state classifications, and enables meaningful constraints to be built into models. The BLR framework is broadly applicable to other ecosystems known to exhibit alternative stable states in which regression can be used to establish relationships between driving variables and state variables. © 2017 by the Ecological Society of America.

Threshold-based segmentation of fluorescent and chromogenic images of microglia, astrocytes and oligodendrocytes in FIJI.

PubMed

Healy, Sinead; McMahon, Jill; Owens, Peter; Dockery, Peter; FitzGerald, Una

2018-02-01

Image segmentation is often imperfect, particularly in complex image sets such z-stack micrographs of slice cultures and there is a need for sufficient details of parameters used in quantitative image analysis to allow independent repeatability and appraisal. For the first time, we have critically evaluated, quantified and validated the performance of different segmentation methodologies using z-stack images of ex vivo glial cells. The BioVoxxel toolbox plugin, available in FIJI, was used to measure the relative quality, accuracy, specificity and sensitivity of 16 global and 9 local threshold automatic thresholding algorithms. Automatic thresholding yields improved binary representation of glial cells compared with the conventional user-chosen single threshold approach for confocal z-stacks acquired from ex vivo slice cultures. The performance of threshold algorithms varies considerably in quality, specificity, accuracy and sensitivity with entropy-based thresholds scoring highest for fluorescent staining. We have used the BioVoxxel toolbox to correctly and consistently select the best automated threshold algorithm to segment z-projected images of ex vivo glial cells for downstream digital image analysis and to define segmentation quality. The automated OLIG2 cell count was validated using stereology. As image segmentation and feature extraction can quite critically affect the performance of successive steps in the image analysis workflow, it is becoming increasingly necessary to consider the quality of digital segmenting methodologies. Here, we have applied, validated and extended an existing performance-check methodology in the BioVoxxel toolbox to z-projected images of ex vivo glia cells. Copyright © 2017 Elsevier B.V. All rights reserved.

The ventilatory anaerobic threshold is related to, but is lower than, the critical power, but does not explain exercise tolerance at this workrate.

PubMed

Okudan, N; Gökbel, H

2006-03-01

The aim of the present study was to investigate the relationships between critical power (CP), maximal aerobic power and the anaerobic threshold and whether exercise time to exhaustion and work at the CP can be used as an index in the determination of endurance. An incremental maximal cycle exercise test was performed on 30 untrained males aged 18-22 years. Lactate analysis was carried out on capillary blood samples at every 2 minutes. From gas exchange parameters and heart rate and lactate values, ventilatory anaerobic thresholds, heart rate deflection point and the onset of blood lactate accumulation were calculated. CP was determined with linear work-time method using 3 loads. The subjects exercised until they could no longer maintain a cadence above 24 rpm at their CP and exercise time to exhaustion was determined. CP was lower than the power output corresponding to VO2max, higher than the power outputs corresponding to anaerobic threshold. CP was correlated with VO2max and anaerobic threshold. Exercise time to exhaustion and work at CP were not correlated with VO2max and anaerobic threshold. Because of the correlations of the CP with VO2max and anaerobic threshold and no correlation of exercise time to exhaustion and work at the CP with these parameters, we conclude that exercise time to exhaustion and work at the CP cannot be used as an index in the determination of endurance.

Criticality in charge-asymmetric hard-sphere ionic fluids.

PubMed

Aqua, Jean-Noël; Banerjee, Shubho; Fisher, Michael E

2005-10-01

Phase separation and criticality are analyzed in z:1 charge-asymmetric ionic fluids of equisized hard spheres by generalizing the Debye-Hückel approach combined with ionic association, cluster solvation by charged ions, and hard-core interactions, following lines developed by Fisher and Levin for the 1:1 case (i.e., the restricted primitive model). Explicit analytical calculations for 2:1 and 3:1 systems account for ionic association into dimers, trimers, and tetramers and subsequent multipolar cluster solvation. The reduced critical temperatures, Tc* (normalized by z), decrease with charge asymmetry, while the critical densities increase rapidly with . The results compare favorably with simulations and represent a distinct improvement over all current theories such as the mean spherical approximation, symmetric Poisson-Boltzmann theory, etc. For z not equal to 1, the interphase Galvani (or absolute electrostatic) potential difference, Deltaphi(T), between coexisting liquid and vapor phases is calculated and found to vanish as absolute value (T-Tc) beta when T-->Tc-with, since our approximations are classical, beta = (1/2). Above Tc, the compressibility maxima and so-called k-inflection loci (which aid the fast and accurate determination of the critical parameters) are found to exhibit a strong z dependence.

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

Ngo, Sam; Guo, Zhefeng, E-mail: zhefeng@ucla.edu

Highlights: Black-Right-Pointing-Pointer A{beta} oligomers are neurotoxins and likely the causing agents for Alzheimer's disease. Black-Right-Pointing-Pointer A{beta}42 fusion protein form globular oligomers. Black-Right-Pointing-Pointer A{beta}42 fusion protein oligomers contain SDS-resistant tetramers and hexamers. Black-Right-Pointing-Pointer Cysteine substitutions at residues 31, 32, 34, 39-41 disrupt A{beta}42 oligomerization. -- Abstract: Deposition of amyloid fibrils consisting of amyloid {beta} (A{beta}) protein as senile plaques in the brain is a pathological hallmark of Alzheimer's disease. However, a growing body of evidence shows that soluble A{beta} oligomers correlate better with dementia than fibrils, suggesting that A{beta} oligomers may be the primary toxic species. The structure and oligomerization mechanismmore » of these A{beta} oligomers are crucial for developing effective therapeutics. Here we investigated the oligomerization of A{beta}42 in the context of a fusion protein containing GroES and ubiquitin fused to the N-terminus of A{beta} sequence. The presence of fusion protein partners, in combination with a denaturing buffer containing 8 M urea at pH 10, is unfavorable for A{beta}42 aggregation, thus allowing only the most stable structures to be observed. Transmission electron microscopy showed that A{beta}42 fusion protein formed globular oligomers, which bound weakly to thioflavin T and Congo red. SDS-PAGE shows that A{beta}42 fusion protein formed SDS-resistant hexamers and tetramers. In contrast, A{beta}40 fusion protein remained as monomers on SDS gel, suggesting that the oligomerization of A{beta}42 fusion protein is not due to the fusion protein partners. Cysteine scanning mutagenesis at 22 residue positions further revealed that single cysteine substitutions of the C-terminal hydrophobic residues (I31, I32, L34, V39, V40, and I41) led to disruption of hexamer and tetramer formation, suggesting that hydrophobic interactions between these residues are most critical for A{beta}42 oligomerization.« less

Critical oxygen levels and metabolic suppression in oceanic oxygen minimum zones.

PubMed

Seibel, Brad A

2011-01-15

The survival of oceanic organisms in oxygen minimum zones (OMZs) depends on their total oxygen demand and the capacities for oxygen extraction and transport, anaerobic ATP production and metabolic suppression. Anaerobic metabolism and metabolic suppression are required for daytime forays into the most extreme OMZs. Critical oxygen partial pressures are, within a range, evolved to match the minimum oxygen level to which a species is exposed. This fact demands that low oxygen habitats be defined by the biological response to low oxygen rather than by some arbitrary oxygen concentration. A broad comparative analysis of oxygen tolerance facilitates the identification of two oxygen thresholds that may prove useful for policy makers as OMZs expand due to climate change. Between these thresholds, specific physiological adaptations to low oxygen are required of virtually all species. The lower threshold represents a limit to evolved oxygen extraction capacity. Climate change that pushes oxygen concentrations below the lower threshold (~0.8 kPa) will certainly result in a transition from an ecosystem dominated by a diverse midwater fauna to one dominated by diel migrant biota that must return to surface waters at night. Animal physiology and, in particular, the response of animals to expanding hypoxia, is a critical, but understudied, component of biogeochemical cycles and oceanic ecology. Here, I discuss the definition of hypoxia and critical oxygen levels, review adaptations of animals to OMZs and discuss the capacity for, and prevalence of, metabolic suppression as a response to temporary residence in OMZs and the possible consequences of climate change on OMZ ecology.

Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths.

PubMed Central

Snyder, S W; Ladror, U S; Wade, W S; Wang, G T; Barrett, L W; Matayoshi, E D; Huffaker, H J; Krafft, G A; Holzman, T F

1994-01-01

One of the clinical manifestations of Alzheimer's disease is the deposition of the 39-43 residue amyloid-beta (A beta) peptide in aggregated fibrils in senile plaques. Characterization of the aggregation behavior of A beta is one of the critical issues in understanding the role of A beta in the disease process. Using solution hydrodynamics, A beta was observed to form three types of species in phosphate-buffered saline: insoluble aggregates with sedimentation coefficients of approximately 50,000 S and molecular masses of approximately 10(9) Da, "soluble aggregates" with sedimentation coefficients of approximately 30 S and masses of approximately 10(6) Da, and monomer. When starting from monomer, the aggregation kinetics of A beta 1-40 (A beta 40) and A beta 1-42 (A beta 42), alone and in combination, reveal large differences in the tendency of these peptides to aggregate as a function of pH and other solution conditions. At pH 4.1 and 7.0-7.4, aggregation is significantly slower than at pH 5 and 6. Under all conditions, aggregation of the longer A beta 42 was more rapid than A beta 40. Oxidation of Met-35 to the sulfoxide in A beta 40 enhances the aggregation rate over that of the nonoxidized peptide. Aggregation was found to be dependent upon temperature and to be strongly dependent on peptide concentration and ionic strength, indicating that aggregation is driven by a hydrophobic effect. When A beta 40 and A beta 42 are mixed together, A beta 40 retards the aggregation of A beta 42 in a concentration-dependent manner. Shorter fragments have a decreasing ability to interfere with A beta 42 aggregation. Conversely, the rate of aggregation of A beta 40 can be significantly enhanced by seeding slow aggregating solutions with preformed aggregates of A beta 42. Taken together, the inhibition of A beta 42 aggregation by A beta 40, the seeding of A beta 40 aggregation by A beta 42 aggregates, and the chemical oxidation of A beta 40 suggest that the relative abundance and rates of production of different-length A beta and its exposure to radical damage may be factors in the accumulation of A beta in plaques in vivo. Images FIGURE 6 PMID:7811936

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

Streltsov, Victor A.; Titmuss, Stephen J.; Epa, V. Chandana

Neurodegeneration observed in Alzheimer disease (AD) is believed to be related to the toxicity from reactive oxygen species (ROS) produced in the brain by the amyloid-{beta} (A{beta}) protein bound primarily to copper ions. The evidence for an oxidative stress role of A{beta}-Cu redox chemistry is still incomplete. Details of the copper binding site in A{beta} may be critical to the etiology of AD. Here we present the structure determined by combining x-ray absorption spectroscopy (XAS) and density functional theory analysis of A{beta} peptides complexed with Cu{sup 2+} in solution under a range of buffer conditions. Phosphate-buffered saline buffer salt (NaCl)more » concentration does not affect the high-affinity copper binding mode but alters the second coordination sphere. The XAS spectra for truncated and full-length A{beta}-Cu{sup 2+} peptides are similar. The novel distorted six-coordinated (3N3O) geometry around copper in the A{beta}-Cu{sup 2+} complexes include three histidines: glutamic, or/and aspartic acid, and axial water. The structure of the high-affinity Cu{sup 2+} binding site is consistent with the hypothesis that the redox activity of the metal ion bound to A{beta} can lead to the formation of dityrosine-linked dimers found in AD.« less

Transforming growth factor-beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin. I. Excisional wound model.

PubMed

Quaglino, D; Nanney, L B; Kennedy, R; Davidson, J M

1990-09-01

The effect of transforming growth factor-beta 1 (TGF-beta 1) on matrix gene expression has been investigated during the process of wound repair, where the formation of new connective tissue represents a critical step in restoring tissue integrity. Split-thickness excisional wounds in the pig were studied by in situ hybridization in order to obtain subjective findings on the activity and location of cells involved in matrix gene expression after the administration of recombinant TGF-beta 1. Data focus on the stimulatory role of this growth factor in granulation tissue formation, on the enhanced mRNA content of collagen types I and III, fibronectin, TGF-beta 1 itself, and on the reduction in stromelysin mRNA, suggesting that increased matrix formation measured after treatment with TGF-beta 1 is due to fibroplasia regulated by the abundance of mRNAs for several different structural, matrix proteins as well as inhibition of proteolytic phenomena elicited by metalloproteinases. These studies reveal elastin mRNA early in the repair process, and elastin mRNA expression is enhanced by administration of TGF-beta 1. Moreover, we show that TGF-beta 1 was auto-stimulating in wounds, accounting, at least in part, for the persistent effects of single doses of this multipotential cytokine.

The Global Spike: Conserved Dendritic Properties Enable Unique Ca2+ Spike Generation in Low-Threshold Spiking Neurons.

PubMed

Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

2015-11-25

Low-threshold Ca(2+) spikes (LTS) are an indispensible signaling mechanism for neurons in areas including the cortex, cerebellum, basal ganglia, and thalamus. They have critical physiological roles and have been strongly associated with disorders including epilepsy, Parkinson's disease, and schizophrenia. However, although dendritic T-type Ca(2+) channels have been implicated in LTS generation, because the properties of low-threshold spiking neuron dendrites are unknown, the precise mechanism has remained elusive. Here, combining data from fluorescence-targeted dendritic recordings and Ca(2+) imaging from low-threshold spiking cells in rat brain slices with computational modeling, the cellular mechanism responsible for LTS generation is established. Our data demonstrate that key somatodendritic electrical conduction properties are highly conserved between glutamatergic thalamocortical neurons and GABAergic thalamic reticular nucleus neurons and that these properties are critical for LTS generation. In particular, the efficiency of soma to dendrite voltage transfer is highly asymmetric in low-threshold spiking cells, and in the somatofugal direction, these neurons are particularly electrotonically compact. Our data demonstrate that LTS have remarkably similar amplitudes and occur synchronously throughout the dendritic tree. In fact, these Ca(2+) spikes cannot occur locally in any part of the cell, and hence we reveal that LTS are generated by a unique whole-cell mechanism that means they always occur as spatially global spikes. This all-or-none, global electrical and biochemical signaling mechanism clearly distinguishes LTS from other signals, including backpropagating action potentials and dendritic Ca(2+)/NMDA spikes, and has important consequences for dendritic function in low-threshold spiking neurons. Low-threshold Ca(2+) spikes (LTS) are critical for important physiological processes, including generation of sleep-related oscillations, and are implicated in disorders including epilepsy, Parkinson's disease, and schizophrenia. However, the mechanism underlying LTS generation in neurons, which is thought to involve dendritic T-type Ca(2+) channels, has remained elusive due to a lack of knowledge of the dendritic properties of low-threshold spiking cells. Combining dendritic recordings, two-photon Ca(2+) imaging, and computational modeling, this study reveals that dendritic properties are highly conserved between two prominent low-threshold spiking neurons and that these properties underpin a whole-cell somatodendritic spike generation mechanism that makes the LTS a unique global electrical and biochemical signal in neurons. Copyright © 2015 Connelly et al.

A study on the temperature dependence of the threshold switching characteristics of Ge2Sb2Te5

NASA Astrophysics Data System (ADS)

Lee, Suyoun; Jeong, Doo Seok; Jeong, Jeung-hyun; Zhe, Wu; Park, Young-Wook; Ahn, Hyung-Woo; Cheong, Byung-ki

2010-01-01

We investigated the temperature dependence of the threshold switching characteristics of a memory-type chalcogenide material, Ge2Sb2Te5. We found that the threshold voltage (Vth) decreased linearly with temperature, implying the existence of a critical conductivity of Ge2Sb2Te5 for its threshold switching. In addition, we investigated the effect of bias voltage and temperature on the delay time (tdel) of the threshold switching of Ge2Sb2Te5 and described the measured relationship by an analytic expression which we derived based on a physical model where thermally activated hopping is a dominant transport mechanism in the material.

Investigating Over Critical Thresholds of Forest Megafires Danger Conditions in Europe Utilising the ECMWF ERA-Interim Reanalysis

NASA Astrophysics Data System (ADS)

Petroliagkis, Thomas I.; Camia, Andrea; Liberta, Giorgio; Durrant, Tracy; Pappenberger, Florian; San-Miguel-Ayanz, Jesus

2014-05-01

The European Forest Fire Information System (EFFIS) has been established by the Joint Research Centre (JRC) and the Directorate General for Environment (DG ENV) of the European Commission (EC) to support the services in charge of the protection of forests against fires in the EU and neighbour countries, and also to provide the EC services and the European Parliament with information on forest fires in Europe. Within its applications, EFFIS provides current and forecast meteorological fire danger maps up to 6 days. Weather plays a key role in affecting wildfire occurrence and behaviour. Meteorological parameters can be used to derive meteorological fire weather indices that provide estimations of fire danger level at a given time over a specified area of interest. In this work, we investigate the suitability of critical thresholds of fire danger to provide an early warning for megafires (fires > 500 ha) over Europe. Past trends of fire danger are analysed computing daily fire danger from weather data taken from re-analysis fields for a period of 31 years (1980 to 2010). Re-analysis global data sets coming from the construction of high-quality climate records, which combine past observations collected from many different observing and measuring platforms, are capable of describing how Fire Danger Indices have evolved over time at a global scale. The latest and most updated ERA-Interim dataset of the European Centre for Medium-Range Weather Forecast (ECMWF) was used to extract meteorological variables needed to compute daily values of the Canadian Fire Weather Index (CFWI) over Europe, with a horizontal resolution of about 75x75 km. Daily time series of CFWI were constructed and analysed over a total of 1,071 European NUTS3 centroids, resulting in a set of percentiles and critical thresholds. Such percentiles could be used as thresholds to help fire services establish a measure of the significance of CFWI outputs as they relate to levels of fire potential, fuel conditions and fire danger. Median percentile values of fire days accumulated over the 31-year period were compared to median values of all days from that period. As expected, the CWFI time series exhibit different values on fire days than on all days. In addition, a percentile analysis was performed in order to determine the behaviour of index values corresponding to fire events falling into the megafire category. This analysis resulted in a set of critical thresholds based on percentiles. By utilising such thresholds, an initial framework of an early warning system has being established. By lowering the value of any of these thresholds, the number of hits could be increased until all extremes were captured (resulting in zero misses). However, in doing so, the number of false alarms tends to increase significantly. Consequently, an optimal trade-off between hits and false alarms has to be established when setting different (critical) CFWI thresholds.

Using Smartphones to Monitor Bipolar Disorder Symptoms: A Pilot Study

PubMed Central

Kindermann, Sally; Maier, Andreas; Kerl, Christopher; Moock, Jörn; Barbian, Guido; Rössler, Wulf

2016-01-01

Background Relapse prevention in bipolar disorder can be improved by monitoring symptoms in patients' daily life. Smartphone apps are easy-to-use, low-cost tools that can be used to assess this information. To date, few studies have examined the usefulness of smartphone data for monitoring symptoms in bipolar disorder. Objective We present results from a pilot test of a smartphone-based monitoring system, Social Information Monitoring for Patients with Bipolar Affective Disorder (SIMBA), that tracked daily mood, physical activity, and social communication in 13 patients. The objective of this study was to investigate whether smartphone measurements predicted clinical symptoms levels and clinical symptom change. The hypotheses that smartphone measurements are (1) negatively related to clinical depressive symptoms and (2) positively related to clinical manic symptoms were tested. Methods Clinical rating scales were administered to assess clinical depressive and manic symptoms. Patients used a smartphone with the monitoring app for up to 12 months. Random-coefficient multilevel models were computed to analyze the relationship between smartphone data and externally rated manic and depressive symptoms. Overall clinical symptom levels and clinical symptom changes were predicted by separating between-patient and within-patient effects. Using established clinical thresholds from the literature, marginal effect plots displayed clinical relevance of smartphone data. Results Overall symptom levels and change in clinical symptoms were related to smartphone measures. Higher overall levels of clinical depressive symptoms were predicted by lower self-reported mood measured by the smartphone (beta=-.56, P<.001). An increase in clinical depressive symptoms was predicted by a decline in social communication (ie, outgoing text messages: beta=-.28, P<.001) and a decline in physical activity as measured by the smartphone (ie, cell tower movements: beta=-.11, P=.03). Higher overall levels of clinical manic symptoms were predicted by lower physical activity on the smartphone (ie, distance travelled: beta=-.37, P<.001), and higher social communication (beta=.48, P=.03). An increase in clinical manic symptoms was predicted by a decrease in physical activity on the smartphone (beta=-.17, P<.001). Conclusions Clinical symptoms were related to some objective and subjective smartphone measurements, but not all smartphone measures predicted the occurrence of bipolar symptoms above clinical thresholds. Thus, smartphones have the potential to monitor bipolar disorder symptoms in patients’ daily life. Further validation of monitoring tools in a larger sample is needed. Conclusions are limited by the low prevalence of manic and depressive symptoms in the study sample. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 05663421; http://www.controlled-trials.com/ISRCTN05663421 (Archived by WebCite at http://www.webcitation.org/6d9wsibJB) PMID:26740354

Higgs boson gluon-fusion production beyond threshold in N 3LO QCD

DOE PAGES

Anastasiou, Charalampos; Duhr, Claude; Dulat, Falko; ...

2015-03-18

In this study, we compute the gluon fusion Higgs boson cross-section at N 3LO through the second term in the threshold expansion. This calculation constitutes a major milestone towards the full N 3LO cross section. Our result has the best formal accuracy in the threshold expansion currently available, and includes contributions from collinear regions besides subleading corrections from soft and hard regions, as well as certain logarithmically enhanced contributions for general kinematics. We use our results to perform a critical appraisal of the validity of the threshold approximation at N 3LO in perturbative QCD.

The hepta-beta-glucoside elicitor-binding proteins from legumes represent a putative receptor family.

PubMed

Mithöfer, A; Fliegmann, J; Neuhaus-Url, G; Schwarz, H; Ebel, J

2000-08-01

The ability of legumes to recognize and respond to beta-glucan elicitors by synthesizing phytoalexins is consistent with the existence of a membrane-bound beta-glucan-binding site. Related proteins of approximately 75 kDa and the corresponding mRNAs were detected in various species of legumes which respond to beta-glucans. The cDNAs for the beta-glucan-binding proteins of bean and soybean were cloned. The deduced 75-kDa proteins are predominantly hydrophilic and constitute a unique class of glucan-binding proteins with no currently recognizable functional domains. Heterologous expression of the soybean beta-glucan-binding protein in tomato cells resulted in the generation of a high-affinity binding site for the elicitor-active hepta-beta-glucoside conjugate (Kd = 4.5 nM). Ligand competition experiments with the recombinant binding sites demonstrated similar ligand specificities when compared with soybean. In both soybean and transgenic tomato, membrane-bound, active forms of the glucan-binding proteins coexist with immunologically detectable, soluble but inactive forms of the proteins. Reconstitution of a soluble protein fraction into lipid vesicles regained beta-glucoside-binding activity but with lower affinity (Kd = 130 nM). We conclude that the beta-glucan elicitor receptors of legumes are composed of the 75 kDa glucan-binding proteins as the critical components for ligand-recognition, and of an as yet unknown membrane anchor constituting the plasma membrane-associated receptor complex.

Structural and biological mimicry of protein surface recognition by [alpha/beta]-peptide foldamers

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

Horne, W. Seth; Johnson, Lisa M.; Ketas, Thomas J.

Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining {alpha}- and {beta}-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that {alpha}/{beta}-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic {alpha}/{beta}-peptides effectively block HIV-cell fusion via a mechanism comparablemore » to that of gp41-derived {alpha}-peptides. An optimized {alpha}/{beta}-peptide is far less susceptible to proteolytic degradation than is an analogous {alpha}-peptide. Our findings show how a two-stage design approach, in which sequence-based {alpha} {yields} {beta} replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.« less

Use of Biotechnological Devices in the Quantification of Psychophysiological Workload of Professional Chess Players.

PubMed

Fuentes, Juan P; Villafaina, Santos; Collado-Mateo, Daniel; de la Vega, Ricardo; Gusi, Narcis; Clemente-Suárez, Vicente Javier

2018-01-19

Psychophysiological requirements of chess players are poorly understood, and periodization of training is often made without any empirical basis. For this reason, the aim of the present study was to investigate the psychophysiological response and quantify the player internal load during, and after playing a chess game. The participant was an elite 33 year-old male chess player ranked among the 300 best chess players in the world. Thus, cortical arousal by critical flicker fusion threshold, electroencephalogram by the theta Fz/alpha Pz ratio and autonomic modulation by heart rate variability were analyzed. Data revealed that cortical arousal by critical flicker fusion threshold and theta Fz/alpha Pz ratio increased and heart rate variability decreased during chess game. All these changes indicated that internal load increased during the chess game. In addition, pre-activation was detected in pre-game measure, suggesting that the prefrontal cortex might be preparatory activated. For these reasons, electroencephalogram, critical flicker fusion threshold and heart rate variability analysis may be highly applicable tools to control and monitor workload in chess player.

A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia.

PubMed

Lemper, Marie; De Groef, Sofie; Stangé, Geert; Baeyens, Luc; Heimberg, Harry

2016-09-01

When the beta cell mass or function declines beyond a critical point, hyperglycaemia arises. Little is known about the potential pathways involved in beta cell rescue. As two cytokines, epidermal growth factor (EGF) and ciliary neurotrophic factor (CNTF), restored a functional beta cell mass in mice with long-term hyperglycaemia by reprogramming acinar cells that transiently expressed neurogenin 3 (NGN3), the current study assesses the effect of these cytokines on the functional beta cell mass after an acute chemical toxic insult. Glycaemia and insulin levels, pro-endocrine gene expression and beta cell origin, as well as the role of signal transducer and activator of transcription 3 (STAT3) signalling, were assessed in EGF+CNTF-treated mice following acute hyperglycaemia. The mice were hyperglycaemic 1 day following i.v. injection of the beta cell toxin alloxan, when the two cytokines were applied. One week later, 68.6 ± 4.6% of the mice had responded to the cytokine treatment and increased their insulin(+) cell number to 30% that of normoglycaemic control mice, resulting in restoration of euglycaemia. Although insulin(-) NGN3(+) cells appeared following acute EGF+CNTF treatment, genetic lineage tracing showed that the majority of the insulin(+) cells originated from pre-existing beta cells. Beta cell rescue by EGF+CNTF depends on glycaemia rather than on STAT3-induced NGN3 expression in acinar cells. In adult mice, EGF+CNTF allows the rescue of beta cells in distress when treatment is given shortly after the diabetogenic insult. The rescued beta cells restore a functional beta cell mass able to control normal blood glucose levels. These findings may provide new insights into compensatory pathways activated early after beta cell loss.

Isomorphic Properties of Atoms, Molecules, Water, DNA, Crystals, Earth, SolarSystem and Galaxies

NASA Astrophysics Data System (ADS)

Gareev, F. A.; Gareeva, G. F.; Zhidkova, I. E.

2009-03-01

We discuss the cooperative resonance synchronization enhancement mechanisms of Low Energy Nuclear Reactions (LENR). Some of the low energy external fields can be used as triggers for starting and enhancing exothermic LENR. Any external field shortening distances between protons in nuclei and electrons in atoms should enhance beta-decay (capture) or double-beta decay (capture). We have proposed a new mechanism of LENR: cooperative resonance synchronization processes in the whole system nuclei+atoms+condensed matter+gaseuos+plasma medium, which we suggest can occur at a smaller threshold than the corresponding ones on free constituents. The cooperative processes can be induced and enhanced by low energy external fields. The excess heat is the emission of internal energy, and transmutations at LENR are the result of redistribution inner energy of the whole system.

Accuracy of topographic index models at identifying ephemeral gully trajectories on agricultural fields

NASA Astrophysics Data System (ADS)

Sheshukov, Aleksey Y.; Sekaluvu, Lawrence; Hutchinson, Stacy L.

2018-04-01

Topographic index (TI) models have been widely used to predict trajectories and initiation points of ephemeral gullies (EGs) in agricultural landscapes. Prediction of EGs strongly relies on the selected value of critical TI threshold, and the accuracy depends on topographic features, agricultural management, and datasets of observed EGs. This study statistically evaluated the predictions by TI models in two paired watersheds in Central Kansas that had different levels of structural disturbances due to implemented conservation practices. Four TI models with sole dependency on topographic factors of slope, contributing area, and planform curvature were used in this study. The observed EGs were obtained by field reconnaissance and through the process of hydrological reconditioning of digital elevation models (DEMs). The Kernel Density Estimation analysis was used to evaluate TI distribution within a 10-m buffer of the observed EG trajectories. The EG occurrence within catchments was analyzed using kappa statistics of the error matrix approach, while the lengths of predicted EGs were compared with the observed dataset using the Nash-Sutcliffe Efficiency (NSE) statistics. The TI frequency analysis produced bi-modal distribution of topographic indexes with the pixels within the EG trajectory having a higher peak. The graphs of kappa and NSE versus critical TI threshold showed similar profile for all four TI models and both watersheds with the maximum value representing the best comparison with the observed data. The Compound Topographic Index (CTI) model presented the overall best accuracy with NSE of 0.55 and kappa of 0.32. The statistics for the disturbed watershed showed higher best critical TI threshold values than for the undisturbed watershed. Structural conservation practices implemented in the disturbed watershed reduced ephemeral channels in headwater catchments, thus producing less variability in catchments with EGs. The variation in critical thresholds for all TI models suggested that TI models tend to predict EG occurrence and length over a range of thresholds rather than find a single best value.

Potts-model critical manifolds revisited

DOE PAGES

Scullard, Christian R.; Jacobsen, Jesper Lykke

2016-02-11

We compute the critical polynomials for the q-state Potts model on all Archimedean lattices, using a parallel implementation of the algorithm of Ref. [1] that gives us access to larger sizes than previously possible. The exact polynomials are computed for bases of size 6 6 unit cells, and the root in the temperature variable v = e K-1 is determined numerically at q = 1 for bases of size 8 8. This leads to improved results for bond percolation thresholds, and for the Potts-model critical manifolds in the real (q; v) plane. In the two most favourable cases, we findmore » now the kagome-lattice threshold to eleven digits and that of the (3; 12 2) lattice to thirteen. Our critical manifolds reveal many interesting features in the antiferromagnetic region of the Potts model, and determine accurately the extent of the Berker-Kadano phase for the lattices studied.« less

Comprehensive analysis of all triple helical repeats in beta-spectrins reveals patterns of selective evolutionary conservation.

PubMed

Baines, Anthony J

2003-01-01

The spectrin superfamily (spectrin, alpha-actinin, utrophin and dystrophin) has in common a triple helical repeating unit of ~106 amino acid residues. In spectrin, alpha and beta chains contain multiple copies of this repeat. beta-spectrin chains contain the majority of binding activities in spectrin and are essential for animal life. Canonical beta-spectrins have 17 repeats; beta-heavy spectrins have 30. Here, the repeats of five human beta-spectrins, plus beta-spectrins from several other vertebrates and invertebrates, have been analysed. Repeats 1, 2, 14 and 17 in canonical beta are highly conserved between invertebrates and vertebrates, and repeat 8 in some isoforms. This is consistent with conservation of critical functions, since repeats 1, 2 and 17 bind alpha-spectrin. Repeats 1 of beta-spectrins are not always detected by SMART or Pfam tools. A profile hidden Markov model of beta-spectrin repeat 1 detects alpha-actinins, but not utrophin or dystrophin. Novel examples of repeat 1 were detected in the spectraplakins MACF1, BPAG1 and plectin close to the actin-binding domain. Ankyrin binds to the C-terminal portion of repeat 14; the high conservation of this entire repeat may point to additional, undiscovered ligand-binding activities. This analysis indicates that the basic triple helical repeat pattern was adapted early in the evolution of the spectrin superfamily to encompass essential binding activities, which characterise individual repeats in proteins extant today.

Peroxisome proliferator-activated receptor {gamma} is expressed in hippocampal neurons and its activation prevents {beta}-amyloid neurodegeneration: role of Wnt signaling

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

Inestrosa, Nibaldo C.; Godoy, Juan A.; MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago

2005-03-10

The molecular pathogenesis of Alzheimer's disease (AD) involves the participation of the amyloid-{beta}-peptide (A{beta}), which plays a critical role in the neurodegeneration that triggers the disease. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which are members of the nuclear receptor family. We report here that (1) PPAR{gamma} is present in rat hippocampal neurons in culture. (2) Activation of PPAR{gamma} by troglitazone and rosiglitazone protects rat hippocampal neurons against A{beta}-induced neurodegeneration, as shown by the 3-[4,5 -2yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay, immunofluorescence using an anti-heavy neurofilament antibody, and quantitative electron microscopy. (3) Hippocampal neurons treated with several PPAR{gamma} agonists, includingmore » troglitazone, rosiglitazone, and ciglitazone, prevent the excitotoxic A{beta}-induced rise in bulk-free Ca{sup 2+}. (4) PPAR{gamma} activation results in the modulation of Wnt signaling components, including the inhibition of glycogen synthase kinase-3{beta} (GSK-3{beta}) and an increase of the cytoplasmic and nuclear {beta}-catenin levels. We conclude that the activation of PPAR{gamma} prevents A{beta}-induced neurodegeneration by a mechanism that may involve a cross talk between neuronal PPAR{gamma} and the Wnt signaling pathway. More important, the fact that the activation of PPAR{gamma} attenuated A{beta}-dependent neurodegeneration opens the possibility to fight AD from a new therapeutic perspective.« less

Atherosclerosis and Liver Function Tests in Coronary Angiography Patients.

PubMed

Doganer, Y C; Rohrer, J E; Aydogan, U; Agerter, D C; Cayci, T; Barcin, C

2015-09-01

Elevated aminotransferase levels indicating liver function, even in the normal range, have attracted great concern as potential novel markers of cardiovascular risk assessment. We hypothesized the possibility that liver function test variations in the normal range might be meaningfully associated to coronary artery disease (CAD). Eighty-eight patients were randomly selected from those who underwent coronary angiography from June 2010 to June 2011 after applying to the outpatient cardiology clinic in Gulhane Military Medical Academy. According to the results of angiographies, patients were classified into three groups as normal, non-critical (< 50% involvement in coronaries), and critical (≥ 50% involvement in coronaries). In addition to angiographic intervention, measurements of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, albumin and the other serum parameters were performed in all patients. The patient groups of CAD were balanced (28 critical cases, 30 non-critical cases and 30 normal cases). Mean age was 51.93 ± 9.3 (range 32-65) years and 19.3 per cent (n = 17) were females. Multiple linear regression analysis of all three liver function tests explained a significant portion of the variance, but adjusted r-squares were small (AST = 0.174, ALT = 0.242, albumin = 0.124). Albumin was significantly higher for patients with critical CAD than for patients with no CAD (beta = 3.205, p = 0.002). Non-critical CAD was not significantly different from no CAD for any of the dependent variables. Mean AST was significantly higher for patients taking aspirin (beta = 0.218, p = 0.049), as was mean ALT (beta = 0.264, p = 0.015). Alanine aminotransferase and AST may not be associated with angiographically determined coronary atherosclerosis. Albumin may be more sensitive to demonstrate the burden of atherosclerosis. These results indicate that the association between the liver function tests and coronary atherosclerosis may be more complex than generally appreciated.

Low Oxygen Delivery as a Predictor of Acute Kidney Injury during Cardiopulmonary Bypass.

PubMed

Newland, Richard F; Baker, Robert A

2017-12-01

Low indexed oxygen delivery (DO 2 i) during cardiopulmonary bypass (CPB) has been associated with an increase in the likelihood of acute kidney injury (AKI), with critical thresholds for oxygen delivery reported to be 260-270 mL/min/m 2 . This study aims to explore whether a relationship exists for oxygen delivery during CPB, in which the integral of amount and time below a critical threshold, is associated with the incidence of postoperative AKI. The area under the curve (AUC) with DO 2 i during CPB above or below 270 mL/min/m 2 was calculated as a metric of oxygen delivery in 210 patients undergoing CPB. To determine the influence of low oxygen delivery on AKI, a multivariate logistic regression model was developed including AUC < 0, Euroscore II to provide preoperative risk factor adjustment, and incidence of red blood cell transfusion to adjust for the influence of transfusion. Having an AUC < 0 for an oxygen delivery threshold of 270 mL/min/m 2 during CPB was an independent predictor of AKI, after adjustment for Euroscore II and transfusion [OR 2.74, CI {1.01-7.41}, p = .047]. These results support that a relationship exists for oxygen delivery during CPB, in which the integral of amount and time below a critical threshold is associated with the incidence of postoperative AKI.

Nonsinusoidal Beta Oscillations Reflect Cortical Pathophysiology in Parkinson's Disease.

PubMed

Cole, Scott R; van der Meij, Roemer; Peterson, Erik J; de Hemptinne, Coralie; Starr, Philip A; Voytek, Bradley

2017-05-03

Oscillations in neural activity play a critical role in neural computation and communication. There is intriguing new evidence that the nonsinusoidal features of the oscillatory waveforms may inform underlying physiological and pathophysiological characteristics. Time-domain waveform analysis approaches stand in contrast to traditional Fourier-based methods, which alter or destroy subtle waveform features. Recently, it has been shown that the waveform features of oscillatory beta (13-30 Hz) events, a prominent motor cortical oscillation, may reflect near-synchronous excitatory synaptic inputs onto cortical pyramidal neurons. Here we analyze data from invasive human primary motor cortex (M1) recordings from patients with Parkinson's disease (PD) implanted with a deep brain stimulator (DBS) to test the hypothesis that the beta waveform becomes less sharp with DBS, suggesting that M1 input synchrony may be decreased. We find that, in PD, M1 beta oscillations have sharp, asymmetric, nonsinusoidal features, specifically asymmetries in the ratio between the sharpness of the beta peaks compared with the troughs. This waveform feature is nearly perfectly correlated with beta-high gamma phase-amplitude coupling ( r = 0.94), a neural index previously shown to track PD-related motor deficit. Our results suggest that the pathophysiological beta generator is altered by DBS, smoothing out the beta waveform. This has implications not only for the interpretation of the physiological mechanism by which DBS reduces PD-related motor symptoms, but more broadly for our analytic toolkit in general. That is, the often-overlooked time-domain features of oscillatory waveforms may carry critical physiological information about neural processes and dynamics. SIGNIFICANCE STATEMENT To better understand the neural basis of cognition and disease, we need to understand how groups of neurons interact to communicate with one another. For example, there is evidence that parkinsonian bradykinesia and rigidity may arise from an oversynchronization of afferents to the motor cortex, and that these symptoms are treatable using deep brain stimulation. Here we show that the waveform shape of beta (13-30 Hz) oscillations, which may reflect input synchrony onto the cortex, is altered by deep brain stimulation. This suggests that mechanistic inferences regarding physiological and pathophysiological neural communication may be made from the temporal dynamics of oscillatory waveform shape. Copyright © 2017 the authors 0270-6474/17/374830-11$15.00/0.

Effects of folic acid deficiency in pregnant Wistar rats on the activities of D5-3 beta hydroxysteroid dehydrogenase and glucose-6 phosphate dehydrogenase in the ovaries of their litters.

PubMed

Uche-Nwachi, E O; Caxton-Martins, A E

1997-06-01

Histochemical studies of the activities of glucose-6-phosphate dehydrogenase (G-6-PD) and D5-3 beta-hydroxysteroid dehydrogenase (D5-3 beta-HSD) in the ovaries of 40 day old litters of Wistar rats whose mothers were folic acid deficient from the 13th day of gestation showed very weak or no enzyme activity. Biochemical estimations of these enzymes showed that the specific activity of 3 beta-HSD in the experimental animal was 20% that of control while that of G-6-PD in the experimental animals was 14% that of control. This implies that folic acid deficiency instituted at a critical period in gestation in Wistar rats adversely affects steroidogenesis in the ovaries of their litters.

Technology Thresholds for Microgravity: Status and Prospects

NASA Technical Reports Server (NTRS)

Noever, D. A.

1996-01-01

The technological and economic thresholds for microgravity space research are estimated in materials science and biotechnology. In the 1990s, the improvement of materials processing has been identified as a national scientific priority, particularly for stimulating entrepreneurship. The substantial US investment at stake in these critical technologies includes six broad categories: aerospace, transportation, health care, information, energy, and the environment. Microgravity space research addresses key technologies in each area. The viability of selected space-related industries is critically evaluated and a market share philosophy is developed, namely that incremental improvements in a large markets efficiency is a tangible reward from space-based research.

Regulation of insulin exocytosis by calcium-dependent protein kinase C in beta cells.

PubMed

Trexler, Adam J; Taraska, Justin W

2017-11-01

The control of insulin release from pancreatic beta cells helps ensure proper blood glucose level, which is critical for human health. Protein kinase C has been shown to be one key control mechanism for this process. After glucose stimulation, calcium influx into beta cells triggers exocytosis of insulin-containing dense-core granules and activates protein kinase C via calcium-dependent phospholipase C-mediated generation of diacylglycerol. Activated protein kinase C potentiates insulin release by enhancing the calcium sensitivity of exocytosis, likely by affecting two main pathways that could be linked: (1) the reorganization of the cortical actin network, and (2) the direct phosphorylation of critical exocytotic proteins such as munc18, SNAP25, and synaptotagmin. Here, we review what is currently known about the molecular mechanisms of protein kinase C action on each of these pathways and how these effects relate to the control of insulin release by exocytosis. We identify remaining challenges in the field and suggest how these challenges might be addressed to advance our understanding of the regulation of insulin release in health and disease. Published by Elsevier Ltd.

Top-Down Beta Rhythms Support Selective Attention via Interlaminar Interaction: A Model

PubMed Central

Lee, Jung H.; Whittington, Miles A.; Kopell, Nancy J.

2013-01-01

Cortical rhythms have been thought to play crucial roles in our cognitive abilities. Rhythmic activity in the beta frequency band, around 20 Hz, has been reported in recent studies that focused on neural correlates of attention, indicating that top-down beta rhythms, generated in higher cognitive areas and delivered to earlier sensory areas, can support attentional gain modulation. To elucidate functional roles of beta rhythms and underlying mechanisms, we built a computational model of sensory cortical areas. Our simulation results show that top-down beta rhythms can activate ascending synaptic projections from L5 to L4 and L2/3, responsible for biased competition in superficial layers. In the simulation, slow-inhibitory interneurons are shown to resonate to the 20 Hz input and modulate the activity in superficial layers in an attention-related manner. The predicted critical roles of these cells in attentional gain provide a potential mechanism by which cholinergic drive can support selective attention. PMID:23950699

Ecological thresholds: The key to successful enviromental management or an important concept with no practical application?

USGS Publications Warehouse

Groffman, P.M.; Baron, Jill S.; Blett, T.; Gold, A.J.; Goodman, I.; Gunderson, L.H.; Levinson, B.M.; Palmer, Margaret A.; Paerl, H.W.; Peterson, G.D.; Poff, N.L.; Rejeski, D.W.; Reynolds, J.F.; Turner, M.G.; Weathers, K.C.; Wiens, J.

2006-01-01

An ecological threshold is the point at which there is an abrupt change in an ecosystem quality, property or phenomenon, or where small changes in an environmental driver produce large responses in the ecosystem. Analysis of thresholds is complicated by nonlinear dynamics and by multiple factor controls that operate at diverse spatial and temporal scales. These complexities have challenged the use and utility of threshold concepts in environmental management despite great concern about preventing dramatic state changes in valued ecosystems, the need for determining critical pollutant loads and the ubiquity of other threshold-based environmental problems. In this paper we define the scope of the thresholds concept in ecological science and discuss methods for identifying and investigating thresholds using a variety of examples from terrestrial and aquatic environments, at ecosystem, landscape and regional scales. We end with a discussion of key research needs in this area.

Phosphorylation of PPP(S/T)P motif of the free LRP6 intracellular domain is not required to activate the Wnt/beta-catenin pathway and attenuate GSK3beta activity.

PubMed

Beagle, Brandon; Mi, Kaihong; Johnson, Gail V W

2009-11-01

The canonical Wnt/beta-catenin signaling pathway plays a critical role in numerous physiological and pathological processes. LRP6 is an essential co-receptor for Wnt/beta-catenin signaling; as transduction of the Wnt signal is strongly dependent upon GSK3beta-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane-anchored LRP6 intracellular domain. Previously, we showed that the free LRP6 intracellular domain (LRP6-ICD) can activate the Wnt/beta-catenin pathway in a beta-catenin and TCF/LEF-1 dependent manner, as well as interact with and attenuate GSK3beta activity. However, it is unknown if the ability of LRP6-ICD to attenuate GSK3beta activity and modulate activation of the Wnt/beta-catenin pathway requires phosphorylation of the LRP6-ICD PPP(S/T)P motifs, in a manner similar to the membrane-anchored LRP6 intracellular domain. Here we provide evidence that the LRP6-ICD does not have to be phosphorylated at its PPP(S/T)P motif by GSK3beta to stabilize endogenous cytosolic beta-catenin resulting in activation of TCF/LEF-1 and the Wnt/beta-catenin pathway. LRP6-ICD and a mutant in which all 5 PPP(S/T)P motifs were changed to PPP(A)P motifs equivalently interacted with and attenuated GSK3beta activity in vitro, and both constructs inhibited the in situ GSK3beta-mediated phosphorylation of beta-catenin and tau to the same extent. These data indicate that the LRP6-ICD attenuates GSK3beta activity similar to other GSK3beta binding proteins, and is not a result of it being a GSK3beta substrate. Our findings suggest the functional and regulatory mechanisms governing the free LRP6-ICD may be distinct from membrane-anchored LRP6, and that release of the LRP6-ICD may provide a complimentary signaling cascade capable of modulating Wnt-dependent gene expression. (c) 2009 Wiley-Liss, Inc.

The temporal dimension of regime shifts: How long can ecosystems operate beyond critical thresholds before transitions become irreversible?

USDA-ARS?s Scientific Manuscript database

Background/Question/Methods: Ecosystem thresholds are often identified by observing or inducing slow changes in different driver variables and investigating changes in the asymptotic state of the system, such as the response of lakes to nutrient loading or biome responses to climate change. Yet ma...

Refinement of determination of critical thresholds of stress-strain behaviour by using AE data: potential for evaluation of durability of natural stone

NASA Astrophysics Data System (ADS)

Prikryl, Richard; Lokajíček, Tomáš

2017-04-01

According to previous studies, evaluation of stress-strain behaviour (in uniaxial compression) of various rocks appears to be effective tool allowing for prediction of resistance of natural stone to some physical weathering processes. Precise determination of critical thresholds, specifically of 'crack initiation' and 'crack damage' is fundamental issue in this approach. In contrast to 'crack damage stress/strain threshold', which can be easily read from deflection point on volumetric curve, detection of 'crack initiation' is much more difficult. Besides previously proposed mathematical processing of axial stress-strain curve, recording of acoustic emission (AE) data and their processing provide direct measure of various stress/strain thresholds, specifically of 'crack initiation'. This specific parameter is required during successive computation of energetic parameters (mechanical work), that can be stored by a material without formation of new defects (microcracks) due to acting stress. Based on our experimental data, this mechanical work seems to be proportional to the resistance of a material to formation of mode I (tensile) cracks that are responsible for destruction of subsurface below exposed faces of natural stone.

Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines.

PubMed

Shan, Hongli; Zhang, Yong; Lu, Yanjie; Zhang, Ying; Pan, Zhenwei; Cai, Benzhi; Wang, Ning; Li, Xuelian; Feng, Tieming; Hong, Yuan; Yang, Baofeng

2009-08-01

The present study was designed to decipher molecular mechanisms underlying nicotine's promoting atrial fibrillation (AF) by inducing atrial structural remodelling. The canine model of AF was successfully established by nicotine administration and rapid pacing. The atrial fibroblasts isolated from healthy dogs were treated with nicotine. The role of microRNAs (miRNAs) on the expression and regulation of transforming growth factor-beta1 (TGF-beta1), TGF-beta receptor type II (TGF-betaRII), and collagen production was evaluated in vivo and in vitro. Administration of nicotine for 30 days increased AF vulnerability by approximately eight- to 15-fold in dogs. Nicotine stimulated remarkable collagen production and atrial fibrosis both in vitro in cultured canine atrial fibroblasts and in vivo in atrial tissues. Nicotine produced significant upregulation of expression of TGF-beta1 and TGF-betaRII at the protein level, and a 60-70% decrease in the levels of miRNAs miR-133 and miR-590. This downregulation of miR-133 and miR-590 partly accounts for the upregulation of TGF-beta1 and TGF-betaRII, because our data established TGF-beta1 and TGF-betaRII as targets for miR-133 and miR-590 repression. Transfection of miR-133 or miR-590 into cultured atrial fibroblasts decreased TGF-beta1 and TGF-betaRII levels and collagen content. These effects were abolished by the antisense oligonucleotides against miR-133 or miR-590. The effects of nicotine were prevented by an alpha7 nicotinic acetylcholine receptor antagonist. We conclude that the profibrotic response to nicotine in canine atrium is critically dependent upon downregulation of miR-133 and miR-590.

Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis?

PubMed Central

Chambers, H F; Moreau, D; Yajko, D; Miick, C; Wagner, C; Hackbarth, C; Kocagöz, S; Rosenberg, E; Hadley, W K; Nikaido, H

1995-01-01

An increase in the number of tuberculosis cases caused by multiple-drug-resistant strains of Mycobacterium tuberculosis has stimulated search for new antituberculous agents. Beta-lactam antibiotics, traditionally regarded as ineffective against tuberculosis, merit consideration. Four major penicillin-binding proteins (PBPs) with approximate molecular sizes of 94, 82, 52, and 37 kDa were detected by fluorography of [3H]penicillin-radiolabeled membrane proteins prepared from M. tuberculosis H37Ra. The presence of membrane-associated beta-lactamase precluded the use of membranes for assaying the binding affinities of beta-lactam antibiotics. Therefore, ampicillin affinity chromatography was used to purify these four PBPs from crude membranes in order to assay the binding affinities of beta-lactam antibiotics. Ampicillin, amoxicillin, and imipenem, beta-lactam antibiotics previously reported to be active in vitro against M. tuberculosis, bound to M. tuberculosis PBPs at therapeutically achievable concentrations. Binding of the 94-, 82-, and 52-kDa PBPs, but not the 37-kDa PBP, was associated with antibacterial activity, suggesting that these PBPs are the critical targets. Studies of mycobacterial cell wall permeability, which was assayed with a panel of reference cephalosporins and penicillins with different charge positivities, indicated that the rate of penetration of beta-lactam antibiotics to the target PBPs could not account for resistance. Resistance could be reversed with the beta-lactamase inhibitors clavulanate or sulbactam or could be circumvented by the use of a beta-lactamase-stable drug, imipenem, indicating that mycobacterial beta-lactamase, probably in conjunction with slow penetration, is a major determinant of M. tuberculosis resistance to beta-lactam antibiotics. These findings confirm in vitro data that M. tuberculosis is susceptible to some beta-lactam antibiotics. Further evaluation of these drugs for the treatment of tuberculosis in animal models and in clinical trials is warranted. PMID:8592990

Threshold of coexistence and critical behavior of a predator-prey stochastic model in a fractal landscape

NASA Astrophysics Data System (ADS)

Argolo, C.; Barros, P.; Tomé, T.; Arashiro, E.; Gleria, Iram; Lyra, M. L.

2016-08-01

We investigate a stochastic lattice model describing a predator-prey system in a fractal scale-free landscape, mimicked by the fractal Sierpinski carpet. We determine the threshold of species coexistence, that is, the critical phase boundary related to the transition between an active state, where both species coexist and an absorbing state where one of the species is extinct. We show that the predators must live longer in order to persist in a fractal habitat. We further performed a finite-size scaling analysis in the vicinity of the absorbing-state phase transition to compute a set of stationary and dynamical critical exponents. Our results indicate that the transition belongs to the directed percolation universality class exhibited by the usual contact process model on the same fractal landscape.

Non-equilibrium relaxation in a stochastic lattice Lotka-Volterra model

NASA Astrophysics Data System (ADS)

Chen, Sheng; Täuber, Uwe C.

2016-04-01

We employ Monte Carlo simulations to study a stochastic Lotka-Volterra model on a two-dimensional square lattice with periodic boundary conditions. If the (local) prey carrying capacity is finite, there exists an extinction threshold for the predator population that separates a stable active two-species coexistence phase from an inactive state wherein only prey survive. Holding all other rates fixed, we investigate the non-equilibrium relaxation of the predator density in the vicinity of the critical predation rate. As expected, we observe critical slowing-down, i.e., a power law dependence of the relaxation time on the predation rate, and algebraic decay of the predator density at the extinction critical point. The numerically determined critical exponents are in accord with the established values of the directed percolation universality class. Following a sudden predation rate change to its critical value, one finds critical aging for the predator density autocorrelation function that is also governed by universal scaling exponents. This aging scaling signature of the active-to-absorbing state phase transition emerges at significantly earlier times than the stationary critical power laws, and could thus serve as an advanced indicator of the (predator) population’s proximity to its extinction threshold.

Development of an epiphyte indicator of nutrient enrichment ...

EPA Pesticide Factsheets

Metrics of epiphyte load on macrophytes were evaluated for use as quantitative biological indicators for nutrient impacts in estuarine waters, based on review and analysis of the literature on epiphytes and macrophytes, primarily seagrasses, but including some brackish and freshwater rooted macrophyte species. An approach is presented that empirically derives threshold epiphyte loads which are likely to cause specified levels of decrease in macrophyte response metrics such as biomass, shoot density, percent cover, production and growth. Data from 36 studies of 10 macrophyte species were pooled to derive relationships between epiphyte load and -25 and -50% seagrass response levels, which are proposed as the primary basis for establishment of critical threshold values. Given multiple sources of variability in the response data, threshold ranges based on the range of values falling between the median and the 75th quantiles of observations at a given seagrass response level are proposed rather than single, critical point values. Four epiphyte load threshold categories - low, moderate, high, very high, are proposed. Comparison of values of epiphyte loads associated with 25 and 50% reductions in light to macrophytes suggest that the threshold ranges are realistic both in terms of the principle mechanism of impact to macrophytes and in terms of the magnitude of resultant impacts expressed by the macrophytes. Some variability in response levels was observed among

Superallowed Beta Decay Studies at TRIUMF --- Nuclear Structure and Fundamental Symmetries

NASA Astrophysics Data System (ADS)

Zganjar, E. F.; Achtzehn, T.; Albers, D.; Andreoiu, C.; Andreyev, A. N.; Austin, R. A. E.; Ball, G. C.; Behr, J. A.; Biosvert, G. C.; Bricault, P.; Bishop, S.; Chakrawarthy, R. S.; Churchman, R.; Cross, D.; Cunningham, E.; D'Auria, J. M.; Dombsky, M.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hackman, G.; Hanemaayer, V.; Hardy, J. C.; Hodgson, D. F.; Hyland, B.; Iacob, V.; Klages, P.; Koopmans, K. A.; Kulp, W. D.; Lassen, J.; Lavoie, J. P.; Leslie, J. R.; Linder, T.; MacDonald, J. A.; Mak, H.-B.; Melconian, D.; Morton, A. C.; Ormand, W. E.; Osborne, C. J.; Pearson, C. J.; Pearson, M. R.; Phillips, A. A.; Piechaczek, A.; Ressler, J.; Sarazin, F.; Savard, G.; Schumaker, M. A.; Scraggs, H. C.; Svensson, C. E.; Valiente-Dobon, J. J.; Towner, I. S.; Waddington, J. C.; Walker, P. M.; Wendt, K.; Wood, J. L.

2007-04-01

Precision measurement of the beta -decay half-life, Q-value, and branching ratio between nuclear analog states of Jpi = 0+ and T=1 can provide critical and fundamental tests of the Standard Model's description of electroweak interactions. A program has been initiated at TRIUMF-ISAC to measure the ft values of these superallowed beta transitions. Two Tz = 0, A > 60 cases, 74Rb and 62Ga, are presented. These are particularly relevant because they can provide critical tests of the calculated nuclear structure and isospin-symmetry breaking corrections that are predicted to be larger for heavier nuclei, and because they demonstrate the advance in the experimental precision on ft at TRIUMF-ISAC from 0.26% for 74Rb in 2002 to 0.05% for 62Ga in 2006. The high precision world data on experimental ft and corrected Ft values are discussed and shown to be consistent with CVC at the 10-4 level, yielding an average Ft = 3073.70(74) s. This Ft leads to Vud = 0.9737(4) for the up-down element of the Standard Model's CKM matrix. With this value and the Particle Data Group's 2006 values for Vus and Vub, the unitarity condition for the CKM matrix is met. Additional measurements and calculations are needed, however, to reduce the uncertainties in that evaluation. That objective is the focus of the continuing program on superallowed-beta decay at TRIUMF-ISAC.

Forecasting neutrino masses from combining KATRIN and the CMB observations: Frequentist and Bayesian analyses

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

Host, Ole; Lahav, Ofer; Abdalla, Filipe B.

We present a showcase for deriving bounds on the neutrino masses from laboratory experiments and cosmological observations. We compare the frequentist and Bayesian bounds on the effective electron neutrino mass m{sub {beta}} which the KATRIN neutrino mass experiment is expected to obtain, using both an analytical likelihood function and Monte Carlo simulations of KATRIN. Assuming a uniform prior in m{sub {beta}}, we find that a null result yields an upper bound of about 0.17 eV at 90% confidence in the Bayesian analysis, to be compared with the frequentist KATRIN reference value of 0.20 eV. This is a significant difference whenmore » judged relative to the systematic and statistical uncertainties of the experiment. On the other hand, an input m{sub {beta}}=0.35 eV, which is the KATRIN 5{sigma} detection threshold, would be detected at virtually the same level. Finally, we combine the simulated KATRIN results with cosmological data in the form of present (post-WMAP) and future (simulated Planck) observations. If an input of m{sub {beta}}=0.2 eV is assumed in our simulations, KATRIN alone excludes a zero neutrino mass at 2.2{sigma}. Adding Planck data increases the probability of detection to a median 2.7{sigma}. The analysis highlights the importance of combining cosmological and laboratory data on an equal footing.« less

Enhancing creative cognition with a rapid right-parietal neurofeedback procedure.

PubMed

Agnoli, Sergio; Zanon, Marco; Mastria, Serena; Avenanti, Alessio; Corazza, Giovanni Emanuele

2018-02-14

The present article describes an innovative neurofeedback training (NFT) procedure aimed at increasing creative cognition through the enhancement of specific brain activities previously associated with divergent thinking. We designed and tested two NFT protocols based on training alpha and beta EEG oscillations selectively measured over the right parietal region. A total of 80 participants were involved, 40 in the alpha NFT protocol and 40 in the beta NFT protocol. The NFT loop was closed on a video stream that would advance only when oscillation power exceeded a normalized threshold. The total duration of the protocol was two hours in a single day, hence its classification as rapid. Changes in ideational fluency and originality, measured with a divergent thinking task, were compared between participants receiving real video feedback and participants receiving sham feedback. We controlled for individual differences in creative achievement level. Results showed that the protocols were effective at enhancing alpha and beta activities in the targeted area. Differences between the two protocols emerged in their effectiveness at promoting divergent thinking. While no significant changes in originality resulted from the rapid alpha NFT, increases in both originality and fluency emerged as a consequence of the rapid beta NFT. These results were particularly evident in participants starting with a low creative achievement level. Possible interpretations and future directions are proposed and discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exposure to biohazards in wood dust: bacteria, fungi, endotoxins, and (1-->3)-beta-D-glucans.

PubMed

Alwis, K U; Mandryk, J; Hocking, A D

1999-09-01

Personal exposure to fungi, bacteria, endotoxin, and (1-->3)-beta-D-glucan was determined at different woodworking sites--logging sites, sawmills, woodchipping sites, and joineries. Exposure levels to fungi at logging sites and sawmills were in the range of 10(3)-10(4) cfu/m3, at the woodchipping mill, 10(3)-10(5) cfu/m3, and at joineries, 10(2)-10(4) cfu/m3. Although mean endotoxin levels were lower than the suggested threshold value of 20 ng/m3, some personal exposures at sawmills and a joinery exceeded the standard. The geometric mean personal (1-->3)-beta-D-glucan exposure level at the woodchipping mill was 2.32 ng/m3, at sawmills, 1.37 ng/m3, at logging sites, 2.02 ng/m3, and at joineries, 0.43 ng/m3. Highly significant associations were found between mean personal inhalable endotoxin exposures and Gram-negative bacteria levels (p < 0.0001), and mean personal inhalable (1-->3)-beta-D-glucan exposures and fungi levels (p = 0.0003). The prevalence of cough, phlegm, chronic bronchitis, nasal symptoms, frequent headaches, and eye and throat irritations was significantly higher among woodworkers than controls. Dose-response relationships were found between personal exposures and work-related symptoms among joinery workers and sawmill and chip mill workers.

Three validation metrics for automated probabilistic image segmentation of brain tumours

PubMed Central

Zou, Kelly H.; Wells, William M.; Kikinis, Ron; Warfield, Simon K.

2005-01-01

SUMMARY The validity of brain tumour segmentation is an important issue in image processing because it has a direct impact on surgical planning. We examined the segmentation accuracy based on three two-sample validation metrics against the estimated composite latent gold standard, which was derived from several experts’ manual segmentations by an EM algorithm. The distribution functions of the tumour and control pixel data were parametrically assumed to be a mixture of two beta distributions with different shape parameters. We estimated the corresponding receiver operating characteristic curve, Dice similarity coefficient, and mutual information, over all possible decision thresholds. Based on each validation metric, an optimal threshold was then computed via maximization. We illustrated these methods on MR imaging data from nine brain tumour cases of three different tumour types, each consisting of a large number of pixels. The automated segmentation yielded satisfactory accuracy with varied optimal thresholds. The performances of these validation metrics were also investigated via Monte Carlo simulation. Extensions of incorporating spatial correlation structures using a Markov random field model were considered. PMID:15083482

Review of Neutrino Mass Measurements

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

Giuliani, A.; INFN-Milano, Via Valleggio 11, I-22100 Como

2006-02-08

After a brief summary of the recent achievements of neutrino physics, the concept of neutrino mass scale is clarified. The methods for the determination of the neutrino mass values are summarized and critically compared, in particular in the different and complementary contexts of cosmology, double and single beta decay. The attention is then focussed on the laboratory approaches to investigate neutrino mass. The role of neutrinoless double beta decay is explained and a short review of the present and most promising future experiments in this field is given. Single beta decay sensitivity is discussed, with brief descriptions of the KATRINmore » tritium experiment and of the recently proposed MARE rhenium project.« less

Assessing lead thresholds for phytotoxicity and potential dietary toxicity in selected vegetable crops.

PubMed

Hong, C L; Jia, Y B; Yang, X E; He, Z L; Stoffella, P J

2008-04-01

Lead tolerance and accumulation in shoots and edible parts varied with crop species and soil type. The critical Pb concentrations at 10% yield reduction were 24.71, 28.25, and 0.567 mg kg(-1) for pakchoi, celery, and hot pepper, respectively under hydroponic conditions, whereas were 13.1, 3.83, 0.734 mg kg(-1) grown in the Inceptisol and 31.7, 30.0, 0.854 mg kg(-1) in the Alluvial soil, respectively. Based on the threshold of human dietary toxicity for Pb, the critical levels of soil available Pb for pakchoi, celery, and hot pepper were 5.07, 8.06, and 0.48 mg kg(-1) for the Inceptisol, and 1.38, 1.47, and 0.162 mg kg(-1) for the Alluvial soil, respectively. Similarly, the total soil Pb thresholds were different from vegetable species and soil types.

Humans and seasonal climate variability threaten large-bodied coral reef fish with small ranges.

PubMed

Mellin, C; Mouillot, D; Kulbicki, M; McClanahan, T R; Vigliola, L; Bradshaw, C J A; Brainard, R E; Chabanet, P; Edgar, G J; Fordham, D A; Friedlander, A M; Parravicini, V; Sequeira, A M M; Stuart-Smith, R D; Wantiez, L; Caley, M J

2016-02-03

Coral reefs are among the most species-rich and threatened ecosystems on Earth, yet the extent to which human stressors determine species occurrences, compared with biogeography or environmental conditions, remains largely unknown. With ever-increasing human-mediated disturbances on these ecosystems, an important question is not only how many species can inhabit local communities, but also which biological traits determine species that can persist (or not) above particular disturbance thresholds. Here we show that human pressure and seasonal climate variability are disproportionately and negatively associated with the occurrence of large-bodied and geographically small-ranging fishes within local coral reef communities. These species are 67% less likely to occur where human impact and temperature seasonality exceed critical thresholds, such as in the marine biodiversity hotspot: the Coral Triangle. Our results identify the most sensitive species and critical thresholds of human and climatic stressors, providing opportunity for targeted conservation intervention to prevent local extinctions.

Light - Instead of UV Protection: New Requirements for Skin Cancer Prevention.

PubMed

Zastrow, Leonhard; Lademann, Jürgen

2016-03-01

The requirements on sunscreens have essentially changed, since some years ago it was demonstrated that approximately 50% of free radicals, that are formed in the skin by solar radiation, originate from the visible and infrared regions of the solar spectrum. In addition, a critical radical concentration threshold could be found. If this concentration, the free radical threshold value (FRTV), is exceeded, sunburn, immunosuppression and skin cancer may develop. Application of sunscreens and lotions protects against sunburn in the UV region of the solar spectrum and therefore is frequently used to extend people's stay in the sun. However, this behaviour can enhance the concentration of free radicals formed in the visible and infrared regions of the solar spectrum, so that the critical radical threshold is exceeded and the skin may be damaged. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Topological dimension tunes activity patterns in hierarchical modular networks

NASA Astrophysics Data System (ADS)

Safari, Ali; Moretti, Paolo; Muñoz, Miguel A.

2017-11-01

Connectivity patterns of relevance in neuroscience and systems biology can be encoded in hierarchical modular networks (HMNs). Recent studies highlight the role of hierarchical modular organization in shaping brain activity patterns, providing an excellent substrate to promote both segregation and integration of neural information. Here, we propose an extensive analysis of the critical spreading rate (or ‘epidemic’ threshold)—separating a phase with endemic persistent activity from one in which activity ceases—on diverse HMNs. By employing analytical and computational techniques we determine the nature of such a threshold and scrutinize how it depends on general structural features of the underlying HMN. We critically discuss the extent to which current graph-spectral methods can be applied to predict the onset of spreading in HMNs and, most importantly, we elucidate the role played by the network topological dimension as a relevant and unifying structural parameter, controlling the epidemic threshold.

New method for measuring the laser-induced damage threshold of optical thin film

NASA Astrophysics Data System (ADS)

Su, Jun-hong; Wang, Hong; Xi, Ying-xue

2012-10-01

The laser-induced damage threshold (LIDT) of thin film means that the thin film can withstand a maximum intensity of laser radiation. The film will be damaged when the irradiation under high laser intensity is greater than the value of LIDT. In this paper, an experimental platform with measurement operator interfaces and control procedures in the VB circumstance is built according to ISO11254-1. In order to obtain more accurate results than that with manual measurement, in the software system, a hardware device can be controlled by control widget on the operator interfaces. According to the sample characteristic, critical parameters of the LIDT measurement system such as spot diameter, damage threshold region, and critical damage pixel number are set up on the man-machine conversation interface, which could realize intelligent measurements of the LIDT. According to experimental data, the LIDT is obtained by fitting damage curve automatically.

Measurements of electron detection efficiencies in solid state detectors.

NASA Technical Reports Server (NTRS)

Lupton, J. E.; Stone, E. C.

1972-01-01

Detailed laboratory measurement of the electron response of solid state detectors as a function of incident electron energy, detector depletion depth, and energy-loss discriminator threshold. These response functions were determined by exposing totally depleted silicon surface barrier detectors with depletion depths between 50 and 1000 microns to the beam from a magnetic beta-ray spectrometer. The data were extended to 5000 microns depletion depth using the results of previously published Monte Carlo electron calculations. When the electron counting efficiency of a given detector is plotted as a function of energy-loss threshold for various incident energies, the efficiency curves are bounded by a smooth envelope which represents the upper limit to the detection efficiency. These upper limit curves, which scale in a simple way, make it possible to easily estimate the electron sensitivity of solid-state detector systems.

Marginal instability threshold of magnetosonic waves in kappa distributed plasma

NASA Astrophysics Data System (ADS)

Bashir, M. F.; Manzoor, M. Z.; Ilie, R.; Yoon, P. H.; Miasli, M. S.

2017-12-01

The dispersion relation of magnetosonic wave is studied taking the non-extensive anisotropic counter-streaming distribution which follows the Tsallis statistics. The effects of non-extensivity parameter (q), counter-streaming parameter (P) and the wave-particle interaction is analyzed on the growth rate and the marginal instability threshold condition of Magnetosonic (MS) mode to provide the possible explanation of different regions the Bale-diagram obtained from the solar wind data at 1 AU as represented by the temperature anisotropy ( ) vs plasma beta ( ) solar wind data plot. It is shown that the most of the regions of Bale-diagram is bounded by the MS instability under different condition and best fitted by the non-extesnive distribution. The results for the bi-kappa distribution and bi- Maxwellian distribution are also obtained in the limits and respectively.

Analyzing threshold pressure limitations in microfluidic transistors for self-regulated microfluidic circuits.

PubMed

Kim, Sung-Jin; Yokokawa, Ryuji; Takayama, Shuichi

2012-12-03

This paper reveals a critical limitation in the electro-hydraulic analogy between a microfluidic membrane-valve (μMV) and an electronic transistor. Unlike typical transistors that have similar on and off threshold voltages, in hydraulic μMVs, the threshold pressures for opening and closing are significantly different and can change, even for the same μMVs depending on overall circuit design and operation conditions. We explain, in particular, how the negative values of the closing threshold pressures significantly constrain operation of even simple hydraulic μMV circuits such as autonomously switching two-valve microfluidic oscillators. These understandings have significant implications in designing self-regulated microfluidic devices.

A new characterization of three-dimensional conductivity backbone above and below the percolation threshold

NASA Astrophysics Data System (ADS)

Skal, Asya S.

1996-08-01

A new definition of three-dimensional conductivity backbone, obtained from a distribution function of Joule heat and the Hall coefficient is introduced. The fractal dimension d fB = d - ( {g}/{v}) = 2.25 of conductivity backbone for both sides of the threshold is obtained from a critical exponent of the Hall coefficient g = 0.6. This allows one to construct, below the threshold, a new order parameter of metal-conductor transition—the two-component infinite conductivity back-bone and tested scaling relation, proposed by Alexander and Orbach [ J. Phys. Rev. Lett.43, 1982, L625] for both sides of a threshold.

Inhibition by Chondroitin Sulfate E Can Specify Functional Wnt/β-Catenin Signaling Thresholds in NIH3T3 Fibroblasts*

PubMed Central

Willis, Catherine M.; Klüppel, Michael

2012-01-01

Aberrant activation of the Wnt/β-catenin signaling pathway is frequently associated with human disease, including cancer, and thus represents a key therapeutic target. However, Wnt/β-catenin signaling also plays critical roles in many aspects of normal adult tissue homeostasis. The identification of mechanisms and strategies to selectively inhibit the disease-related functions of Wnt signaling, while preserving normal physiological functions, is in its infancy. Here, we report the identification of exogenous chondroitin sulfate-E (CS-E) as an inhibitor of specific molecular and biological outcomes of Wnt3a signaling in NIH3T3 fibroblasts. We demonstrate that CS-E can decrease Wnt3a signaling through the negative regulation of LRP6 receptor activation. However, this inhibitory effect of CS-E only affected Wnt3a-mediated induction, but not repression, of target gene expression. We went on to identify a critical Wnt3a signaling threshold that differentially affects target gene induction versus repression. This signaling threshold also controlled the effects of Wnt3a on proliferation and serum starvation-induced apoptosis. Limiting Wnt3a signaling to this critical threshold, either by CS-E treatment or by ligand dilution, interfered with Wnt3a-mediated stimulation of proliferation but did not impair Wnt3a-mediated reduction of serum starvation-induced apoptosis. Treatment with pharmacological inhibitors demonstrated that both induction and repression of Wnt3a target genes in NIH3T3 cells require the canonical Wnt/β-catenin signaling cascade. Our data establish the feasibility of selective inhibition of Wnt/β-catenin transcriptional programs and biological outcomes through the exploitation of intrinsic signaling thresholds. PMID:22915582

Mechanisms of integrin-vascular endothelial growth factor receptor cross-activation in angiogenesis.

PubMed

Mahabeleshwar, Ganapati H; Feng, Weiyi; Reddy, Kumar; Plow, Edward F; Byzova, Tatiana V

2007-09-14

The functional responses of endothelial cells are dependent on signaling from peptide growth factors and the cellular adhesion receptors, integrins. These include cell adhesion, migration, and proliferation, which, in turn, are essential for more complex processes such as formation of the endothelial tube network during angiogenesis. This study identifies the molecular requirements for the cross-activation between beta3 integrin and tyrosine kinase receptor 2 for vascular endothelial growth factor (VEGF) receptor (VEGFR-2) on endothelium. The relationship between VEGFR-2 and beta3 integrin appears to be synergistic, because VEGFR-2 activation induces beta3 integrin tyrosine phosphorylation, which, in turn, is crucial for VEGF-induced tyrosine phosphorylation of VEGFR-2. We demonstrate here that adhesion- and growth factor-induced beta3 integrin tyrosine phosphorylation are directly mediated by c-Src. VEGF-stimulated recruitment and activation of c-Src and subsequent beta3 integrin tyrosine phosphorylation are critical for interaction between VEGFR-2 and beta3 integrin. Moreover, c-Src mediates growth factor-induced beta3 integrin activation, ligand binding, beta3 integrin-dependent cell adhesion, directional migration of endothelial cells, and initiation of angiogenic programming in endothelial cells. Thus, the present study determines the molecular mechanisms and consequences of the synergism between 2 cell surface receptor systems, growth factor receptor and integrins, and opens new avenues for the development of pro- and antiangiogenic strategies.

Fibrinogen variant B[beta]D432A has normal polymerization but does not bind knob 'B'

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

Bowley, Sheryl R.; Lord, Susan T.; UNC)

2009-10-23

Fibrinogen residue B{beta}432Asp is part of hole 'b' that interacts with knob 'B,' whose sequence starts with Gly-His-Arg-Pro-amide (GHRP). Because previous studies showed B{beta}D432A has normal polymerization, we hypothesized that B{beta}432Asp is not critical for knob 'B' binding and that new knob-hole interactions would compensate for the loss of this Asp residue. To test this hypothesis, we solved the crystal structure of fragment D from B{beta}D432A. Surprisingly, the structure (rfD-B{beta}D432A+GH) showed the peptide GHRP was not bound to hole 'b.' We then re-evaluated the polymerization of this variant by examining clot turbidity, clot structure, and the rate of FXIIIa cross-linking.more » The turbidity and the rate of - dimer formation for B{beta}D432A were indistinguishable compared with normal fibrinogen. Scanning electron microscopy showed no significant differences between the clots of B{beta}D432A and normal, but the thrombin-derived clots had thicker fibers than clots obtained from batroxobin, suggesting that cleavage of FpB is more important than 'B:b' interactions. We conclude that hole 'b' and 'B:b' knob-hole binding per se have no influence on fibrin polymerization.« less

Ligand-Dependent Disorder of Loop Observed in Extended-Spectrum SHV-Type beta-Lactamase

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

J Sampson; W Ke; C Bethel

2011-12-31

Among Gram-negative bacteria, resistance to {beta}-lactams is mediated primarily by {beta}-lactamases (EC 3.2.6.5), periplasmic enzymes that inactivate {beta}-lactam antibiotics. Substitutions at critical amino acid positions in the class A {beta}-lactamase families result in enzymes that can hydrolyze extended-spectrum cephalosporins, thus demonstrating an 'extended-spectrum' {beta}-lactamase (ESBL) phenotype. Using SHV ESBLs with substitutions in the {Omega} loop (R164H and R164S) as target enzymes to understand this enhanced biochemical capability and to serve as a basis for novel {beta}-lactamase inhibitor development, we determined the spectra of activity and crystal structures of these variants. We also studied the inactivation of the R164H and R164Smore » mutants with tazobactam and SA2-13, a unique {beta}-lactamase inhibitor that undergoes a distinctive reaction chemistry in the active site. We noted that the reduced K{sub i} values for the R164H and R164S mutants with SA2-13 are comparable to those with tazobactam (submicromolar). The apo enzyme crystal structures of the R164H and R164S SHV variants revealed an ordered {Omega} loop architecture that became disordered when SA2-13 was bound. Important structural alterations that result from the binding of SA2-13 explain the enhanced susceptibility of these ESBL enzymes to this inhibitor and highlight ligand-dependent {Omega} loop flexibility as a mechanism for accommodating and hydrolyzing {beta}-lactam substrates.« less

Elevated plasma TGF-beta1 in renal diseases: cause or consequence?

PubMed

Junker, U; Haufe, C C; Nuske, K; Rebstock, K; Steiner, T; Wunderlich, H; Junker, K; Reinhold, D

2000-07-01

We previously reported elevated levels of TGF-beta1 in patients with renal carcinoma. Certain aspects led us to ask whether they might be caused by chronic damage to the kidney(s). Here we report on an extended set of patients with various renal diseases, lung cancer, humoral immunodeficiency and controls. For latent TGF-beta1 in plasma, we find that the control, immunodeficiency, lung cancer and kidney transplant groups do not differ significantly (means, 7.0-8.8 ng/ml). Also, acute short-term renal stress (extracorporal lithotrypsy) does not lead to an increase of TGF-beta1. However, the pyelonephritis patients present with levels of 19.0 ng/ml, chronic extracorporal dialysis patients with 15.5 ng/ml, and renal cell carcinoma patients with 22.8 ng/ml. For active TGF-beta1 these findings are exactly recovered. For serum levels, only the renal carcinoma group presents with significantly elevated levels of TGF-beta1. Kidney transplantation seems to normalize TGF-beta1 levels, while in the kidney cancer patients surgery has an effect only in part of the group. We conclude that elevated plasma TGF-beta1 levels are common in at least two chronic renal disease conditions, and that it normalizes with restoration of renal function. It is tempting to speculate that chronic elevation of TGF-beta1 in these patients may be critically involved in these conditions predisposing to renal cancer. Copyright 2000 Academic Press.

Cellular demise and inflammatory microglial activation during beta-amyloid toxicity are governed by Wnt1 and canonical signaling pathways.

PubMed

Chong, Zhao Zhong; Li, Faqi; Maiese, Kenneth

2007-06-01

Initially described as a modulator of embryogenesis for a number of organ systems, Wnt1 has recently been linked to the development of several neurodegenerative disorders, none being of greater significance than Alzheimer's disease. We therefore examined the ability of Wnt1 to oversee vital pathways responsible for cell survival during beta-amyloid (Abeta1-42) exposure. Here we show that Wnt1 is critical for protection in the SH-SY5Y neuronal cell line against genomic DNA degradation, membrane phosphatidylserine (PS) exposure, and microglial activation, since these neuroprotective attributes of Wnt1 are lost during gene silencing of Wnt1 protein expression. Intimately tied to Wnt1 protection is the presence and activation of Akt1. Pharmacological inhibition of the PI 3-K pathway or gene silencing of Akt1 expression can abrogate the protective capacity of Wnt1. Closely aligned with Wnt1 and Akt1 are the integrated canonical pathways of synthase kinase-3beta (GSK-3beta) and beta-catenin. Through Akt1 dependent pathways, Wnt1 phosphorylates GSK-3beta and maintains beta-catenin integrity to insure its translocation from the cytoplasm to the nucleus to block apoptosis. Our work outlines a highly novel role for Wnt1 and its integration with Akt1, GSK-3beta, and beta-catenin to foster neuronal cell survival and repress inflammatory microglial activation that can identify new avenues of therapy against neurodegenerative disorders.

Critical levels as applied to ozone for North American forests

Treesearch

Robert C. Musselman

2006-01-01

The United States and Canada have used concentration-based parameters for air quality standards for ozone effects on forests in North America. The European critical levels method for air quality standards uses an exposure-based parameter, a cumulative ozone concentration index with a threshold cutoff value. The critical levels method has not been used in North America...

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

PubMed

Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

Structure-activity relationships of N-beta-phenylpropionyl-L-tyrosine and its derivatives on the inhibition of an identifiable giant neurone of an African giant snail (Achatina fulica Férussac).

PubMed Central

Ariyoshi, Y.; Takeuchi, H.

1982-01-01

1 Inhibitory effects of N-beta-phenylpropionyl-L-tyrosine, N-beta-phenylpropionyl-L-tryptophan and their derivatives on an identifiable giant neurone, TAN (tonically autoactive neurone) of an African giant snail (Achatina fulica Férussac) were examined in an attempt to elucidate which structural features are necessary to produce the effect. 2 Of the compounds examined, N-beta-cyclohexylpropionyl-L-tyrosine showed the strongest effect. Its critical concentration (c.c.) was 3 X 10(-8)-10(-7)M, about ten times lower than that of N-beta-phenylpropionyl-L-tyrosine (c.c., 3 X 10(-7)-10(-6)M). N-beta-cyclohexylpropionyl-L-tryptophan (c.c., 10(-6)M) had an effect almost similar to that of N-beta-phenylpropionyl-L-tryptophan (c.c., 10(-6)M). 3 N-beta-Phenylpropionyl-N-methyl-L-tyrosine had no effect at a high concentration. 4 Effects of N-beta-phenylpropionyl-L-tyrosine amide (c.c., 3 X 10(-7)-10(-6)M) and N-beta-phenylpropionyl-L-tryptophan amide (c.c., 10(-6)M) were very similar to those of N-beta-phenylpropionyl-L-tyrosine and N-beta-phenylpropionyl-L-tryptophan respectively. 5 N-beta-Phenylpropionyl-p-amino-L-phenylalanine (c.c., 3 X 10(-5)-10(-4)M) and N-beta-phenylpropionyl-p-chloro-L-phenylalanine (c.c., 10(-4)M) had only a weak effect. 6 It is proposed that the structural features producing the effect are as follows: the active compound has a phenyl or a cyclohexyl group (hydrophobic binding group), after a suitable distance a peptide bond (proton donor and proton acceptor), adjacently a carbonyl group (proton acceptor), and a phenolic hydroxyl or an indolyl imino group (proton donor) in the molecule. PMID:7150871

The effect of a beta-lactamase inhibitor peptide on bacterial membrane structure and integrity: a comparative study.

PubMed

Alaybeyoglu, Begum; Uluocak, Bilge Gedik; Akbulut, Berna Sariyar; Ozkirimli, Elif

2017-05-01

Co-administration of beta-lactam antibiotics and beta-lactamase inhibitors has been a favored treatment strategy against beta-lactamase-mediated bacterial antibiotic resistance, but the emergence of beta-lactamases resistant to current inhibitors necessitates the discovery of novel non-beta-lactam inhibitors. Peptides derived from the Ala46-Tyr51 region of the beta-lactamase inhibitor protein are considered as potent inhibitors of beta-lactamase; unfortunately, peptide delivery into the cell limits their potential. The properties of cell-penetrating peptides could guide the design of beta-lactamase inhibitory peptides. Here, our goal is to modify the peptide with the sequence RRGHYY that possesses beta-lactamase inhibitory activity under in vitro conditions. Inspired by the work on the cell-penetrating peptide pVEC, our approach involved the addition of the N-terminal hydrophobic residues, LLIIL, from pVEC to the inhibitor peptide to build a chimera. These residues have been reported to be critical in the uptake of pVEC. We tested the potential of RRGHYY and its chimeric derivative as a beta-lactamase inhibitory peptide on Escherichia coli cells and compared the results with the action of the antimicrobial peptide melittin, the beta-lactam antibiotic ampicillin, and the beta-lactamase inhibitor potassium clavulanate to get mechanistic details on their action. Our results show that the addition of LLIIL to the N-terminus of the beta-lactamase inhibitory peptide RRGHYY increases its membrane permeabilizing potential. Interestingly, the addition of this short stretch of hydrophobic residues also modified the inhibitory peptide such that it acquired antimicrobial property. We propose that addition of the hydrophobic LLIIL residues to the peptide N-terminus offers a promising strategy to design novel antimicrobial peptides in the battle against antibiotic resistance. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Supramolecular self-assemblies of beta-cyclodextrins with aromatic tethers: factors governing the helical columnar versus linear channel superstructures.

PubMed

Liu, Yu; Fan, Zhi; Zhang, Heng-Yi; Yang, Ying-Wei; Ding, Fei; Liu, Shuang-Xi; Wu, Xue; Wada, Takehiko; Inoue, Yoshihisa

2003-10-31

A series of 6-O-(p-substituted phenyl)-modified beta-cyclodextrin derivatives, i.e., 6-O-(4-bromophenyl)-beta-CD (1), 6-O-(4-nitrophenyl)-beta-CD (2), 6-O-(4-formylphenyl)-beta-CD (3), 6-phenylselenyl-6-deoxy-beta-CD (4), and 6-O-(4-hydroxybenzoyl)-beta-CD (5), were synthesized, and their inclusion complexation behavior in aqueous solution and self-assembling behavior in the solid state were comparatively studied by NMR spectroscopy, microcalorimetry, crystallography, and scanning tunneling microscopy. Interestingly, (seleno)ethers 1-4 and ester 5 displayed distinctly different self-assembling behavior in the solid state, affording a successively threading head-to-tail polymeric helical structure for the (seleno)ethers or a mutually penetrating tail-to-tail dimeric columnar channel structure for the ester. Combining the present and previous structures reported for the relevant beta-CD derivatives, we further deduce that the pivot heteroatom, through which the aromatic substituent is tethered to beta-CD, plays a critical role in determining the helix structure, endowing the 2-fold and 4-fold axes to the N/O- and S/Se-pivoted beta-CD aggregates, respectively. This means that one can control the self-assembling orientation, alignment, and helicity in the solid state by finely tuning the pivot atom and the tether length. Further NMR and calorimetric studies on the self-assembling behavior in aqueous solution revealed that the dimerization step is the key to the formation of linear polymeric supramolecular architecture, which is driven by favorable entropic contributions.

Smad signaling pathway is a pivotal component of tissue inhibitor of metalloproteinases-3 regulation by transforming growth factor beta in human chondrocytes.

PubMed

Qureshi, Hamid Yaqoob; Ricci, Gemma; Zafarullah, Muhammad

2008-09-01

Transforming growth factor beta (TGF-beta1) promotes cartilage matrix synthesis and induces tissue inhibitor of metalloproteinases-3 (TIMP-3), which inhibits matrix metalloproteinases, aggrecanases and TNF-alpha-converting enzyme implicated in articular cartilage degradation and joint inflammation. TGF-beta1 activates Akt, ERK and Smad2 pathways in chondrocytes. Here we investigated previously unexplored roles of specific Smads in TGF-beta1 induction of TIMP-3 gene by pharmacological and genetic knockdown approaches. TGF-beta1-induced Smad2 phosphorylation and TIMP-3 protein expression could be inhibited by the Smad2/3 phosphorylation inhibitors, PD169316 and SB203580 and by Smad2-specific siRNA. Specific inhibitor of Smad3 (SIS3) and Smad3 siRNA abolished TGF-beta induction of TIMP-3. Smad2/3 siRNAs also down regulated TIMP-3 promoter-driven luciferase activities, suggesting transcriptional regulation. SiRNA-driven co-Smad4 knockdown abrogated TIMP-3 augmentation by TGF-beta. TIMP-3 promoter deletion analysis revealed that -828 deletion retains the original promoter activity while -333 and -167 deletions display somewhat reduced activity suggesting that most of the TGF-beta-responsive, cis-acting elements are found in the -333 fragment. Chromatin Immunoprecipitation (ChIP) analysis confirmed binding of Smad2 and Smad4 with the -940 and -333 promoter sequences. These results suggest that receptor-activated Smad2 and Smad3 and co-Smad4 critically mediate TGF-beta-stimulated TIMP-3 expression in human chondrocytes and TIMP-3 gene is a target of Smad signaling pathway.

Jump conditions in transonic equilibria

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

Guazzotto, L.; Betti, R.; Jardin, S. C.

2013-04-15

In the present paper, the numerical calculation of transonic equilibria, first introduced with the FLOW code in Guazzotto et al.[Phys. Plasmas 11, 604 (2004)], is critically reviewed. In particular, the necessity and effect of imposing explicit jump conditions at the transonic discontinuity are investigated. It is found that 'standard' (low-{beta}, large aspect ratio) transonic equilibria satisfy the correct jump condition with very good approximation even if the jump condition is not explicitly imposed. On the other hand, it is also found that high-{beta}, low aspect ratio equilibria require the correct jump condition to be explicitly imposed. Various numerical approaches aremore » described to modify FLOW to include the jump condition. It is proved that the new methods converge to the correct solution even in extreme cases of very large {beta}, while they agree with the results obtained with the old implementation of FLOW in lower-{beta} equilibria.« less

Standardization of haematology critical results management in adults: an International Council for Standardization in Haematology, ICSH, survey and recommendations.

PubMed

Keng, T B; De La Salle, B; Bourner, G; Merino, A; Han, J-Y; Kawai, Y; Peng, M T; McCafferty, R

2016-10-01

These recommendations are intended to develop a consensus in the previously published papers as to which parameters and what values should be considered critical. A practical guide on the standardization of critical results management in haematology laboratories would be beneficial as part of good laboratory and clinical practice and for use by laboratory-accrediting agencies. A working group with members from Europe, America, Australasia and Asia was formed by International Council for Standardization in Haematology. A pattern of practice survey of 21 questions was distributed in 2014, and the data were collected electronically by Survey Monkey. The mode, or most commonly occurring value, was selected as the threshold for the upper and lower alert limits for critical results reporting. A total of 666 laboratories submitted data to this study and, of these, 499 submitted complete responses. Full blood count critical results alert thresholds, morphology findings that trigger critical result notification, critical results alert list, notification process and maintenance of critical results management protocol are described. This international survey provided a snapshot of the current practice worldwide and has identified the existence of considerable heterogeneity of critical results management. The recommendations in this study represent a consensus of good laboratory practice. They are intended to encourage the implementation of a standardized critical results management protocol in the laboratory. © 2016 John Wiley & Sons Ltd.

Status and prospects of the SNO+ experiment

NASA Astrophysics Data System (ADS)

Maneira, J.

2016-05-01

The SNO+ experiment is located at the SNOLAB underground laboratory and will employ 780 tons of liquid scintillator loaded, in its initial phase, with 800 kg of 130Te (0.3% by mass) for a low-background and high-isotope-mass search for neutrino-less double beta decay. SNO+ reuses the acrylic vessel and PMT array of the SNO detector, but several experimental upgrades and adaptations were necessary to allow for the use of liquid scintillator. The SNO+ technique allows a staged approach, and extensive R&D is ongoing to increase the loadings and improve the purification of Tellurium. The very good conditions of background and low energy threshold allow SNO+ to also have other physics topics in its program, including geo- and reactor neutrinos, Supernova and solar neutrinos. This talk will describe the main advantages and challenges of the SNO+ approach for the double-beta decay program, the current status of the experiment and its sensitivity prospects.

Strongly screening corrections to antineutrino energy loss by β --decay of nuclides 53Fe, 54Fe, 55Fe, and 56Fe in supernova

NASA Astrophysics Data System (ADS)

Liu, Jing-Jing; Liu, Dong-Mei

2018-06-01

Based on the p-f shell-model, we discuss and calculate β--decay half-lives of neutron-rich nuclei, with a consideration of shell and pair effects, the decay energy, and the nucleon numbers. According to the linear response theory model, we study the effect of electron screening on the electron energy, beta-decay threshold energy, and the antineutrino energy loss rate by β--decay of some iron isotopes. We find that the electron screening antineutrino energy loss rates increase by about two orders of magnitude due to the shell effects and the pairing effect. Beta-decay rates with Q-value corrections due to strong electron screening are higher than those without the Q-value corrections by more than two orders of magnitude. Our conclusions may be helpful for the research on numerical simulations of the cooling of stars.

Critical phenomena in the general spherically symmetric Einstein-Yang-Mills system

NASA Astrophysics Data System (ADS)

Maliborski, Maciej; Rinne, Oliver

2018-02-01

We study critical behavior in gravitational collapse of a general spherically symmetric Yang-Mills field coupled to the Einstein equations. Unlike the magnetic ansatz used in previous numerical work, the general Yang-Mills connection has two degrees of freedom in spherical symmetry. This fact changes the phenomenology of critical collapse dramatically. The magnetic sector features both type I and type II critical collapse, with universal critical solutions. In contrast, in the general system type I disappears and the critical behavior at the threshold between dispersal and black hole formation is always type II. We obtain values of the mass scaling and echoing exponents close to those observed in the magnetic sector, however we find some indications that the critical solution differs from the purely magnetic discretely self-similar attractor and exact self-similarity and universality might be lost. The additional "type III" critical phenomenon in the magnetic sector, where black holes form on both sides of the threshold but the Yang-Mills potential is in different vacuum states and there is a mass gap, also disappears in the general system. We support our dynamical numerical simulations with calculations in linear perturbation theory; for instance, we compute quasi-normal modes of the unstable attractor (the Bartnik-McKinnon soliton) in type I collapse in the magnetic sector.

A proteomics strategy to discover beta-glucosidases from Aspergillus fumigatus with two-dimensional page in-gel activity assay and tandem mass spectrometry.

PubMed

Kim, Kee-Hong; Brown, Kimberly M; Harris, Paul V; Langston, James A; Cherry, Joel R

2007-12-01

Economically competitive production of ethanol from lignocellulosic biomass by enzymatic hydrolysis and fermentation is currently limited, in part, by the relatively high cost and low efficiency of the enzymes required to hydrolyze cellulose to fermentable sugars. Discovery of novel cellulases with greater activity could be a critical step in overcoming this cost barrier. beta-Glucosidase catalyzes the final step in conversion of glucose polymers to glucose. Despite the importance, only a few beta-glucosidases are commercially available, and more efficient ones are clearly needed. We developed a proteomics strategy aiming to discover beta-glucosidases present in the secreted proteome of the cellulose-degrading fungus Aspergillus fumigatus. With the use of partial or complete protein denaturing conditions, the secretory proteome was fractionated in a 2DGE format and beta-glucosidase activity was detected in the gel after infusion with a substrate analogue that fluoresces upon hydrolysis. Fluorescing spots were subjected to tryptic-digestion, and identification as beta-glucosidases was confirmed by tandem mass spectrometry. Two novel beta-glucosidases of A. fumigatus were identified by this in situ activity staining method, and the gene coding for a novel beta-glucosidase ( EAL88289 ) was cloned and heterologously expressed. The expressed beta-glucosidase showed far superior heat stability to the previously characterized beta-glucosidases of Aspergillus niger and Aspergillus oryzae. Improved heat stability is important for development of the next generation of saccharifying enzymes capable of performing fast cellulose hydrolysis reactions at elevated temperatures, thereby lowering the cost of bioethanol production. The in situ activity staining approach described here would be a useful tool for cataloguing and assessing the efficiency of beta-glucosidases in a high throughput fashion.

Critical analysis of the discrepancy between V(beta) and V(ss) for drugs exhibiting different two-compartment disposition profiles.

PubMed

Sobol, Eyal; Bialer, Meir

2005-03-01

It is well known that in the two-compartment open body model the values of apparent volume of distribution (V(beta)) and volume of distribution at steady state (V(ss)) are never identical. There are at least two conditions when V(beta) significantly overestimates V(ss). The first is when most of a drug is eliminated relatively rapidly but a small fraction of the dose persists and gives rise to an extremely long half-life. The second is when a drug is rapidly cleared from the central compartment with a short half-life. The primary purpose of the current paper was to investigate how different two-compartment disposition profiles affect the magnitude of difference between V(beta) and V(ss). Novel equations have been developed that relate the V(beta)/V(ss) ratio to f1 (fraction of drug elimination associated with the distributive phase) and to beta/alpha (ratio of the exponential coefficients). This paper demonstrates mathematically that an increasing value of f1 is associated with a greater divergence between V(beta) and V(ss). A similar relationship was also found for the divergence between the terminal half-life (t(1/2beta)) and the mean residence time (MRT). An increase in the beta/alpha ratio results in a substantial decrease of this discrepancy and provides a maximal possible value, or an upper limit to the V(beta)/V(ss) ratio. The newly derived equations along with their graphical presentation may serve as an excellent predictive tool for checking the accuracy of the experimentally obtained values of V(beta) and V(ss). Copyright 2004 John Wiley & Sons, Ltd.

Nanoscale organization of {beta}{sub 2}-adrenergic receptor-Venus fusion protein domains on the surface of mammalian cells

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

Vobornik, Dusan; Rouleau, Yanouchka; Haley, Jennifer

2009-04-24

Adrenergic receptors are a key component of nanoscale multiprotein complexes that are responsible for controlling the beat rate in a mammalian heart. We demonstrate the ability of near-field scanning optical microscopy (NSOM) to visualize {beta}{sub 2}-adrenergic receptors ({beta}{sub 2}AR) fused to the GFP analogue Venus at the nanoscale on HEK293 cells. The expression of the {beta}{sub 2}AR-Venus fusion protein was tightly controlled using a tetracycline-induced promoter. Both the size and density of the observed nanoscale domains are dependent on the level of induction and thus the level of protein expression. At concentrations between 100 and 700 ng/ml of inducer doxycycline,more » the size of domains containing the {beta}{sub 2}AR-Venus fusion protein appears to remain roughly constant, but the number of domains per cell increase. At 700 ng/ml doxycycline the functional receptors are organized into domains with an average diameter of 150 nm with a density similar to that observed for the native protein on primary murine cells. By contrast, larger micron-sized domains of {beta}{sub 2}AR are observed in the membrane of the HEK293 cells that stably overexpress {beta}{sub 2}AR-GFP and {beta}{sub 2}AR-eYFP. We conclude that precise chemical control of gene expression is highly advantageous for the use {beta}{sub 2}AR-Venus fusion proteins as models for {beta}{sub 2}AR function. These observations are critical for designing future cell models and assays based on {beta}{sub 2}AR, since the receptor biology is consistent with a relatively low density of nanoscale receptor domains.« less

How beta diversity and the underlying causes vary with sampling scales in the Changbai mountain forests.

PubMed

Tan, Lingzhao; Fan, Chunyu; Zhang, Chunyu; von Gadow, Klaus; Fan, Xiuhua

2017-12-01

This study aims to establish a relationship between the sampling scale and tree species beta diversity temperate forests and to identify the underlying causes of beta diversity at different sampling scales. The data were obtained from three large observational study areas in the Changbai mountain region in northeastern China. All trees with a dbh ≥1 cm were stem-mapped and measured. The beta diversity was calculated for four different grain sizes, and the associated variances were partitioned into components explained by environmental and spatial variables to determine the contributions of environmental filtering and dispersal limitation to beta diversity. The results showed that both beta diversity and the causes of beta diversity were dependent on the sampling scale. Beta diversity decreased with increasing scales. The best-explained beta diversity variation was up to about 60% which was discovered in the secondary conifer and broad-leaved mixed forest (CBF) study area at the 40 × 40 m scale. The variation partitioning result indicated that environmental filtering showed greater effects at bigger grain sizes, while dispersal limitation was found to be more important at smaller grain sizes. What is more, the result showed an increasing explanatory ability of environmental effects with increasing sampling grains but no clearly trend of spatial effects. The study emphasized that the underlying causes of beta diversity variation may be quite different within the same region depending on varying sampling scales. Therefore, scale effects should be taken into account in future studies on beta diversity, which is critical in identifying different relative importance of spatial and environmental drivers on species composition variation.

Spatially implicit approaches to understand the manipulation of mating success for insect invasion management

Treesearch

Takehiko Yamanaka; Andrew M. Liebhold

2009-01-01

Recent work indicates that Allee effects (the positive relationship between population size and per capita growth rate) are critical in determining the successful establishment of invading species. Allee effects may create population thresholds, and failure to establish is likely if invading populations fall below these thresholds. There are many mechanisms that may...

Vocabulary Acquisition in L2: Does CALL Really Help?

ERIC Educational Resources Information Center

Averianova, Irina

2015-01-01

Language competence in various communicative activities in L2 largely depends on the learners' size of vocabulary. The target vocabulary of adult L2 learners should be between 2,000 high frequency words (a critical threshold) and 10,000 word families (for comprehension of university texts). For a TOEIC test, the threshold is estimated to be…

Spontaneous healing and growth of locked magnetic island chains in toroidal plasmas

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

Fitzpatrick, R.; Waelbroeck, F. L.

2012-11-15

Recent experiments have demonstrated that locked magnetic island chains in stellarator plasmas spontaneously heal under certain conditions, and spontaneously grow under others. A formalism initially developed to study magnetic island dynamics in tokamak plasmas is employed to investigate this phenomenon. It is found that island healing/growth transitions can be caused either by a breakdown in torque balance in the vicinity of the island chain, or by an imbalance between the various terms in the island width evolution equation. The scaling of the healing/growth thresholds with the standard dimensionless plasma parameters {beta}, {nu}{sub *}, and {rho}{sub *} is determined. In accordancemore » with the experimental data, it is found that island healing generally occurs at high {beta} and low {nu}{sub *}, and island growth at low {beta} and high {nu}{sub *}. In further agreement, it is found that island healing is accompanied an ion poloidal velocity shift in the electron diamagnetic direction, and island growth by a velocity shift in the ion diamagnetic direction. Finally, it is found that there is considerable hysteresis in the healing/growth cycle, as is also seen experimentally.« less

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

PubMed

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

2005-04-01

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

Subtle Ecological Gradient in the Tropics Triggers High Species-Turnover in a Local Geographical Scale

PubMed Central

Nguyen, Dinh T.

2016-01-01

Our perception of diversity, including both alpha- and beta-diversity components, depends on spatial scale. Studies of spatial variation of the latter are just starting, with a paucity of research on beta-diversity patterns at smaller scales. Understanding these patterns and the processes shaping the distribution of diversity is critical to describe this diversity, but it is paramount in conservation too. Here, we investigate the diversity and structure of a tropical community of herbivorous beetles at a reduced local scale of some 10 km2, evaluating the effect of a small, gradual ecological change on this structure. We sampled leaf beetles in the Núi Chúa National Park (S Vietnam), studying changes in alpha- and beta-diversity across an elevation gradient up to 500 m, encompassing the ecotone between critically endangered lowland dry deciduous forest and mixed evergreen forest at higher elevations. Leaf beetle diversity was assessed using several molecular tree-based species delimitation approaches (with mtDNA cox1 data), species richness using rarefaction and incidence-based diversity indexes, and beta-diversity was investigated decomposing the contribution of species turnover and nestedness. We documented 155 species in the area explored and species-richness estimates 1.5–2.0x higher. Species diversity was similar in both forest types and changes in alpha-diversity along the elevation gradient showed an expected local increase of diversity in the ecotone. Beta-diversity was high among forest paths (average Sørensen's dissimilarity = 0.694) and, tentatively fixing at 300 m the boundary between otherwise continuous biomes, demonstrated similarly high beta-diversity (Sørensen's dissimilarity = 0.581), with samples clustering according to biome/elevation. Highly relevant considering the local scale of the study, beta-diversity had a high contribution of species replacement among locales (54.8%) and between biomes (79.6%), suggesting environmental heterogeneity as the dominant force shaping diversity at such small scale, directly and indirectly on the plant communities. Protection actions in the Park, especially these addressed at the imperative conservation of dry forest, must ponder the small scale at which processes shape species diversity and community structure for inconspicuous, yet extraordinarily diverse organisms such as the leaf beetles. PMID:27276228

Auditory Sensitivity and Masking Profiles for the Sea Otter (Enhydra lutris).

PubMed

Ghoul, Asila; Reichmuth, Colleen

2016-01-01

Sea otters are threatened marine mammals that may be negatively impacted by human-generated coastal noise, yet information about sound reception in this species is surprisingly scarce. We investigated amphibious hearing in sea otters by obtaining the first measurements of absolute sensitivity and critical masking ratios. Auditory thresholds were measured in air and underwater from 0.125 to 40 kHz. Critical ratios derived from aerial masked thresholds from 0.25 to 22.6 kHz were also obtained. These data indicate that although sea otters can detect underwater sounds, their hearing appears to be primarily air adapted and not specialized for detecting signals in background noise.

Epidemic dynamics and endemic states in complex networks

NASA Astrophysics Data System (ADS)

Pastor-Satorras, Romualdo; Vespignani, Alessandro

2001-06-01

We study by analytical methods and large scale simulations a dynamical model for the spreading of epidemics in complex networks. In networks with exponentially bounded connectivity we recover the usual epidemic behavior with a threshold defining a critical point below that the infection prevalence is null. On the contrary, on a wide range of scale-free networks we observe the absence of an epidemic threshold and its associated critical behavior. This implies that scale-free networks are prone to the spreading and the persistence of infections whatever spreading rate the epidemic agents might possess. These results can help understanding computer virus epidemics and other spreading phenomena on communication and social networks.

Critical Deposition Condition of CoNiCrAlY Cold Spray Based on Particle Deformation Behavior

NASA Astrophysics Data System (ADS)

Ichikawa, Yuji; Ogawa, Kazuhiro

2017-02-01

Previous research has demonstrated deposition of MCrAlY coating via the cold spray process; however, the deposition mechanism of cold spraying has not been clearly explained—only empirically described by impact velocity. The purpose of this study was to elucidate the critical deposit condition. Microscale experimental measurements of individual particle deposit dimensions were incorporated with numerical simulation to investigate particle deformation behavior. Dimensional parameters were determined from scanning electron microscopy analysis of focused ion beam-fabricated cross sections of deposited particles to describe the deposition threshold. From Johnson-Cook finite element method simulation results, there is a direct correlation between the dimensional parameters and the impact velocity. Therefore, the critical velocity can describe the deposition threshold. Moreover, the maximum equivalent plastic strain is also strongly dependent on the impact velocity. Thus, the threshold condition required for particle deposition can instead be represented by the equivalent plastic strain of the particle and substrate. For particle-substrate combinations of similar materials, the substrate is more difficult to deform. Thus, this study establishes that the dominant factor of particle deposition in the cold spray process is the maximum equivalent plastic strain of the substrate, which occurs during impact and deformation.

Threshold behaviors of social dynamics and financial outcomes of Ponzi scheme diffusion in complex networks

NASA Astrophysics Data System (ADS)

Fu, Peihua; Zhu, Anding; Ni, He; Zhao, Xin; Li, Xiulin

2018-01-01

Ponzi schemes always lead to mass disasters after collapse. It is important to study the critical behaviors of both social dynamics and financial outcomes for Ponzi scheme diffusion in complex networks. We develop the potential-investor-divestor-investor (PIDI) model by considering the individual behavior of direct reinvestment. We find that only the spreading rate relates to the epidemic outbreak while the reinvestment rate relates to the zero and non-zero final states for social dynamics of both homo- and inhomogeneous networks. Financially, we find that there is a critical spreading threshold, above which the scheme needs not to use its own initial capital for taking off, i.e. the starting cost is covered by the rapidly inflowing funds. However, the higher the cost per recruit, the larger the critical spreading threshold and the worse the financial outcomes. Theoretical and simulation results also reveal that schemes are easier to take off in inhomogeneous networks. The reinvestment rate does not affect the starting. However, it improves the financial outcome in the early stages and postpones the outbreak of financial collapse. Some policy suggestions for the regulator from the perspective of social physics are proposed in the end of the paper.

Effect of a single dose of dextromethorphan on psychomotor performance and working memory capacity.

PubMed

Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Ashor, Ammar Waham

2012-04-01

Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the other half (10 women, 8 men) received dextromethorphan. The choice reaction time, critical flicker fusion threshold, and N-back working memory task were measured before and after 2 h of taking the drugs. Dextromethorphan showed a significant deterioration in the 3-back working memory task (P<0.05). No significant changes were seen as regards the choice reaction time components (total, recognition, motor) and critical flicker fusion threshold (P>0.05). On the other hand, placebo showed no significant changes as regards the choice reaction time, critical flicker fusion threshold, and N-back working memory task (P>0.05). A single dose of dextromethorphan has no effect on attention and arousal but may significantly impair the working memory capacity.

Development of Extended Period Pressure-Dependent Demand Water Distribution Models

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

Judi, David R.; Mcpherson, Timothy N.

2015-03-20

Los Alamos National Laboratory (LANL) has used modeling and simulation of water distribution systems for N-1 contingency analyses to assess criticality of water system assets. Critical components considered in these analyses include pumps, tanks, and supply sources, in addition to critical pipes or aqueducts. A contingency represents the complete removal of the asset from system operation. For each contingency, an extended period simulation (EPS) is run using EPANET. An EPS simulates water system behavior over a time period, typically at least 24 hours. It assesses the ability of a system to respond and recover from asset disruption through distributed storagemore » in tanks throughout the system. Contingencies of concern are identified as those in which some portion of the water system has unmet delivery requirements. A delivery requirement is defined as an aggregation of water demands within a service area, similar to an electric power demand. The metric used to identify areas of unmet delivery requirement in these studies is a pressure threshold of 15 pounds per square inch (psi). This pressure threshold is used because it is below the required pressure for fire protection. Any location in the model with pressure that drops below this threshold at any time during an EPS is considered to have unmet service requirements and is used to determine cascading consequences. The outage area for a contingency is the aggregation of all service areas with a pressure below the threshold at any time during the EPS.« less

Singular Valence Fluctuations at a Kondo Destroyed Quantum Critical Point

NASA Astrophysics Data System (ADS)

Pixley, Jedediah; Kirchner, Stefan; Ingersent, Kevin; Si, Qimiao

2012-02-01

Recent experiments on the heavy fermion superconductor beta-YbAlB4 have indicated that this compound satisfies quantum critical scaling [1]. Motivated by the observation of mixed valency in this material [2], we study the Kondo destruction physics in the mixed-valence regime [3] of a particle-hole asymmetric Anderson impurity model with a pseudogapped density of states. In the vicinity of the quantum critical point we determine the finite temperature spin and charge susceptibilities by utilizing a continuous time quantum Monte Carlo method [4] and the numerical renormalization group. We show that this mixed-valence quantum critical point displays a Kondo breakdown effect. Furthermore, we find that both dynamic spin and charge susceptibilities obey frequency over temperature scaling, and that the static charge susceptibility diverges with a universal exponent. Possible implications of our results for beta-YbAlB4 are discussed. [1] Matsumoto et al, Science 331, 316 (2011). [2] Okawaet al, Physical Review Letters 104, 247201 (2010). [3] J. H. Pixley, S. Kirchner, Kevin Ingersent and Q. Si, arXiv:1108.5227v1 (2011). [4] M. Glossop, S. Kirchner, J. H. Pixley and Q. Si, Phys. Rev. Lett. 107, 076404 (2011).

Evaluation of Maryland abutment scour equation through selected threshold velocity methods

USGS Publications Warehouse

Benedict, S.T.

2010-01-01

The U.S. Geological Survey, in cooperation with the Maryland State Highway Administration, used field measurements of scour to evaluate the sensitivity of the Maryland abutment scour equation to the critical (or threshold) velocity variable. Four selected methods for estimating threshold velocity were applied to the Maryland abutment scour equation, and the predicted scour to the field measurements were compared. Results indicated that performance of the Maryland abutment scour equation was sensitive to the threshold velocity with some threshold velocity methods producing better estimates of predicted scour than did others. In addition, results indicated that regional stream characteristics can affect the performance of the Maryland abutment scour equation with moderate-gradient streams performing differently from low-gradient streams. On the basis of the findings of the investigation, guidance for selecting threshold velocity methods for application to the Maryland abutment scour equation are provided, and limitations are noted.

Mapping Critical Loads of Atmospheric Nitrogen Deposition in the Rocky Mountains, USA

NASA Astrophysics Data System (ADS)

Nanus, L.; Clow, D. W.; Stephens, V. C.; Saros, J. E.

2010-12-01

Atmospheric nitrogen (N) deposition can adversely affect sensitive aquatic ecosystems at high-elevations in the western United States. Critical loads are the amount of deposition of a given pollutant that an ecosystem can receive below which ecological effects are thought not to occur. GIS-based landscape models were used to create maps for high-elevation areas across the Rocky Mountain region showing current atmospheric deposition rates of nitrogen (N), critical loads of N, and exceedances of critical loads of N. Atmospheric N deposition maps for the region were developed at 400 meter resolution using gridded precipitation data and spatially interpolated chemical concentrations in rain and snow. Critical loads maps were developed based on chemical thresholds corresponding to observed ecological effects, and estimated ecosystem sensitivities calculated from basin characteristics. Diatom species assemblages were used as an indicator of ecosystem health to establish critical loads of N. Chemical thresholds (concentrations) were identified for surface waters by using a combination of in-situ growth experiments and observed spatial patterns in surface-water chemistry and diatom species assemblages across an N deposition gradient. Ecosystem sensitivity was estimated using a multiple-linear regression approach in which observed surface water nitrate concentrations at 530 sites were regressed against estimates of inorganic N deposition and basin characteristics (topography, soil type and amount, bedrock geology, vegetation type) to develop predictive models of surface water chemistry. Modeling results indicated that the significant explanatory variables included percent slope, soil permeability, and vegetation type (including barren land, shrub, and grassland) and were used to predict high-elevation surface water nitrate concentrations across the Rocky Mountains. Chemical threshold concentrations were substituted into an inverted form of the model equations and applied to estimate critical loads for each stream reach within a basin, from which critical loads maps were created. Atmospheric N deposition maps were overlaid on the critical loads maps to identify areas in the Rocky Mountain region where critical loads are being exceeded, or where they may do so in the future. This approach may be transferable to other high-elevation areas of the United States and the world.

Percolation critical polynomial as a graph invariant

DOE PAGES

Scullard, Christian R.

2012-10-18

Every lattice for which the bond percolation critical probability can be found exactly possesses a critical polynomial, with the root in [0; 1] providing the threshold. Recent work has demonstrated that this polynomial may be generalized through a definition that can be applied on any periodic lattice. The polynomial depends on the lattice and on its decomposition into identical finite subgraphs, but once these are specified, the polynomial is essentially unique. On lattices for which the exact percolation threshold is unknown, the polynomials provide approximations for the critical probability with the estimates appearing to converge to the exact answer withmore » increasing subgraph size. In this paper, I show how the critical polynomial can be viewed as a graph invariant like the Tutte polynomial. In particular, the critical polynomial is computed on a finite graph and may be found using the deletion-contraction algorithm. This allows calculation on a computer, and I present such results for the kagome lattice using subgraphs of up to 36 bonds. For one of these, I find the prediction p c = 0:52440572:::, which differs from the numerical value, p c = 0:52440503(5), by only 6:9 X 10 -7.« less

Legislating thresholds for drug trafficking: a policy development case study from New South Wales, Australia.

PubMed

Hughes, Caitlin Elizabeth; Ritter, Alison; Cowdery, Nicholas

2014-09-01

Legal thresholds are used in many parts of the world to define the quantity of illicit drugs over which possession is deemed "trafficking" as opposed to "possession for personal use". There is limited knowledge about why or how such laws were developed. In this study we analyse the policy processes underpinning the introduction and expansion of the drug trafficking legal threshold system in New South Wales (NSW), Australia. A critical legal and historical analysis was undertaken sourcing data from legislation, Parliamentary Hansard debates, government inquiries, police reports and research. A timeline of policy developments was constructed from 1970 until 2013 outlining key steps including threshold introduction (1970), expansion (1985), and wholesale revision (1988). We then critically analysed the drivers of each step and the roles played by formal policy actors, public opinion, research/data and the drug trafficking problem. We find evidence that while justified as a necessary tool for effective law enforcement of drug trafficking, their introduction largely preceded overt police calls for reform or actual increases in drug trafficking. Moreover, while the expansion from one to four thresholds had the intent of differentiating small from large scale traffickers, the quantities employed were based on government assumptions which led to "manifest problems" and the revision in 1988 of over 100 different quantities. Despite the revisions, there has remained no further formal review and new quantities for "legal highs" continue to be added based on assumption and an uncertain evidence-base. The development of legal thresholds for drug trafficking in NSW has been arbitrary and messy. That the arbitrariness persists from 1970 until the present day makes it hard to conclude the thresholds have been well designed. Our narrative provides a platform for future policy reform. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Anastasiou, Charalampos; Duhr, Claude; Dulat, Falko

In this study, we compute the gluon fusion Higgs boson cross-section at N 3LO through the second term in the threshold expansion. This calculation constitutes a major milestone towards the full N 3LO cross section. Our result has the best formal accuracy in the threshold expansion currently available, and includes contributions from collinear regions besides subleading corrections from soft and hard regions, as well as certain logarithmically enhanced contributions for general kinematics. We use our results to perform a critical appraisal of the validity of the threshold approximation at N 3LO in perturbative QCD.

Dynamic Regulation of Tgf-B Signaling by Tif1γ: A Computational Approach

PubMed Central

Andrieux, Geoffroy; Fattet, Laurent; Le Borgne, Michel; Rimokh, Ruth; Théret, Nathalie

2012-01-01

TIF1γ (Transcriptional Intermediary Factor 1 γ) has been implicated in Smad-dependent signaling by Transforming Growth Factor beta (TGF-β). Paradoxically, TIF1γ functions both as a transcriptional repressor or as an alternative transcription factor that promotes TGF-β signaling. Using ordinary differential-equation models, we have investigated the effect of TIF1γ on the dynamics of TGF-β signaling. An integrative model that includes the formation of transient TIF1γ-Smad2-Smad4 ternary complexes is the only one that can account for TGF-β signaling compatible with the different observations reported for TIF1γ. In addition, our model predicts that varying TIF1γ/Smad4 ratios play a critical role in the modulation of the transcriptional signal induced by TGF-β, especially for short stimulation times that mediate higher threshold responses. Chromatin immunoprecipitation analyses and quantification of the expression of TGF-β target genes as a function TIF1γ/Smad4 ratios fully validate this hypothesis. Our integrative model, which successfully unifies the seemingly opposite roles of TIF1γ, also reveals how changing TIF1γ/Smad4 ratios affect the cellular response to stimulation by TGF-β, accounting for a highly graded determination of cell fate. PMID:22461896

Reference guide to odor thresholds for hazardous air pollutants listed in the Clean Air Act amendments of 1990

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

Cain, W.S.; Shoaf, C.R.; Velasquez, S.F.

1992-03-01

In response to numerous requests for information related to odor thresholds, this document was prepared by the Air Risk Information Support Center in its role in providing technical assistance to State and Local government agencies on risk assessment of air pollutants. A discussion of basic concepts related to olfactory function and the measurement of odor thresholds is presented. A detailed discussion of criteria which are used to evaluate the quality of published odor threshold values is provided. The use of odor threshold information in risk assessment is discussed. The results of a literature search and review of odor threshold informationmore » for the chemicals listed as hazardous air pollutants in the Clean Air Act amendments of 1990 is presented. The published odor threshold values are critically evaluated based on the criteria discussed and the values of acceptable quality are used to determine a geometric mean or best estimate.« less

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold.

PubMed

Marsden, Kurt C; Jain, Roshan A; Wolman, Marc A; Echeverry, Fabio A; Nelson, Jessica C; Hayer, Katharina E; Miltenberg, Ben; Pereda, Alberto E; Granato, Michael

2018-04-17

Sensory experiences dynamically modify whether animals respond to a given stimulus, but it is unclear how innate behavioral thresholds are established. Here, we identify molecular and circuit-level mechanisms underlying the innate threshold of the zebrafish startle response. From a forward genetic screen, we isolated five mutant lines with reduced innate startle thresholds. Using whole-genome sequencing, we identify the causative mutation for one line to be in the fragile X mental retardation protein (FMRP)-interacting protein cyfip2. We show that cyfip2 acts independently of FMRP and that reactivation of cyfip2 restores the baseline threshold after phenotype onset. Finally, we show that cyfip2 regulates the innate startle threshold by reducing neural activity in a small group of excitatory hindbrain interneurons. Thus, we identify a selective set of genes critical to establishing an innate behavioral threshold and uncover a circuit-level role for cyfip2 in this process. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Development of Simultaneous Beta-and-Coincidence-Gamma Imager for Plant Imaging Research

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

Tai, Yuan-Chuan

2016-09-30

The goal of this project is to develop a novel imaging system that can simultaneously acquire beta and coincidence gamma images of positron sources in thin objects such as leaves of plants. This hybrid imager can be used to measure carbon assimilation in plants quantitatively and in real-time after C-11 labeled carbon-dioxide is administered. A better understanding of carbon assimilation, particularly under the increasingly elevated atmospheric CO 2 level, is extremely critical for plant scientists who study food crop and biofuel production. Phase 1 of this project is focused on the technology development with 3 specific aims: (1) develop amore » hybrid detector that can detect beta and gamma rays simultaneously; (2) develop an imaging system that can differentiate these two types of radiation and acquire beta and coincidence gamma images in real-time; (3) develop techniques to quantify radiotracer distribution using beta and gamma images. Phase 2 of this project is to apply technologies developed in phase 1 to study plants using positron-emitting radionuclide such as 11C to study carbon assimilation in biofuel plants.« less

Analyzing threshold pressure limitations in microfluidic transistors for self-regulated microfluidic circuits

PubMed Central

Kim, Sung-Jin; Yokokawa, Ryuji; Takayama, Shuichi

2012-01-01

This paper reveals a critical limitation in the electro-hydraulic analogy between a microfluidic membrane-valve (μMV) and an electronic transistor. Unlike typical transistors that have similar on and off threshold voltages, in hydraulic μMVs, the threshold pressures for opening and closing are significantly different and can change, even for the same μMVs depending on overall circuit design and operation conditions. We explain, in particular, how the negative values of the closing threshold pressures significantly constrain operation of even simple hydraulic μMV circuits such as autonomously switching two-valve microfluidic oscillators. These understandings have significant implications in designing self-regulated microfluidic devices. PMID:23284181

Picosecond Electric-Field-Induced Threshold Switching in Phase-Change Materials.

PubMed

Zalden, Peter; Shu, Michael J; Chen, Frank; Wu, Xiaoxi; Zhu, Yi; Wen, Haidan; Johnston, Scott; Shen, Zhi-Xun; Landreman, Patrick; Brongersma, Mark; Fong, Scott W; Wong, H-S Philip; Sher, Meng-Ju; Jost, Peter; Kaes, Matthias; Salinga, Martin; von Hoegen, Alexander; Wuttig, Matthias; Lindenberg, Aaron M

2016-08-05

Many chalcogenide glasses undergo a breakdown in electronic resistance above a critical field strength. Known as threshold switching, this mechanism enables field-induced crystallization in emerging phase-change memory. Purely electronic as well as crystal nucleation assisted models have been employed to explain the electronic breakdown. Here, picosecond electric pulses are used to excite amorphous Ag_{4}In_{3}Sb_{67}Te_{26}. Field-dependent reversible changes in conductivity and pulse-driven crystallization are observed. The present results show that threshold switching can take place within the electric pulse on subpicosecond time scales-faster than crystals can nucleate. This supports purely electronic models of threshold switching and reveals potential applications as an ultrafast electronic switch.

Methodological Challenges in Researching Threshold Concepts: A Comparative Analysis of Three Projects

ERIC Educational Resources Information Center

Quinlan, K. M.; Male, S.; Baillie, C.; Stamboulis, A.; Fill, J.; Jaffer, Z.

2013-01-01

Threshold concepts were introduced nearly 10 years ago by Ray Land and Jan Meyer. This work has spawned four international conferences and hundreds of papers. Although the idea has clearly gained traction in higher education, this sub-field does not yet have a fully fledged research methodology or a strong critical discourse about methodology.…

CCAAT-binding factor regulates expression of the beta1 subunit of soluble guanylyl cyclase gene in the BE2 human neuroblastoma cell line

NASA Technical Reports Server (NTRS)

Sharina, Iraida G.; Martin, Emil; Thomas, Anthony; Uray, Karen L.; Murad, Ferid

2003-01-01

Soluble guanylyl cyclase (sGC) is a cytosolic enzyme producing the intracellular messenger cyclic guanosine monophosphate (cGMP) on activation with nitric oxide (NO). sGC is an obligatory heterodimer composed of alpha and beta subunits. We investigated human beta1 sGC transcriptional regulation in BE2 human neuroblastoma cells. The 5' upstream region of the beta1 sGC gene was isolated and analyzed for promoter activity by using luciferase reporter constructs. The transcriptional start site of the beta1 sGC gene in BE2 cells was identified. The functional significance of consensus transcriptional factor binding sites proximal to the transcriptional start site was investigated by site deletions in the 800-bp promoter fragment. The elimination of CCAAT-binding factor (CBF) and growth factor independence 1 (GFI1) binding cores significantly diminished whereas deletion of the NF1 core elevated the transcription. Electrophoretic mobility-shift assay (EMSA) and Western analysis of proteins bound to biotinated EMSA probes confirmed the interaction of GFI1, CBF, and NF1 factors with the beta1 sGC promoter. Treatment of BE2 cells with genistein, known to inhibit the CBF binding to DNA, significantly reduced protein levels of beta1 sGC by inhibiting transcription. In summary, our study represents an analysis of the human beta1 sGC promoter regulation in human neuroblastoma BE2 cells and identifies CBF as a critically important factor in beta1 sGC expression.

A Novel Di-Leucine Motif at the N-Terminus of Human Organic Solute Transporter Beta Is Essential for Protein Association and Membrane Localization.

PubMed

Xu, Shuhua; Soroka, Carol J; Sun, An-Qiang; Backos, Donald S; Mennone, Albert; Suchy, Frederick J; Boyer, James L

2016-01-01

The heteromeric membrane protein Organic Solute Transporter alpha/beta is the major bile acid efflux transporter in the intestine. Physical association of its alpha and beta subunits is essential for their polarized basolateral membrane localization and function in the transport of bile acids and other organic solutes. We identified a highly conserved acidic dileucine motif (-EL20L21EE) at the extracellular amino-tail of organic solute transporter beta from multiple species. To characterize the role of this protein interacting domain in the association of the human beta and alpha subunits and in membrane localization of the transporter, Leu20 and Leu21 on the amino-tail of human organic solute transporter beta were replaced with alanines by site-directed mutagenesis. Co-immunoprecipitation study in HEK293 cells demonstrated that substitution of the leucine residues with alanines prevented the interaction of the human beta mutant with the alpha subunit. Membrane biotinylation demonstrated that the LL/AA mutant eliminated membrane expression of both subunits. Computational-based modelling of human organic solute transporter beta suggested that the LL/AA mutation substantially alters both the structure and lipophilicity of the surface, thereby not only affecting the interaction with the alpha subunit but also possibly impacting the capacity of the beta subunit to traffick through the cell and interact with the membrane. In summary, our findings indicate that the dileucine motif in the extracellular N-terminal region of human organic solute transporter beta subunit plays a critical role in the association with the alpha subunit and in its polarized plasma membrane localization.

Dissecting the role of matrix metalloproteinases (MMP) and integrin alpha(v)beta3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-Type 1-MMP and alpha(v)beta3 are critical.

PubMed

Nisato, Riccardo E; Hosseini, Ghamartaj; Sirrenberg, Christian; Butler, Georgina S; Crabbe, Thomas; Docherty, Andrew J P; Wiesner, Matthias; Murphy, Gillian; Overall, Christopher M; Goodman, Simon L; Pepper, Michael S

2005-10-15

Matrix metalloproteinase (MMP)-2 and its hemopexin C domain autolytic fragment (also called PEX) have been proposed to be crucial for angiogenesis. Here, we have investigated the dependency of in vitro angiogenesis on MMP-mediated extracellular proteolysis and integrin alpha(v)beta3-mediated cell adhesion in a three-dimensional collagen I model. The hydroxamate-based synthetic inhibitors BB94, CT1399, and CT1847 inhibited endothelial cell invasion, as did neutralizing anti-membrane-type 1-MMP (MT1-MMP) antibodies and tissue inhibitor of MMP (TIMP)-2 and TIMP-3 but not TIMP-1. This confirmed the pivotal importance of MT1-MMP over other MMPs in this model. Invasion was also inhibited by a nonpeptidic antagonist of integrin alpha(v)beta3, EMD 361276. Although PEX strongly inhibited pro-MMP-2 activation, when contaminating lipopolysaccharide was neutralized, PEX neither affected angiogenesis nor bound integrin alpha(v)beta(3). Moreover, no specific binding of pro-MMP-2 to integrin alpha(v)beta3 was found, whereas only one out of four independently prepared enzymatically active MMP-2 preparations could bind integrin alpha(v)beta3 , and this in a PEX-independent manner. Likewise, integrin alpha(v)beta3 -expressing cells did not bind MMP-2-coated surfaces. Hence, these findings show that endothelial cell invasion of collagen I gels is MT1-MMP and alpha(v)beta3 - dependent but MMP-2 independent and does not support a role for PEX in alpha(v)beta3 integrin binding or in modulating angiogenesis in this system.

Role of caspase-1 and interleukin-1{beta} in acetaminophen-induced hepatic inflammation and liver injury

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

Williams, C. David; Farhood, Anwar; Jaeschke, Hartmut, E-mail: hjaeschke@kumc.ed

2010-09-15

Acetaminophen (APAP) overdose can result in serious liver injury and potentially death. Toxicity is dependent on metabolism of APAP to a reactive metabolite initiating a cascade of intracellular events resulting in hepatocellular necrosis. This early injury triggers a sterile inflammatory response with formation of cytokines and innate immune cell infiltration in the liver. Recently, IL-1{beta} signaling has been implicated in the potentiation of APAP-induced liver injury. To test if IL-1{beta} formation through caspase-1 is critical for the pathophysiology, C57Bl/6 mice were treated with the pan-caspase inhibitor Z-VD-fmk to block the inflammasome-mediated maturation of IL-1{beta} during APAP overdose (300 mg/kg APAP).more » This intervention did not affect IL-1{beta} gene transcription but prevented the increase in IL-1{beta} plasma levels. However, APAP-induced liver injury and neutrophil infiltration were not affected. Similarly, liver injury and the hepatic neutrophilic inflammation were not attenuated in IL-1-receptor-1 deficient mice compared to wild-type animals. To evaluate the potential of IL-1{beta} to increase injury, mice were given pharmacological doses of IL-1{beta} after APAP overdose. Despite increased systemic activation of neutrophils and recruitment into the liver, there was no alteration in injury. We conclude that endogenous IL-1{beta} formation after APAP overdose is insufficient to activate and recruit neutrophils into the liver or cause liver injury. Even high pharmacological doses of IL-1{beta}, which induce hepatic neutrophil accumulation and activation, do not enhance APAP-induced liver injury. Thus, IL-1 signaling is irrelevant for APAP hepatotoxicity. The inflammatory cascade is a less important therapeutic target than intracellular signaling pathways to attenuate APAP-induced liver injury.« less

Opposite Smad and chicken ovalbumin upstream promoter transcription factor inputs in the regulation of the collagen VII gene promoter by transforming growth factor-beta.

PubMed

Calonge, María Julia; Seoane, Joan; Massagué, Joan

2004-05-28

A critical component of the epidermal basement membrane, collagen type VII, is produced by keratinocytes and fibroblasts, and its production is stimulated by the cytokine transforming growth factor-beta (TGF-beta). The gene, COL7A1, is activated by TGF-beta via Smad transcription factors in cooperation with AP1. Here we report a previously unsuspected level of complexity in this regulatory process. We provide evidence that TGF-beta may activate the COL7A1 promoter by two distinct inputs operating through a common region of the promoter. One input is provided by TGF-beta-induced Smad complexes via two Smad binding elements that function redundantly depending on the cell type. The second input is provided by relieving the COL7A1 promoter from chicken ovalbumin upstream promoter transcription factor (COUP-TF)-mediated transcriptional repression. We identified COUP-TFI and -TFII as factors that bind to the TGF-beta-responsive region of the COL7A1 promoter in an expression library screening. COUP-TFs bind to a site between the two Smad binding elements independently of Smad or AP1 and repress the basal and TGF-beta-stimulated activities of this promoter. We provide evidence that endogenous COUP-TF activity represses the COL7A1 promoter. Furthermore, we show that TGF-beta addition causes a rapid and profound down-regulation of COUP-TF expression in keratinocytes and fibroblasts. The results suggest that TGF-beta signaling may exert tight control over COL7A1 by offsetting the balance between opposing Smad and COUP-TFs.

Opposite beta2-glycoprotein I requirement for the binding of infectious and autoimmune antiphospholipid antibodies to cardiolipin liposomes is associated with antibody avidity.

PubMed

Celli, C M; Gharavi, A E; Chaimovich, H

1999-01-12

The aim of this study was to investigate the interaction of antiphospholipid antibodies (aPL) from two different populations (patients with autoimmune or infectious disorders) with cardiolipin (CL) arranged in a defined bilayer. beta2-Glycoprotein I (beta2GPI), an apolipoprotein that plays a critical role in the aPL binding to phospholipids, was quantified by dot blot in purified IgG-aPL samples, further classified according to apparent avidity to CL. In solid-phase assays, beta2GPI increased, preferentially, the binding of low-avidity autoimmune aPL to CL but inhibited the binding of low-avidity syphilitic aPL. In the absence of beta2GPI, both autoimmune and infectious aPL induced the leakage of the entrapped fluorescent probe, carboxyfluorescein (CF), from small unilamellar vesicles containing CL. aPL-induced probe leakage was protein concentration-dependent and characterized by a lag-phase onset of 100-120 min. beta2GPI increased the leakage rate induced by low-avidity autoimmune aPL only and inhibited the leakage induced by all syphilitic aPL. The following conclusions were provided: (1) in the absence of beta2GPI, autoimmune and infectious aPL bind to CL in a bilayer, inducing liposome leakage; (2) the leakage mechanism induced by aPL is suggested to be intravesicular; (3) beta2GPI requirement for phospholipid binding in both solid and fluid phase is associated to aPL avidity; (4) CL alone or the CL-beta2GPI complex are the most likely epitopes for autoimmune aPL; (5) aPL from syphilis patients can only form the CL-aPL complex, supporting that beta2GPI is not (part of) the target epitope.

THE SPATIO-TEMPORAL EVOLUTION OF SOLAR FLARES OBSERVED WITH AIA/SDO: FRACTAL DIFFUSION, SUB-DIFFUSION, OR LOGISTIC GROWTH?

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

Aschwanden, Markus J., E-mail: aschwanden@lmsal.com

2012-09-20

We explore the spatio-temporal evolution of solar flares by fitting a radial expansion model r(t) that consists of an exponentially growing acceleration phase, followed by a deceleration phase that is parameterized by the generalized diffusion function r(t){proportional_to}{kappa}(t - t{sub 1}){sup {beta}/2}, which includes the logistic growth limit ({beta} = 0), sub-diffusion ({beta} = 0-1), classical diffusion ({beta} = 1), super-diffusion ({beta} = 1-2), and the linear expansion limit ({beta} = 2). We analyze all M- and X-class flares observed with Geostationary Operational Environmental Satellite and Atmospheric Imaging Assembly/Solar Dynamics Observatory (SDO) during the first two years of the SDO mission,more » amounting to 155 events. We find that most flares operate in the sub-diffusive regime ({beta} = 0.53 {+-} 0.27), which we interpret in terms of anisotropic chain reactions of intermittent magnetic reconnection episodes in a low plasma-{beta} corona. We find a mean propagation speed of v = 15 {+-} 12 km s{sup -1}, with maximum speeds of v{sub max} = 80 {+-} 85 km s{sup -1} per flare, which is substantially slower than the sonic speeds expected for thermal diffusion of flare plasmas. The diffusive characteristics established here (for the first time for solar flares) is consistent with the fractal-diffusive self-organized criticality model, which predicted diffusive transport merely based on cellular automaton simulations.« less

Role of the nitric oxide/cyclic GMP/Ca2+ signaling pathway in the pyrogenic effect of interleukin-1beta.

PubMed

Palmi, Mitri; Meini, Antonella

2002-04-01

Interleukin-1beta (IL-1beta) has a wide spectrum of inflammatory, metabolic, haemopoietic, and immunological properties. Because it produces fever when injected into animals and humans, it is considered an endogenous pyrogen. There is evidence to suggest that Ca2+ plays a critical role in the central mechanisms of thermoregulation, and in the intracellular signaling pathways controlling fever induced by IL-1beta and other pyrogens. Data from different labs indicate that Ca2+ and Na+ determine the temperature set point in the posterior hypothalamus (PH) of various mammals and that changes in Ca2+ and PGE2 concentrations in the cerebrospinal fluid (CSF) of these animals are associated with IL-1beta-induced fever. Antipyretic drugs such as acetylsalicylic acid, dexamethasone, and lipocortin 5-(204-212) peptide counteract IL-1beta-induced fever and abolish changes in Ca2+ and PGE2 concentrations in CSF. In vitro studies have established that activation of the nitric oxide (NO)/cyclic GMP (cGMP) pathway is part of the signaling cascade transducing Ca2+ mobilization in response to IL-1beta and that the ryanodine (RY)- and inositol-(1,4,5)-trisphosphate (IP3)-sensitive pools are the main source of the mobilized Ca2+. It is concluded that the NO/cGMP/Ca2+ pathway is part of the signaling cascade subserving some of the multiple functions of IL-1beta.

MAdCAM-1 expressing sacral lymph node in the lymphotoxin beta-deficient mouse provides a site for immune generation following vaginal herpes simplex virus-2 infection.

PubMed

Soderberg, Kelly A; Linehan, Melissa M; Ruddle, Nancy H; Iwasaki, Akiko

2004-08-01

The members of the lymphotoxin (LT) family of molecules play a critical role in lymphoid organogenesis. Whereas LT alpha-deficient mice lack all lymph nodes and Peyer's patches, mice deficient in LT beta retain mesenteric lymph nodes and cervical lymph nodes, suggesting that an LT beta-independent pathway exists for the generation of mucosal lymph nodes. In this study, we describe the presence of a lymph node in LT beta-deficient mice responsible for draining the genital mucosa. In the majority of LT beta-deficient mice, a lymph node was found near the iliac artery, slightly misplaced from the site of the sacral lymph node in wild-type mice. The sacral lymph node of the LT beta-deficient mice, as well as that of the wild-type mice, expressed the mucosal addressin cell adhesion molecule-1 similar to the mesenteric lymph node. Following intravaginal infection with HSV type 2, activated dendritic cells capable of stimulating a Th1 response were found in this sacral lymph node. Furthermore, normal HSV-2-specific IgG responses were generated in the LT beta-deficient mice following intravaginal HSV-2 infection even in the absence of the spleen. Therefore, an LT beta-independent pathway exists for the development of a lymph node associated with the genital mucosa, and such a lymph node serves to generate potent immune responses against viral challenge.

Regional rainfall thresholds for landslide occurrence using a centenary database

NASA Astrophysics Data System (ADS)

Vaz, Teresa; Luís Zêzere, José; Pereira, Susana; Cruz Oliveira, Sérgio; Garcia, Ricardo A. C.; Quaresma, Ivânia

2018-04-01

This work proposes a comprehensive method to assess rainfall thresholds for landslide initiation using a centenary landslide database associated with a single centenary daily rainfall data set. The method is applied to the Lisbon region and includes the rainfall return period analysis that was used to identify the critical rainfall combination (cumulated rainfall duration) related to each landslide event. The spatial representativeness of the reference rain gauge is evaluated and the rainfall thresholds are assessed and calibrated using the receiver operating characteristic (ROC) metrics. Results show that landslide events located up to 10 km from the rain gauge can be used to calculate the rainfall thresholds in the study area; however, these thresholds may be used with acceptable confidence up to 50 km from the rain gauge. The rainfall thresholds obtained using linear and potential regression perform well in ROC metrics. However, the intermediate thresholds based on the probability of landslide events established in the zone between the lower-limit threshold and the upper-limit threshold are much more informative as they indicate the probability of landslide event occurrence given rainfall exceeding the threshold. This information can be easily included in landslide early warning systems, especially when combined with the probability of rainfall above each threshold.

Early continuous white noise exposure alters l-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit glutamate receptor 2 and gamma-aminobutyric acid type a receptor subunit beta3 protein expression in rat auditory cortex.

PubMed

Xu, Jinghong; Yu, Liping; Zhang, Jiping; Cai, Rui; Sun, Xinde

2010-02-15

Auditory experience during the postnatal critical period is essential for the normal maturation of auditory function. Previous studies have shown that rearing infant rat pups under conditions of continuous moderate-level noise delayed the emergence of adult-like topographic representational order and the refinement of response selectivity in the primary auditory cortex (A1) beyond normal developmental benchmarks and indefinitely blocked the closure of a brief, critical-period window. To gain insight into the molecular mechanisms of these physiological changes after noise rearing, we studied expression of the AMPA receptor subunit GluR2 and GABA(A) receptor subunit beta3 in the auditory cortex after noise rearing. Our results show that continuous moderate-level noise rearing during the early stages of development decreases the expression levels of GluR2 and GABA(A)beta3. Furthermore, noise rearing also induced a significant decrease in the level of GABA(A) receptors relative to AMPA receptors. However, in adult rats, noise rearing did not have significant effects on GluR2 and GABA(A)beta3 expression or the ratio between the two units. These changes could have a role in the cellular mechanisms involved in the delayed maturation of auditory receptive field structure and topographic organization of A1 after noise rearing. Copyright 2009 Wiley-Liss, Inc.

Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

PubMed

Chevalier, Julie; Chamoux, Catherine; Hammès, Florence; Chicoye, Annie

2016-01-01

The paper aimed to estimate the incremental cost-effectiveness ratio (ICER) at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015. The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS) 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results. From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a) 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod) were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY) of 0.281, corresponding to an ICER of €13,110/QALY. Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells.

PubMed

Belkin, A M; Zhidkova, N I; Balzac, F; Altruda, F; Tomatis, D; Maier, A; Tarone, G; Koteliansky, V E; Burridge, K

1996-01-01

The cytoplasmic domains of integrins provide attachment of these extracellular matrix receptors to the cytoskeleton and play a critical role in integrin-mediated signal transduction. In this report we describe the identification, expression, localization, and initial functional characterization of a novel form of beta 1 integrin, termed beta 1D. This isoform contains a unique alternatively spliced cytoplasmic domain of 50 amino acids, with the last 24 amino acids encoded by an additional exon. Of these 24 amino acids, 11 are conserved when compared to the beta 1A isoform, but 13 are unique (Zhidkova, N. I., A. M. Belkin, and R. Mayne. 1995. Biochem. Biophys. Res. Commun. 214:279-285; van der Flier, A., I. Kuikman, C. Baudoin, R, van der Neuf, and A. Sonnenberg. 1995. FEBS Lett. 369:340-344). Using an anti-peptide antibody against the beta 1D integrin subunit, we demonstrated that the beta 1D isoform is synthesized only in skeletal and cardiac muscles, while very low amounts of beta 1A were detected by immunoblot in striated muscles. Whereas beta 1A could not be detected in adult skeletal muscle fibers and cardiomyocytes by immunofluorescence, beta 1D was localized to the sarcolemma of both cell types. In skeletal muscle, beta 1D was concentrated in costameres, myotendinous, and neuromuscular junctions. In cardiac muscle this beta 1 isoform was found in costamers and intercalated discs. beta 1D was associated with alpha 7A and alpha 7B in adult skeletal muscle. In cardiomyocytes of adult heart, alpha 7B was the major partner for the beta 1D isoform. beta 1D could not be detected in proliferating C2C12 myoblasts, but it appeared immediately after myoblast fusion and its amount continued to rise during myotube growth and maturation. In contrast, expression of the beta 1A isoform was downregulated during myodifferentiation in culture and it was completely displaced by beta 1D in mature differentiated myotubes. We also analyzed some functional properties of the beta 1D integrin subunit. Expression of human beta 1D in CHO cells led to its localization at focal adhesions. Clustering of this integrin isoform on the cell surface stimulated tyrosine phosphorylation of pp125FAK (focal adhesion kinase) and caused transient activation of mitogen-activated protein (MAP) kinases. These data indicate that beta 1D and beta 1A integrin isoforms are functionally similar with regard to integrin-mediated signaling.

Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain.

PubMed

Lautenbacher, Stefan; Kunz, Miriam; Strate, Peter; Nielsen, Jesper; Arendt-Nielsen, Lars

2005-06-01

Experimental data on age-related changes in pain perception have so far been contradictory. It has appeared that the type of pain induction method is critical in this context, with sensitivity to heat pain being decreased whereas sensitivity to pressure pain may be even enhanced in the elderly. Furthermore, it has been shown that temporal summation of heat pain is more pronounced in the elderly but it has remained unclear whether age differences in temporal summation are also evident when using other pain induction methods. No studies on age-related changes in spatial summation of pain have so far been conducted. The aim of the present study was to provide a comprehensive survey on age-related changes in pain perception, i.e. in somatosensory thresholds (warmth, cold, vibration), pain thresholds (heat, pressure) and spatial and temporal summation of heat and pressure pain. We investigated 20 young (mean age 27.1 years) and 20 elderly (mean age 71.6 years) subjects. Our results confirmed and extended previous findings by showing that somatosensory thresholds for non-noxious stimuli increase with age whereas pressure pain thresholds decrease and heat pain thresholds show no age-related changes. Apart from an enhanced temporal summation of heat pain, pain summation was not found to be critically affected by age. The results of the present study provide evidence for stimulus-specific changes in pain perception in the elderly, with deep tissue (muscle) nociception being affected differently by age than superficial tissue (skin) nociception. Summation mechanisms contribute only moderately to age changes in pain perception.

Economics, socio-ecological resilience and ecosystem services.

PubMed

Farley, Joshua; Voinov, Alexey

2016-12-01

The economic process transforms raw materials and energy into economic products and waste. On a finite planet, continued economic growth threatens to surpass critical socio-ecological thresholds and undermine ecosystem services upon which humans and all other species depend. For most systems, whether such thresholds exist, where they lie and whether they are reversible cannot be known with certainty until they are crossed. We argue that our central economic challenge is to maintain the resilience of the current socio-ecological regime. We must reduce net impacts of economic activity to avoid critical ecological thresholds while ensuring economic necessities. Conventional economists pursue continuous growth as the central goal of economic activity, and assume that the price mechanism and technological breakthroughs ensure system resilience. Unfortunately, the price mechanism fails to address ecological thresholds because it ignores unowned ecosystem services, and fails to address economic thresholds because it ignores the needs of the poorest individuals, who live on the edge of them. Panarchy theory suggests that systems go through a cycle of growth, conservation, release and renewal. Managing a subsystem too long for growth or conservation-which many consider to be the goal of sustainability-actually threatens to collapse the higher-level system upon which that subsystem depends. Black Swan theory suggests we should seek to reduce the risk of catastrophic thresholds and promote the likelihood of technological breakthroughs. Economic degrowth, or planned release, is required to avoid catastrophic collapse. At the same time, publicly funded, open source information can help stimulate the technological breakthroughs economists count on to ensure resilience. Copyright © 2016. Published by Elsevier Ltd.

In vivo relevance of two critical levels for NAD(P)H:quinone oxidoreductase (NQO1)-mediated cellular protection against electrophile toxicity found in vitro.

PubMed

de Haan, Laura H J; Pot, Gerda K; Aarts, Jac M M J G; Rietjens, Ivonne M C M; Alink, Gerrit M

2006-08-01

NAD(P)H:quinone oxidoreductase (NQO1)-mediated detoxification of quinones is suggested to be involved in cancer prevention. In the present study, using transfected CHO cells, it was demonstrated that the relation between NQO1 activity and the resulting protection against the cytotoxicity of menadione shows a steep dose-response curve revealing a 'lower protection threshold' of 0.5mumol DCPIP/min/mg protein and an 'upper protection threshold' at 1mumol DCPIP/min/mg protein. In an additional in vivo experiment it was investigated how both in vitro critical activity levels of NQO1, relate to NQO1 activities in mice and man, either without or upon induction of the enzyme by butylated hydroxyanisol (BHA) or indole-3-carbinol (I(3)C). Data from an experiment with CD1 mice revealed that base-line NQO1 levels in liver, kidney, small intestine, colon and lung are generally below the observed 'lower protection threshold' in vitro, this also holds for most human tissue S-9 samples. To achieve NQO1 levels above this 'lower protection threshold' will require 5-20 fold NQO1 induction. Discussion focuses on the relevance of the in vitro NQO1 activity thresholds for the in vivo situation. We conclude that increased protection against menadione toxicity can probably not be achieved by NQO1 induction but should be achieved by other mechanisms. Whether this conclusion also holds for other electrophiles and the in vivo situation awaits further definition of their NQO1 protection thresholds.

Effects of cytokines on the pituitary-adrenal axis in cancer patients.

PubMed

Nolten, W E; Goldstein, D; Lindstrom, M; McKenna, M V; Carlson, I H; Trump, D L; Schiller, J; Borden, E C; Ehrlich, E N

1993-10-01

Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-beta (IFN-beta ser), 90 or 450 x 10(6) IU, IFN-gamma, 0.1-100 x 10(6) IU, or TNF 125-275 micrograms/m2. Sixty to 120 min after IFN-beta ser injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-beta ser administration. IFN-gamma > or = 30 x 10(6) IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

Electrorotation of novel electroactive polymer composites in uniform DC and AC electric fields

NASA Astrophysics Data System (ADS)

Zrinyi, Miklós; Nakano, Masami; Tsujita, Teppei

2012-06-01

Novel electroactive polymer composites have been developed that could spin in uniform DC and AC electric fields. The angular displacement as well as rotation of polymer disks around an axis that is perpendicular to the direction of the applied electric field was studied. It was found that the dynamics of the polymer rotor is very complex. Depending on the strength of the static DC field, three regimes have been observed: no rotation occurs below a critical threshold field intensity, oscillatory motion takes place just above this value and continuous rotation can be observed above the critical threshold field intensity. It was also found that low frequency AC fields could also induce angular deformation.

Methods for forewarning of critical condition changes in monitoring civil structures

DOEpatents

Abercrombie, Robert K.; Hively, Lee M.

2013-04-02

Sensor modules (12) including accelerometers (20) are placed on a physical structure (10) and tri-axial accelerometer data is converted to mechanical power (P) data (41) which then processed to provide a forewarning (57) of a critical event concerning the physical structure (10). The forewarning is based on a number of occurrences of a composite measure of dissimilarity (C.sub.i) exceeding a forewarning threshold over a defined sampling time; and a forewarning signal (58) is provided to a human observer through a visual, audible or tangible signal. A forewarning of a structural failure can also be provided based on a number of occurrences of (C.sub.i) above a failure value threshold.

Global threshold dynamics of an SIVS model with waning vaccine-induced immunity and nonlinear incidence.

PubMed

Yang, Junyuan; Martcheva, Maia; Wang, Lin

2015-10-01

Vaccination is the most effective method of preventing the spread of infectious diseases. For many diseases, vaccine-induced immunity is not life long and the duration of immunity is not always fixed. In this paper, we propose an SIVS model taking the waning of vaccine-induced immunity and general nonlinear incidence into consideration. Our analysis shows that the model exhibits global threshold dynamics in the sense that if the basic reproduction number is less than 1, then the disease-free equilibrium is globally asymptotically stable implying the disease dies out; while if the basic reproduction number is larger than 1, then the endemic equilibrium is globally asymptotically stable indicating that the disease persists. This global threshold result indicates that if the vaccination coverage rate is below a critical value, then the disease always persists and only if the vaccination coverage rate is above the critical value, the disease can be eradicated. Copyright © 2015 Elsevier Inc. All rights reserved.

Epidemic Model with Isolation in Multilayer Networks

NASA Astrophysics Data System (ADS)

Zuzek, L. G. Alvarez; Stanley, H. E.; Braunstein, L. A.

2015-07-01

The Susceptible-Infected-Recovered (SIR) model has successfully mimicked the propagation of such airborne diseases as influenza A (H1N1). Although the SIR model has recently been studied in a multilayer networks configuration, in almost all the research the isolation of infected individuals is disregarded. Hence we focus our study in an epidemic model in a two-layer network, and we use an isolation parameter w to measure the effect of quarantining infected individuals from both layers during an isolation period tw. We call this process the Susceptible-Infected-Isolated-Recovered (SIIR) model. Using the framework of link percolation we find that isolation increases the critical epidemic threshold of the disease because the time in which infection can spread is reduced. In this scenario we find that this threshold increases with w and tw. When the isolation period is maximum there is a critical threshold for w above which the disease never becomes an epidemic. We simulate the process and find an excellent agreement with the theoretical results.

The critical density for star formation in HII galaxies

NASA Technical Reports Server (NTRS)

Taylor, Christopher L.; Brinks, Elias; Skillman, Evan D.

1993-01-01

The star formation rate (SFR) in galaxies is believed to obey a power law relation with local gas density, first proposed by Schmidt (1959). Kennicutt (1989) has shown that there is a threshold density above which star formation occurs, and for densities at or near the threshold density, the DFR is highly non-linear, leading to bursts of star formation. Skillman (1987) empirically determined this threshold for dwarf galaxies to be approximately 1 x 10(exp 21) cm(exp -2), at a linear resolution of 500pc. During the course of our survey for HI companion clouds to HII galaxies, we obtained high resolution HI observations of five nearby HII galaxies. HII galaxies are low surface brightness, rich in HI, and contain one or a few high surface brightness knots whose optical spectra resemble those of HII regions. These knots are currently experiencing a burst of star formation. After Kennicutt (1989) we determine the critical density for star formation in the galaxies, and compare the predictions with radio and optical data.

Humans and seasonal climate variability threaten large-bodied coral reef fish with small ranges

PubMed Central

Mellin, C.; Mouillot, D.; Kulbicki, M.; McClanahan, T. R.; Vigliola, L.; Bradshaw, C. J. A.; Brainard, R. E.; Chabanet, P.; Edgar, G. J.; Fordham, D. A.; Friedlander, A. M.; Parravicini, V.; Sequeira, A. M. M.; Stuart-Smith, R. D.; Wantiez, L.; Caley, M. J.

2016-01-01

Coral reefs are among the most species-rich and threatened ecosystems on Earth, yet the extent to which human stressors determine species occurrences, compared with biogeography or environmental conditions, remains largely unknown. With ever-increasing human-mediated disturbances on these ecosystems, an important question is not only how many species can inhabit local communities, but also which biological traits determine species that can persist (or not) above particular disturbance thresholds. Here we show that human pressure and seasonal climate variability are disproportionately and negatively associated with the occurrence of large-bodied and geographically small-ranging fishes within local coral reef communities. These species are 67% less likely to occur where human impact and temperature seasonality exceed critical thresholds, such as in the marine biodiversity hotspot: the Coral Triangle. Our results identify the most sensitive species and critical thresholds of human and climatic stressors, providing opportunity for targeted conservation intervention to prevent local extinctions. PMID:26839155

Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics.

PubMed

Mohd Hafiz, Abdul-Aziz; Staatz, C E; Kirkpatrick, C M J; Lipman, J; Roberts, J A

2012-01-01

Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant antibiotic concentrations rather than high peak concentrations are most likely to result in effective treatment of infections caused by susceptible bacteria. Continuous administration has been suggested as an alternative strategy, to conventional intermittent dosing, to optimise beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of emerging data, we elected to systematically investigate the published literature describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics administered by continuous or intermittent infusion. We found that the studies have been performed in various patient populations including critically ill, cancer and cystic fibrosis patients. Available in vitro PK/PD data conclusively support the administration of beta-lactams via continuous infusion for maximizing bacterial killing from consistent attainment of pharmacodynamic end-points. In addition, clinical outcome data supports equivalence, even with the use of a lower dose by continuous infusion. However, the present clinical data is limited with small sample sizes common with insufficient power to detect advantages in favour of either dosing strategy. With abundant positive pre-clinical data as well as document in vivo PK/PD advantages, large multi-centre trials are needed to describe whether continuous administration of beta-lactams is truly more effective than intermittent dosing.

Patterns of taxonomic, phylogenetic diversity during a long-term succession of forest on the Loess Plateau, China: insights into assembly process

PubMed Central

Chai, Yongfu; Yue, Ming; Liu, Xiao; Guo, Yaoxin; Wang, Mao; Xu, Jinshi; Zhang, Chenguang; Chen, Yu; Zhang, Lixia; Zhang, Ruichang

2016-01-01

Quantifying the drivers underlying the distribution of biodiversity during succession is a critical issue in ecology and conservation, and also can provide insights into the mechanisms of community assembly. Ninety plots were established in the Loess Plateau region of northern Shaanxi in China. The taxonomic and phylogenetic (alpha and beta) diversity were quantified within six succession stages. Null models were used to test whether phylogenetic distance observed differed from random expectations. Taxonomic beta diversity did not show a regular pattern, while phylogenetic beta diversity decreased throughout succession. The shrub stage occurred as a transition from phylogenetic overdispersion to clustering either for NRI (Net Relatedness Index) or betaNRI. The betaNTI (Nearest Taxon Index) values for early stages were on average phylogenetically random, but for the betaNRI analyses, these stages were phylogenetically overdispersed. Assembly of woody plants differed from that of herbaceous plants during late community succession. We suggest that deterministic and stochastic processes respectively play a role in different aspects of community phylogenetic structure for early succession stage, and that community composition of late succession stage is governed by a deterministic process. In conclusion, the long-lasting evolutionary imprints on the present-day composition of communities arrayed along the succession gradient. PMID:27272407

Patterns of taxonomic, phylogenetic diversity during a long-term succession of forest on the Loess Plateau, China: insights into assembly process.

PubMed

Chai, Yongfu; Yue, Ming; Liu, Xiao; Guo, Yaoxin; Wang, Mao; Xu, Jinshi; Zhang, Chenguang; Chen, Yu; Zhang, Lixia; Zhang, Ruichang

2016-06-08

Quantifying the drivers underlying the distribution of biodiversity during succession is a critical issue in ecology and conservation, and also can provide insights into the mechanisms of community assembly. Ninety plots were established in the Loess Plateau region of northern Shaanxi in China. The taxonomic and phylogenetic (alpha and beta) diversity were quantified within six succession stages. Null models were used to test whether phylogenetic distance observed differed from random expectations. Taxonomic beta diversity did not show a regular pattern, while phylogenetic beta diversity decreased throughout succession. The shrub stage occurred as a transition from phylogenetic overdispersion to clustering either for NRI (Net Relatedness Index) or betaNRI. The betaNTI (Nearest Taxon Index) values for early stages were on average phylogenetically random, but for the betaNRI analyses, these stages were phylogenetically overdispersed. Assembly of woody plants differed from that of herbaceous plants during late community succession. We suggest that deterministic and stochastic processes respectively play a role in different aspects of community phylogenetic structure for early succession stage, and that community composition of late succession stage is governed by a deterministic process. In conclusion, the long-lasting evolutionary imprints on the present-day composition of communities arrayed along the succession gradient.

Mediation of wound-related Rous sarcoma virus tumorigenesis by TFG (transforming growth factor)-. beta

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

Sieweke, M.H.; Bissell, M.J.; Thompson, N.L.

1990-06-29

In Rous sarcoma virus (RSV)-infected chickens, wounding leads to tumor formation with nearly 100% frequency in tissues that would otherwise remain tumor-free. Identifying molecular mediators of this phenomenon should yield important clues to the mechanisms involved in RSV tumorigenesis. Immunohistochemical staining showed that TGF-{beta} is present locally shortly after wounding, but not in unwounded controls. In addition, subcutaneous administration of recombinant transforming growth factor {beta}1 (TGF-{beta}1) could substitute completely for wounding in tumor induction. A treatment protocol of four doses of 800 nanograms of TGF-{beta} resulted in v-src-expressing tumors with 100% frequency; four doses of only 10 nanograms still ledmore » to tumor formation in 80% of the animals. This effect was specific, as other growth factors with suggested roles in would healing did not elicit the same response. Epidermal growth factor (EGF) or TGF-{alpha} had no effect, and platelet-derived growth factor (PDGF) or insulin-like growth factor-1 (IGF-1) yielded only occasional tumors after longer latency. TGF-{beta} release during the would-healing response may thus be a critical event that creates a conducive environment for RSV tumorigenesis and may act as a cofactor for transformation in this system. 31 refs., 3 figs., 2 tabs.« less

Partial regeneration of beta-cells in the islets of Langerhans by Nymphayol a sterol isolated from Nymphaea stellata (Willd.) flowers.

PubMed

Subash-Babu, P; Ignacimuthu, S; Agastian, P; Varghese, Babu

2009-04-01

Reduction of the beta-cell mass is critical in the pathogenesis of diabetes mellitus. The discovery of agents which induce regeneration of pancreatic beta-cells would be useful to develop new therapeutic approaches to treat diabetes. The present study was aimed at identifying a new agent for the control of diabetes through regeneration of pancreatic beta cells and insulin secretory potential. Nymphaea stellata flower chloroform extract (NSFCExt) showed significant plasma glucose lowering effect. Further NSFCExt was utilized to isolate and identify the lead compound based on bioassay guided fractionation; we found Nymphayol (25,26-dinorcholest-5-en-3beta-ol) a new crystal [space group P2(1) (No. 4), a=9.618(5), b=7.518(5), c=37.491(5)]. It was purified by repeat column. The structure was determined on the basis of X-ray crystallography and spectral data. Oral administration of Nymphayol for 45 days significantly (p<0.05) lowered the blood glucose level and more importantly it effectively increased the insulin content in diabetic rats. In addition, Nymphayol increased the number of beta cell mass enormously. Islet-like cell clusters in the islets of Langerhans were clearly observed based on histochemical and immunohistochemical study.

Activation of PKC{beta}{sub II} and PKC{theta} is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation

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

Heo, Kyung-Sun; Department of Pharmacy, Chungnam National University, Yuseong, Daejeon; Kim, Dong-Uk

Native LDL may be a mitogenic stimulus of VSMC proliferation in lesions where endothelial disruption occurs. Recent studies have demonstrated that the mitogenic effects of LDL are accompanied by Erk1/2 activation via an unknown G-protein-coupled receptor (GPCR). In this article, we report that LDL translocated PKC{beta}{sub II} and PKC{theta} from cytosol to plasma membrane, and inhibition of PKC{beta}{sub II} and PKC{theta} decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKC{beta}{sub II} and PKC{theta}, suggesting that Gi protein plays a role in LDL effects. Of LPA, S1P, andmore » LDL, whose signaling is conveyed via Gi/o proteins, only LDL induced translocation of PKC{beta}{sub II} and PKC{theta}. Inhibition of PKC{beta}{sub II} or PKC{theta}, as well as of Erk1/2 and GPCR, decreases LDL-induced upregulation of Egr-1, which is critical for cell proliferation. This is the first report, to our knowledge, that the participation of PKC{theta} in VSMC proliferation is unique.« less

Temporal context processing within hippocampal subfields.

PubMed

Wang, Fang; Diana, Rachel A

2016-07-01

The episodic memory system can differentiate similar events based on the temporal information associated with the events. Temporal context, which is at least partially determined by the events that precede or follow the critical event, may be a cue to differentiate events. The purpose of the present study is to investigate whether the hippocampal dentate gyrus (DG)/CA3 and CA1 subfields are sensitive to changes in temporal context and, if so, whether the subregions show a linear or threshold-like response to similar temporal contexts. Participants incidentally encoded a series of object picture triplets and 20 of them were included in final analyses. The third picture in each triplet was operationally defined as the target and the first two pictures served as temporal context for the target picture. Each target picture was presented twice with temporal context manipulated to be either repeated, high similarity, low similarity, or new on the second presentation. We extracted beta parameters for the repeated target as a function of the type of temporal context. We expected to see repetition suppression, a reduction in the beta values, in response to repetition of the target. If temporal context information is included in the representation of the target within a given region, this repetition suppression should be greater for target images that were preceded by their original context than for target images preceded by a new context. Neuroimaging results showed that CA1, but not DG/CA3, modifies the target's representation based on its temporal context. Right CA1 did not distinguish high similarity temporal context from repeated context but did distinguish low similarity temporal context from repeated context. These results indicate that CA1 is sensitive to temporal context and suggest that it does not differentiate between a substantially similar temporal context and an identical temporal context. In contrast, DG/CA3 does not appear to process temporal context as defined in the current experiment. Copyright © 2016 Elsevier Inc. All rights reserved.

Nitrogen Critical Loads for an Alpine Meadow Ecosystem on the Tibetan Plateau.

PubMed

Zong, Ning; Shi, Peili; Song, Minghua; Zhang, Xianzhou; Jiang, Jing; Chai, Xi

2016-03-01

Increasing atmospheric nitrogen (N) deposition has the potential to alter plant diversity and thus the function and stability of terrestrial ecosystems. N-limited alpine ecosystems are expected to be particularly susceptible to increasing N deposition. However, little is known about the critical loads and saturation thresholds of ecosystem responses to increasing N deposition on the Tibetan Plateau, despite its importance to ecosystem management. To evaluate the N critical loads and N saturation thresholds in an alpine ecosystem, in 2010, we treated an alpine meadow with five levels of N addition (0, 10, 20, 40, and 80 kg N ha(-1) year(-1)) and characterized plant and soil responses. The results showed that plant species richness and diversity index did not statistically vary with N addition treatments, but they both changed with years. N addition affected plant cover and aboveground productivity, especially for grasses, and soil chemical features. The N critical loads and saturation thresholds, in terms of plant cover and biomass change at the community level, were 8.8-12.7 and 50 kg N ha(-1) year(-1) (including the ambient N deposition rate), respectively. However, pronounced changes in soil inorganic N and net N mineralization occurred under the 20 and 40 kg N ha(-1) year(-1) treatments. Our results indicate that plant community cover and biomass are more sensitive than soil to increasing N inputs. The plant community composition in alpine ecosystems on the Qinghai-Tibetan Plateau may change under increasing N deposition in the future.

Is the Critical Shields Stress for Incipient Sediment Motion Dependent on Bed Slope in Natural Channels? No.

NASA Astrophysics Data System (ADS)

Phillips, C. B.; Jerolmack, D. J.

2017-12-01

Understanding when coarse sediment begins to move in a river is essential for linking rivers to the evolution of mountainous landscapes. Unfortunately, the threshold of surface particle motion is notoriously difficult to measure in the field. However, recent studies have shown that the threshold of surface motion is empirically correlated with channel slope, a property that is easy to measure and readily available from the literature. These studies have thoroughly examined the mechanistic underpinnings behind the observed correlation and produced suitably complex models. These models are difficult to implement for natural rivers using widely available data, and thus others have treated the empirical regression between slope and the threshold of motion as a predictive model. We note that none of the authors of the original studies exploring this correlation suggested their empirical regressions be used in a predictive fashion, nevertheless these regressions between slope and the threshold of motion have found their way into numerous recent studies engendering potentially spurious conclusions. We demonstrate that there are two significant problems with using these empirical equations for prediction: (1) the empirical regressions are based on a limited sampling of the phase space of bed-load rivers and (2) the empirical measurements of bankfull and critical shear stresses are paired. The upshot of these problems limits the empirical relations predictive capacity to field sites drawn from the same region of the bed-load river phase space and that the paired nature of the data introduces a spurious correlation when considering the ratio of bankfull to critical shear stress. Using a large compilation of bed-load river hydraulic geometry data, we demonstrate that the variation within independently measured values of the threshold of motion changes systematically with bankfull shields stress and not channel slope. Additionally, we highlight using several recent datasets the potential pitfalls that one can encounter when using simplistic empirical regressions to predict the threshold of motion showing that while these concerns could be construed as subtle the resulting implications can be substantial.

Basic Diagnosis and Prediction of Persistent Contrail Occurrence using High-resolution Numerical Weather Analyses/Forecasts and Logistic Regression. Part I: Effects of Random Error

NASA Technical Reports Server (NTRS)

Duda, David P.; Minnis, Patrick

2009-01-01

Straightforward application of the Schmidt-Appleman contrail formation criteria to diagnose persistent contrail occurrence from numerical weather prediction data is hindered by significant bias errors in the upper tropospheric humidity. Logistic models of contrail occurrence have been proposed to overcome this problem, but basic questions remain about how random measurement error may affect their accuracy. A set of 5000 synthetic contrail observations is created to study the effects of random error in these probabilistic models. The simulated observations are based on distributions of temperature, humidity, and vertical velocity derived from Advanced Regional Prediction System (ARPS) weather analyses. The logistic models created from the simulated observations were evaluated using two common statistical measures of model accuracy, the percent correct (PC) and the Hanssen-Kuipers discriminant (HKD). To convert the probabilistic results of the logistic models into a dichotomous yes/no choice suitable for the statistical measures, two critical probability thresholds are considered. The HKD scores are higher when the climatological frequency of contrail occurrence is used as the critical threshold, while the PC scores are higher when the critical probability threshold is 0.5. For both thresholds, typical random errors in temperature, relative humidity, and vertical velocity are found to be small enough to allow for accurate logistic models of contrail occurrence. The accuracy of the models developed from synthetic data is over 85 percent for both the prediction of contrail occurrence and non-occurrence, although in practice, larger errors would be anticipated.

The importance of reference materials in doping-control analysis.

PubMed

Mackay, Lindsey G; Kazlauskas, Rymantas

2011-08-01

Currently a large range of pure substance reference materials are available for calibration of doping-control methods. These materials enable traceability to the International System of Units (SI) for the results generated by World Anti-Doping Agency (WADA)-accredited laboratories. Only a small number of prohibited substances have threshold limits for which quantification is highly important. For these analytes only the highest quality reference materials that are available should be used. Many prohibited substances have no threshold limits and reference materials provide essential identity confirmation. For these reference materials the correct identity is critical and the methods used to assess identity in these cases should be critically evaluated. There is still a lack of certified matrix reference materials to support many aspects of doping analysis. However, in key areas a range of urine matrix materials have been produced for substances with threshold limits, for example 19-norandrosterone and testosterone/epitestosterone (T/E) ratio. These matrix-certified reference materials (CRMs) are an excellent independent means of checking method recovery and bias and will typically be used in method validation and then regularly as quality-control checks. They can be particularly important in the analysis of samples close to threshold limits, in which measurement accuracy becomes critical. Some reference materials for isotope ratio mass spectrometry (IRMS) analysis are available and a matrix material certified for steroid delta values is currently under production. In other new areas, for example the Athlete Biological Passport, peptide hormone testing, designer steroids, and gene doping, reference material needs still need to be thoroughly assessed and prioritised.

[Effect of beta-ecdysterone in competitive cultures of Drosophila melanogaster].

PubMed

Botella, L M; Ménsua, J L

1987-03-01

High levels of beta-ecdysterone (more than 1 microgram/ml) have been shown to decrease larva-adult viability and to speed up developmental times when supplied to the media in crowding cultures. The highest doses (100 micrograms/ml) of ecdysterone suppresses almost completely the phenomenon of larval stop in the third instar of development, first reported by our laboratory in overcrowded situations. Thus, one may deduce that stopped larvae could have low levels of ecdysone, and perhaps these are the ultimate physiological cause of their arrested development before the critical larva-pupa molt.

Low energy analysis techniques for CUORE

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

Alduino, C.; Alfonso, K.; Artusa, D. R.

CUORE is a tonne-scale cryogenic detector operating at the Laboratori Nazionali del Gran Sasso (LNGS) that uses tellurium dioxide bolometers to search for neutrinoless double-beta decay of 130Te. CUORE is also suitable to search for low energy rare events such as solar axions or WIMP scattering, thanks to its ultra-low background and large target mass. However, to conduct such sensitive searches requires improving the energy threshold to 10 keV. Here in this article, we describe the analysis techniques developed for the low energy analysis of CUORE-like detectors, using the data acquired from November 2013 to March 2015 by CUORE-0, amore » single-tower prototype designed to validate the assembly procedure and new cleaning techniques of CUORE. We explain the energy threshold optimization, continuous monitoring of the trigger efficiency, data and event selection, and energy calibration at low energies in detail. We also present the low energy background spectrum of CUORE-0 below 60keV. Finally, we report the sensitivity of CUORE to WIMP annual modulation using the CUORE-0 energy threshold and background, as well as an estimate of the uncertainty on the nuclear quenching factor from nuclear recoils inCUORE-0.« less

Low energy analysis techniques for CUORE

DOE PAGES

Alduino, C.; Alfonso, K.; Artusa, D. R.; ...

2017-12-12

CUORE is a tonne-scale cryogenic detector operating at the Laboratori Nazionali del Gran Sasso (LNGS) that uses tellurium dioxide bolometers to search for neutrinoless double-beta decay of 130Te. CUORE is also suitable to search for low energy rare events such as solar axions or WIMP scattering, thanks to its ultra-low background and large target mass. However, to conduct such sensitive searches requires improving the energy threshold to 10 keV. Here in this article, we describe the analysis techniques developed for the low energy analysis of CUORE-like detectors, using the data acquired from November 2013 to March 2015 by CUORE-0, amore » single-tower prototype designed to validate the assembly procedure and new cleaning techniques of CUORE. We explain the energy threshold optimization, continuous monitoring of the trigger efficiency, data and event selection, and energy calibration at low energies in detail. We also present the low energy background spectrum of CUORE-0 below 60keV. Finally, we report the sensitivity of CUORE to WIMP annual modulation using the CUORE-0 energy threshold and background, as well as an estimate of the uncertainty on the nuclear quenching factor from nuclear recoils inCUORE-0.« less

The Area Coverage of Geophysical Fields as a Function of Sensor Field-of View

NASA Technical Reports Server (NTRS)

Key, Jeffrey R.

1994-01-01

In many remote sensing studies of geophysical fields such as clouds, land cover, or sea ice characteristics, the fractional area coverage of the field in an image is estimated as the proportion of pixels that have the characteristic of interest (i.e., are part of the field) as determined by some thresholding operation. The effect of sensor field-of-view on this estimate is examined by modeling the unknown distribution of subpixel area fraction with the beta distribution, whose two parameters depend upon the true fractional area coverage, the pixel size, and the spatial structure of the geophysical field. Since it is often not possible to relate digital number, reflectance, or temperature to subpixel area fraction, the statistical models described are used to determine the effect of pixel size and thresholding operations on the estimate of area fraction for hypothetical geophysical fields. Examples are given for simulated cumuliform clouds and linear openings in sea ice, whose spatial structures are described by an exponential autocovariance function. It is shown that the rate and direction of change in total area fraction with changing pixel size depends on the true area fraction, the spatial structure, and the thresholding operation used.

Masked hearing thresholds of a beluga whale ( Delphinapterus leucas) in icebreaker noise

NASA Astrophysics Data System (ADS)

Erbe, C.; Farmer, D. M.

An experiment is presented that measured masked hearing thresholds of a beluga whale at the Vancouver Aquarium. The masked signal was a typical beluga vocalization; the masking noise included two types of icebreaker noise and naturally occurring icecracking noise. Thresholds were measured behaviorally in a go/no-go paradigm. Results were that bubbler system noise exhibited the strongest masking effect with a critical noise-to-signal ratio of 15.4 dB. Propeller cavitation noise completely masked the vocalization for noise-to-signal ratios greater than 18.0 dB. Natural icecracking noise showed the least interference with a threshold at 29.0 dB. A psychophysical analysis indicated that the whale did not have a consistent decision bias.

Dynamic Sensor Tasking for Space Situational Awareness via Reinforcement Learning

NASA Astrophysics Data System (ADS)

Linares, R.; Furfaro, R.

2016-09-01

This paper studies the Sensor Management (SM) problem for optical Space Object (SO) tracking. The tasking problem is formulated as a Markov Decision Process (MDP) and solved using Reinforcement Learning (RL). The RL problem is solved using the actor-critic policy gradient approach. The actor provides a policy which is random over actions and given by a parametric probability density function (pdf). The critic evaluates the policy by calculating the estimated total reward or the value function for the problem. The parameters of the policy action pdf are optimized using gradients with respect to the reward function. Both the critic and the actor are modeled using deep neural networks (multi-layer neural networks). The policy neural network takes the current state as input and outputs probabilities for each possible action. This policy is random, and can be evaluated by sampling random actions using the probabilities determined by the policy neural network's outputs. The critic approximates the total reward using a neural network. The estimated total reward is used to approximate the gradient of the policy network with respect to the network parameters. This approach is used to find the non-myopic optimal policy for tasking optical sensors to estimate SO orbits. The reward function is based on reducing the uncertainty for the overall catalog to below a user specified uncertainty threshold. This work uses a 30 km total position error for the uncertainty threshold. This work provides the RL method with a negative reward as long as any SO has a total position error above the uncertainty threshold. This penalizes policies that take longer to achieve the desired accuracy. A positive reward is provided when all SOs are below the catalog uncertainty threshold. An optimal policy is sought that takes actions to achieve the desired catalog uncertainty in minimum time. This work trains the policy in simulation by letting it task a single sensor to "learn" from its performance. The proposed approach for the SM problem is tested in simulation and good performance is found using the actor-critic policy gradient method.

Determination of a Critical Sea Ice Thickness Threshold for the Central Arctic Ocean

NASA Astrophysics Data System (ADS)

Ford, V.; Frauenfeld, O. W.; Nowotarski, C. J.

2017-12-01

While sea ice extent is readily measurable from satellite observations and can be used to assess the overall survivability of the Arctic sea ice pack, determining the spatial variability of sea ice thickness remains a challenge. Turbulent and conductive heat fluxes are extremely sensitive to ice thickness but are dominated by the sensible heat flux, with energy exchange expected to increase with thinner ice cover. Fluxes over open water are strongest and have the greatest influence on the atmosphere, while fluxes over thick sea ice are minimal as heat conduction from the ocean through thick ice cannot reach the atmosphere. We know that turbulent energy fluxes are strongest over open ocean, but is there a "critical thickness of ice" where fluxes are considered non-negligible? Through polar-optimized Weather Research and Forecasting model simulations, this study assesses how the wintertime Arctic surface boundary layer, via sensible heat flux exchange and surface air temperature, responds to sea ice thinning. The region immediately north of Franz Josef Land is characterized by a thickness gradient where sea ice transitions from the thickest multi-year ice to the very thin marginal ice seas. This provides an ideal location to simulate how the diminishing Arctic sea ice interacts with a warming atmosphere. Scenarios include both fixed sea surface temperature domains for idealized thickness variability, and fixed ice fields to detect changes in the ocean-ice-atmosphere energy exchange. Results indicate that a critical thickness threshold exists below 1 meter. The threshold is between 0.4-1 meters thinner than the critical thickness for melt season survival - the difference between first year and multi-year ice. Turbulent heat fluxes and surface air temperature increase as sea ice thickness transitions from perennial ice to seasonal ice. While models predict a sea ice free Arctic at the end of the warm season in future decades, sea ice will continue to transform seasonally during Polar winter. However, despite seasonal sea ice change, if and where its thickness remains below this critical threshold, the Arctic Ocean will continue interacting with the overlying atmosphere and contributing to Arctic amplification during the cold season.

Establishing storm thresholds for the Spanish Gulf of Cádiz coast

NASA Astrophysics Data System (ADS)

Del Río, Laura; Plomaritis, Theocharis A.; Benavente, Javier; Valladares, María; Ribera, Pedro

2012-03-01

In this study critical thresholds are defined for storm impacts along the Spanish coast of the Gulf of Cádiz. The thresholds correspond to the minimum wave and tide conditions necessary to produce significant morphological changes on beaches and dunes and/or damage on coastal infrastructure or human occupation. Threshold definition was performed by computing theoretical sea-level variations during storms and comparing them with the topography of the study area and the location of infrastructure at a local level. Specifically, the elevations of the berm, the dune foot and the entrance of existing washovers were selected as threshold parameters. The total sea-level variation generated by a storm event was estimated as the sum of the tidal level, the wind-induced setup, the barometric setup and the wave-associated sea-level variation (wave setup and runup), assuming a minimum interaction between the different processes. These components were calculated on the basis of parameterisations for significant wave height (Hs) obtained for the oceanographic and environmental conditions of the Gulf of Cadiz. For this purpose real data and reanalysis time-series (HIPOCAS project) were used. Validation of the obtained results was performed for a range of coastal settings over the study area. The obtained thresholds for beach morphological changes in spring tide conditions range between a significant wave height of 1.5 m and 3.7 m depending on beach characteristics, while for dune foot erosion are around 3.3 to 3.7 m and for damage to infrastructure around 7.2 m. In case of neap tide conditions these values are increased on average by 50% over the areas with large tidal range. Furthermore, records of real damage in coastal infrastructure caused by storms were collected at a regional level from newspapers and other bibliographic sources and compared with the hydrodynamic conditions that caused the damage. These were extracted from the hindcast database of the HIPOCAS project, including parameters such as storm duration, mean and maximum wave height and wave direction. Results show that the duration of the storm is not critical in determining the occurrence of coastal damage in the regional study area. This way, the threshold would be defined as a duration ≥30 h, with moderate average wave height (≥3.3 m) and high maximum wave height (≥4.1 m) approaching from the 3rd and 4th quadrants, during mean or spring tide situation. The calculated thresholds constitute snapshots of risk conditions within a certain time framework. Beach and nearshore zones are extremely dynamic, and also the characteristics of occupation on the coast change over time, so critical storm thresholds will change accordingly and therefore will need to be updated.

Removal of Long-Lived Radon Daughters by Electropolishing Thin Layers of Stainless Steel

NASA Astrophysics Data System (ADS)

White, James; Schnee, Richard; Bunker, Raymond; Bowles, Michael; Cushman, Priscilla; Epland, Matthew; Pepin, Mark; Guiseppe, Vince

2012-10-01

Long-lived alpha and beta emitters in the Radon decay chain on detector surfaces may be limiting background in many experiments attempting to detect dark matter or neutrinoless double beta decay. To screen detector surfaces for this radioactive contamination, a low-radiation, multi-wire proportional chamber (the BetaCage) is under construction. Removal of Pb-210 implanted on its 25-micron stainless steel wires without causing significant variation in the diameter of the wires is critical to the BetaCage's ultimate sensitivity. An apparatus to perform electropolishing trials to remove roughly a micron of material has been assembled. These trials have shown promising results. Stainless steel square samples implanted with Pb-210 have shown counts with a reduction factor greater than 10 after electropolishing according to gamma assay. Furthermore, alpha counting has produced similar results, with a reduction factor greater than 100. Lastly, the diameters of wires after electropolishing have remained sufficiently uniform, with reduction in thickness consistent with expectations.

Perpendicular and Parallel Ion Stochastic Heating by Kinetic Alfvén Wave Turbulence in the Solar Wind

NASA Astrophysics Data System (ADS)

Hoppock, I. W.; Chandran, B. D. G.

2017-12-01

The dissipation of turbulence is a prime candidate to explain the heating of collisionless plasmas like the solar wind. We consider the heating of protons and alpha particles using test particle simulations with a broad spectrum of randomly phased kinetic Alfvén waves (KAWs). Previous research extensively simulated and analytically considered stochastic heating at low plasma beta for conditions similar to coronal holes and the near-sun solar wind. We verify the analytical models of proton and alpha particle heating rates, and extend these simulations to plasmas with beta of order unity like in the solar wind at 1 au. Furthermore, we consider cases with very large beta of order 100, relevant to other astrophysical plasmas. We explore the parameter dependency of the critical KAW amplitude that breaks the gyro-center approximation and leads to stochastic gyro-orbits of the particles. Our results suggest that stochastic heating by KAW turbulence is an efficient heating mechanisms for moderate to high beta plasmas.

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

Liebhaber, S.A.; Weiss, I.; Cash, F.E.

Synthesis of normal human hemoglobin A, {alpha}{sub 2}{beta}{sub 2}, is based upon balanced expression of genes in the {alpha}-globin gene cluster on chromosome 15 and the {beta}-globin gene cluster on chromosome 11. Full levels of erythroid-specific activation of the {beta}-globin cluster depend on sequences located at a considerable distance 5{prime} to the {beta}-globin gene, referred to as the locus-activating or dominant control region. The existence of an analogous element(s) upstream of the {alpha}-globin cluster has been suggested from observations on naturally occurring deletions and experimental studies. The authors have identified an individual with {alpha}-thalassemia in whom structurally normal {alpha}-globin genesmore » have been inactivated in cis by a discrete de novo 35-kilobase deletion located {approximately}30 kilobases 5{prime} from the {alpha}-globin gene cluster. They conclude that this deletion inactivates expression of the {alpha}-globin genes by removing one or more of the previously identified upstream regulatory sequences that are critical to expression of the {alpha}-globin genes.« less

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

MOSTELLER, RUSSELL D.

Previous studies have indicated that ENDF/B-VII preliminary releases {beta}-2 and {beta}-3, predecessors to the recent initial release of ENDF/B-VII.0, produce significantly better overall agreement with criticality benchmarks than does ENDF/B-VI. However, one of those studies also suggests that improvements still may be needed for thermal plutonium cross sections. The current study substantiates that concern by examining criticality benchmarks for unreflected spheres of plutonium-nitrate solutions and for slightly and heavily borated mixed-oxide (MOX) lattices. Results are presented for the JEFF-3.1 and JENDL-3.3 nuclear data libraries as well as ENDF/B-VII.0 and ENDF/B-VI. It is shown that ENDF/B-VII.0 tends to overpredict reactivity formore » thermal plutonium benchmarks over at least a portion of the thermal range. In addition, it is found that additional benchmark data are needed for the deep thermal range.« less

Transforming growth factor-β1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts.

PubMed

Jablonska, Ewa; Markart, Philipp; Zakrzewicz, Dariusz; Preissner, Klaus T; Wygrecka, Malgorzata

2010-04-09

Coagulation factor XII (FXII) is a liver-derived serine protease involved in fibrinolysis, coagulation, and inflammation. The regulation of FXII expression is largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that has been linked to several pathological processes, including tissue fibrosis by modulating procoagulant and fibrinolytic activities. This study investigated whether TGF-beta1 may regulate FXII expression in human lung fibroblasts. Treatment of human lung fibroblasts with TGF-beta1 resulted in a time-dependent increase in FXII production, activation of p44/42, p38, JNK, and Akt, and phosphorylation and translocation into the nucleus of Smad3. However, TGF-beta1-induced FXII expression was repressed only by the JNK inhibitor and JNK and Smad3 antisense oligonucleotides but not by MEK, p38, or phosphoinositide 3-kinase blockers. JNK inhibition had no effect on TGF-beta1-induced Smad3 phosphorylation, association with Smad4, and its translocation into the nucleus but strongly suppressed Smad3-DNA complex formation. FXII promoter analysis revealed that the -299/+1 region was sufficient for TGF-beta1 to induce FXII expression. Sequence analysis of this region detected a potential Smad-binding element at position -272/-269 (SBE-(-272/-269)). Chromatin immunoprecipitation and streptavidin pulldown assays demonstrated TGF-beta1-dependent Smad3 binding to SBE-(-272/-269). Mutation or deletion of SBE-(-272/-269) substantially reduced TGF-beta1-mediated activation of the FXII promoter. Clinical relevance was demonstrated by elevated FXII levels and its co-localization with fibroblasts in the lungs of patients with acute respiratory distress syndrome. Our results show that JNK/Smad3 pathway plays a critical role in TGF-beta1-induced FXII expression in human lung fibroblasts and implicate its possible involvement in pathological conditions characterized by elevated TGF-beta1 levels.

Glucocorticoids enhance activation of the human type II 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase gene.

PubMed

Feltus, F Alex; Cote, Stephanie; Simard, Jacques; Gingras, Sebastien; Kovacs, William J; Nicholson, Wendell E; Clark, Barbara J; Melner, Michael H

2002-09-01

Glucocorticoids indirectly alter adrenocortical steroid output through the inhibition of ACTH secretion by the anterior pituitary. However, previous studies suggest that glucocorticoids can directly affect adrenocortical steroid production. Therefore, we have investigated the ability of glucocorticoids to affect transcription of adrenocortical steroid biosynthetic enzymes. One potential target of glucocorticoid action in the adrenal is an enzyme critical for adrenocortical steroid production: 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (3beta-HSD). Treatment of the adrenocortical cell line (H295R) with the glucocorticoid agonist dexamethasone (DEX) increased cortisol production and 3beta-HSD mRNA levels alone or in conjunction with phorbol ester. This increase in 3beta-HSD mRNA was paralleled by increases in Steroidogenic Acute Regulatory Protein (StAR) mRNA levels. The human type II 3beta-HSD promoter lacks a consensus palindromic glucocorticoid response element (GRE) but does contain a Stat5 response element (Stat5RE) suggesting that glucocorticoids could affect type II 3beta-HSD transcription via interaction with Stat5. Transfection experiments show enhancement of human type II 3beta-HSD promoter activity by coexpression of the glucocorticoid receptor (GR) and Stat5A and treatment with 100nM dexamethasone. Furthermore, removal of the Stat5RE either by truncation of the 5' flanking sequence in the promoter or introduction of point mutations to the Stat5RE abolished the ability of DEX to enhance 3beta-HSD promoter activity. These studies demonstrate the ability of glucocorticoids to directly enhance the expression of an adrenal steroidogenic enzyme gene albeit independent of a consensus palindromic glucocorticoid response element.

14-3-3 sigma and 14-3-3 zeta plays an opposite role in cell growth inhibition mediated by transforming growth factor-beta 1.

PubMed

Hong, Hye-Young; Jeon, Woo-Kwang; Bae, Eun-Jin; Kim, Shin-Tae; Lee, Ho-Jae; Kim, Seong-Jin; Kim, Byung-Chul

2010-03-01

The expression of 14-3-3 proteins is dysregulated in various types of cancer. This study was undertaken to investigate the effects of 14-3-3 zeta and 14-3-3 sigma on cell growth inhibition mediated by transforming growth factor-beta 1 (TGF-beta1). Mouse mammary epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-beta1-mediated growth inhibition displayed increased expression of 14-3-3 zeta and decreased expression of 14-3-3 sigma compared with parental Eph4 cells. Using small interfering RNA-mediated knockdown and overexpression of 14-3-3 sigma or 14-3-3 zeta, we showed that 14-3-3 sigma is required for TGF-beta1-mediated growth inhibition whereas 14-3-3 zeta negatively modulates this growth inhibitory response. Notably, overexpression of 14-3-3 zeta increased the level of Smad3 protein that is phosphorylated at linker regions and cannot mediate the TGF-beta1 growth inhibitory response. Consistent with this finding, mutation of the 14-3-3 zeta phosphorylation sites in Smad3 markedly reduced the 14-3-3 zeta-mediated inhibition of TGF-beta1-induced p15 promoter-reporter activity and cell cycle arrest, suggesting that these residues are critical targets of 14-3-3 zeta in the suppression of TGF-beta1-mediated growth. Taken together, our findings indicate that dysregulation of 14-3-3 sigma or 14-3-3 zeta contributes to TGF-beta1 resistance in cancer cells.

Alterations induced by E-cadherin and beta-catenin antibodies during the development of Bufo arenarum (Anura-Bufonidae).

PubMed

Izaguirre, M F; Adur, J F; Soler, A P; Casco, V H

2001-10-01

E(epithelial)-cadherin is a member of a calcium-dependent family of cell surface glycoproteins involved in cell-cell adhesion and morphogenesis. Catenins are a large family of proteins that connect the cadherins to the cytoskeleton. They are important for cadherin function and for transducing signals involved in specification of cell fate during embryogenesis. The best characterized catenins include alpha-, beta-, gamma-, and p120-catenin. Using specific antibodies, we studied the expression and distribution of E-cadherin, and alpha- and beta-catenin in developmental stages of Bufo arenarum toad. The three proteins were found co-localized in stages 19 to 41 of development. Surprisingly, E-cadherin was the only of these three proteins found earlier than stage 19. To test whether E-cadherin and beta-catenin have a functional role in Bufo arenarum embryogenesis, stage 17 whole embryos were incubated with anti-E-cadherin and beta-catenin antibodies. Both anti-E-cadherin and anti-beta-catenin antibodies induced severe morphological alterations. However, while alterations produced by the anti-beta-catenin antibody, showed some variability from the most severe (neural tube and notochord duplication) to a simple delay in development, the alterations with anti-E-cadherin were homogeneous. These observations suggest a critical role for E-cadherin and beta-catenin in the early embryonic development of the Bufo arenarum toad. Our results are consistent with the developmental role of these proteins in other species. One of the most surprising findings was the blockage with the anti-beta-catenin antibodies on later embryo stages, and we hypothesize that the partial axes duplication could be mediated by the notochord induction.

A novel mechanism by which hepatocyte growth factor blocks tubular epithelial to mesenchymal transition.

PubMed

Yang, Junwei; Dai, Chunsun; Liu, Youhua

2005-01-01

Hepatocyte growth factor (HGF) is a potent antifibrotic cytokine that blocks tubular epithelial to mesenchymal transition (EMT) induced by TGF-beta1. However, the underlying mechanism remains largely unknown. This study investigated the signaling events that lead to HGF blockade of the TGF-beta1-initiated EMT. Incubation of human kidney epithelial cells HKC with HGF only marginally affected the expression of TGF-beta1 and its type I and type II receptors, suggesting that disruption of TGF-beta1 signaling likely plays a critical role in mediating HGF inhibition of TGF-beta1 action. However, HGF neither affected TGF-beta1-induced Smad-2 phosphorylation and its subsequent nuclear translocation nor influenced the expression of inhibitory Smad-6 and -7 in tubular epithelial cells. HGF specifically induced the expression of Smad transcriptional co-repressor SnoN but not Ski and TG-interacting factor at both mRNA and protein levels in HKC cells. SnoN physically interacted with activated Smad-2 by forming transcriptionally inactive complex and overrode the profibrotic action of TGF-beta1. In vivo, HGF did not affect Smad-2 activation and its nuclear accumulation in tubular epithelium, but it restored SnoN protein abundance in the fibrotic kidney in obstructive nephropathy. Hence, HGF blocks EMT by antagonizing TGF-beta1's action via upregulating Smad transcriptional co-repressor SnoN expression. These findings not only identify a novel mode of interaction between the signals activated by HGF receptor tyrosine kinase and TGF-beta receptor serine/threonine kinases but also illustrate the feasibility of confining Smad activity as an effective strategy for blocking renal fibrosis.

Viability of bifidobacteria strains in yogurt with added oat beta-glucan and corn starch during cold storage.

PubMed

Rosburg, Valerie; Boylston, Terri; White, Pamela

2010-06-01

Probiotics must be consumed at a level of 10(7) CFU/mL for successful colonization of the gut. In yogurts containing beneficial cultures, the survival of probiotic strains can quickly decline below this critical concentration during cold storage. We hypothesized that beta-glucan would increase the viability of bifidobacteria strains in yogurt during cold storage. Yogurts were produced containing 0.44% beta-glucan (concentrated or freeze-dried) extracted from whole oat flour and/or 1.33% modified corn starch, and bifidobacteria (B. breve or B. longum) at a concentration of at least 10(9) CFU/mL. All yogurts were stored at 4 degrees C. Bifidobacteria and yogurt cultures, Streptococcus thermophilus and Lactobacillus delbureckii subsp. bulgaricus, were enumerated from undisturbed aliquots before fermentation, after fermentation, and once a week for 5 wk. S. thermophilus and L. bulgaricus maintained a concentration of at least 10(8) CFU/mL in yogurts containing concentrated or freeze-dried beta-glucan regardless of starch addition, and in the control with no added beta-glucan or starch. Similarly, the probiotic, Bifidobacterium breve, survived above a therapeutic level in all treatments. The addition of beta-glucan prolonged the survival of Bifidobacterium longum at a concentration of at least 10(7) CFU/mL by up to 2 wk on average beyond the control. Further, the inclusion of concentrated beta-glucan in yogurt improved survival of B. longum above 10(7) CFU/mL by 1 wk longer than did freeze-dried beta-glucan. Study results suggest that beta-glucan has a protective effect on bifidobacteria in yogurt when stressed by low-temperature storage.

Freezing cytorrhysis and critical temperature thresholds for photosystem II in the peat moss Sphagnum capillifolium.

PubMed

Buchner, Othmar; Neuner, Gilbert

2010-07-01

Leaflets of Sphagnum capillifolium were exposed to temperatures from -5 degrees C to +60 degrees C under controlled conditions while mounted on a microscope stage. The resultant cytological response to these temperature treatments was successfully monitored using a light and fluorescence microscope. In addition to the observable cytological changes during freezing cytorrhysis and heat exposure on the leaflets, the concomitant critical temperature thresholds for inactivation of photosystem II (PS II) were studied using a micro fibre optic and a chlorophyll fluorometer mounted to the microscope stage. Chlorophyllous cells of S. capillifolium showed extended freezing cytorrhysis immediately after ice nucleation at -1.1 degrees C in the water in which the leaflets were submersed during the measurement. The occurrence of freezing cytorrhysis, which was visually manifested by cell shrinkage, was highly dynamic and was completed within 2 s. A total reduction of the mean projected diameter of the chloroplast containing area during freezing cytorrhysis from 8.9 to 3.8 microm indicates a cell volume reduction of approximately -82%. Simultaneous measurement of chlorophyll fluorescence of PS II was possible even through the frozen water in which the leaf samples were submersed. Freezing cytorrhysis was accompanied by a sudden rise of basic chlorophyll fluorescence. The critical freezing temperature threshold of PS II was identical to the ice nucleation temperature (-1.1 degrees C). This is significantly above the temperature threshold at which frost damage to S. capillifolium leaflets occurs (-16.1 degrees C; LT(50)) which is higher than observed in most higher plants from the European Alps during summer. High temperature thresholds of PS II were 44.5 degrees C which is significantly below the heat tolerance of chlorophyllous cells (49.9 degrees C; LT(50)). It is demonstrated that light and fluorescence microscopic techniques combined with simultaneous chlorophyll fluorescence measurements may act as a useful tool to study heat, low temperature, and ice-encasement effects on the cellular structure and primary photosynthetic processes of intact leaf tissues.

Mechanisms of Reactive Stroma-Induced Tumorigenesis in Prostate Cancer

DTIC Science & Technology

2016-11-01

PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public... Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT...and co-culture models. We have found that RUNX1 is critical mediator of TGF-beta action in mesenchymal stem /progenitor cells. RUNX1 is critical for

Vesicle-associated membrane protein 2 mediates trafficking of {alpha}5{beta}1 integrin to the plasma membrane

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

Hasan, Nazarul; Hu, Chuan, E-mail: chuan.hu@louisville.edu

2010-01-01

Integrins are major receptors for cell adhesion to the extracellular matrix (ECM). As transmembrane proteins, the levels of integrins at the plasma membrane or the cell surface are ultimately determined by the balance between two vesicle trafficking events: endocytosis of integrins at the plasma membrane and exocytosis of the vesicles that transport integrins. Here, we report that vesicle-associated membrane protein 2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane, is involved in the trafficking of {alpha}5{beta}1 integrin. VAMP2 was present on vesicles containing endocytosed {beta}1 integrin. Small interfering RNA (siRNA) silencing of VAMP2 markedly reduced cellmore » surface {alpha}5{beta}1 and inhibited cell adhesion and chemotactic migration to fibronectin, the ECM ligand of {alpha}5{beta}1, without altering cell surface expression of {alpha}2{beta}1 integrin or {alpha}3{beta}1 integrin. By contrast, silencing of VAMP8, another SNARE protein, had no effect on cell surface expression of the integrins or cell adhesion to fibronectin. In addition, VAMP2-mediated trafficking is involved in cell adhesion to collagen but not to laminin. Consistent with disruption of integrin functions in cell proliferation and survival, VAMP2 silencing diminished proliferation and triggered apoptosis. Collectively, these data indicate that VAMP2 mediates the trafficking of {alpha}5{beta}1 integrin to the plasma membrane and VAMP2-dependent integrin trafficking is critical in cell adhesion, migration and survival.« less

Integrins (alpha7beta1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy.

PubMed Central

Vachon, P H; Xu, H; Liu, L; Loechel, F; Hayashi, Y; Arahata, K; Reed, J C; Wewer, U M; Engvall, E

1997-01-01

Mutations in genes coding for dystrophin, for alpha, beta, gamma, and delta-sarcoglycans, or for the alpha2 chain of the basement membrane component merosin (laminin-2/4) cause various forms of muscular dystrophy. Analyses of integrins showed an abnormal expression and localization of alpha7beta1 isoforms in myofibers of merosin-deficient human patients and mice, but not in dystrophin-deficient or sarcoglycan-deficient humans and animals. It was shown previously that skeletal muscle fibers require merosin for survival and function (Vachon, P.H., F. Loechel, H. Xu, U.M. Wewer, and E. Engvall. 1996. J. Cell Biol. 134:1483-1497). Correction of merosin deficiency in vitro through cell transfection with the merosin alpha2 chain restored the normal localization of alpha7beta1D integrins as well as myotube survival. Overexpression of the apoptosis-suppressing molecule Bcl-2 also promoted the survival of merosin-deficient myotubes, but did not restore a normal expression of alpha7beta1D integrins. Blocking of beta1 integrins in normal myotubes induced apoptosis and severely reduced their survival. These findings (a) identify alpha7beta1D integrins as the de facto receptors for merosin in skeletal muscle; (b) indicate a merosin dependence for the accurate expression and membrane localization of alpha7beta1D integrins in myofibers; (c) provide a molecular basis for the critical role of merosin in myofiber survival; and (d) add new insights to the pathogenesis of neuromuscular disorders. PMID:9312189

N-Methyl-D-aspartate receptor antagonist MK-801 and radical scavengers protect cholinergic nucleus basalis neurons against beta-amyloid neurotoxicity.

PubMed

Harkany, T; Mulder, J; Sasvári, M; Abrahám, I; Kónya, C; Zarándi, M; Penke, B; Luiten, P G; Nyakas, C

1999-04-01

Previous experimental data indicate the involvement of Ca(2+)-related excitotoxic processes, possibly mediated by N-Methyl-D-Aspartate (NMDA) receptors, in beta-amyloid (beta A) neurotoxicity. On the other hand, other lines of evidence support the view that free radical generation is a critical step in the beta A-induced neurodegenerative cascade. In the present study, therefore, a neuroprotective strategy was applied to explore the contributions of each of these pathways in beta A toxicity. beta A(1-42) was injected into the magnocellular nucleus basalis of rats, while neuroprotection was achieved by either single or combined administration of the NMDA receptor antagonist MK-801 (2.5 mg/kg) and/or a vitamin E and C complex (150 mg/kg). The degree of neurodegeneration was determined by testing the animals in consecutive series of behavioral tasks, including elevated plus maze, passive avoidance learning, small open-field and open-field paradigms, followed by acetylcholinesterase (AChE), choline-acetyltransferase (ChAT), and superoxide dismutase (SOD) biochemistry. beta A injected in the nucleus basalis elicited significant anxiety in the elevated plus maze, derangement of passive avoidance learning, and altered spontaneous behaviors in both open-field tasks. A significant decrease in both AChE and ChAT accompanied by a similar decrement of MnSOD, but not of Cu/ZnSOD provided neurochemical substrates for the behavioral changes. Each of the single drug administrations protected against the neurotoxic events, whereas the combined treatment failed to ameliorate beta A toxicity.

Production of beta-glucan and related glucan-hydrolases by Botryosphaeria rhodina.

PubMed

Crognale, S; Bruno, M; Fidaleo, M; Moresi, M; Petruccioli, M

2007-03-01

Characterization of beta-glucan production from Botryosphaeria rhodina DABAC-P82 by detecting simultaneously glucan-hydrolytic enzymes and their localization, culture medium rheology and oxygen transfer. Mycelium growth, beta-glucan production, substrate consumption and glucan-hydrolytic enzymes were monitored both in shaken flasks and in a 3-l stirred-tank bioreactor. Glucan production (19.7 and 15.2 g l(-1), in flask and bioreactor, respectively) was accompanied by extra-cellular and cell-bound beta-glucanase and beta-glucosidase activities. In the bioreactor scale, in the time interval of 0-78 h the apparent viscosity of the culture broth exhibited a general increase; thereafter, it began to reduce, probably because of the above glucan-hydrolytic activities. Moreover, the culture media collected after 45 h behaved as solid-like materials at shear rates smaller than 0.001 s(-1), as pseudo-plastic liquids in the middle shear rate range and as Newtonian ones at shear rates greater than 1000 s(-1). The greatest beta-glucan accumulation in the bioreactor was found to be associated with nitrogen and dissolved oxygen concentrations smaller than 0.15 g l(-1) and 25%, respectively, and with the peak points of the glucan-degrading enzymes. A careful analysis of the critical factors (such as, culture broth rheology, oxygen mass transfer and glucan-hydrolytic enzymes) limiting the beta-glucan production by B. rhodina is a prerequisite to maximize beta-glucan yield and production, as well as to define the process flow sheet capable of maximizing biopolymer recovery, solvent re-utilization and glucose consumption.

Rossitsa River Basin: Flood Hazard and Risk Identification

NASA Astrophysics Data System (ADS)

Mavrova-Guirguinova, Maria; Pencheva, Denislava

2017-04-01

The process of Flood Risk Management Planning and adaptation of measures for flood risk reduction as the Early Warning provoke the necessity of surveys involving Identification aspects. This project presents risk identification combining two lines of analysis: (1) Creation a mathematical model of rainfall-runoff processes in a watershed based on limited number of observed input and output variables; (2) Procedures for determination of critical thresholds - discharges/water levels corresponding to certain consequences. The pilot region is Rossitsa river basin, Sevlievo, Bulgaria. The first line of analysis follows next steps: (a) Creation and calibration of Unit Hydrograph Models based on limited number of observed data for discharge and precipitation; The survey at the selected region has 22 observations for excess rainfall and discharge. (b) The relations of UHM coefficients from the input parameters have been determined statistically, excluding the ANN model of the run-off coefficient as a function of 3 parameters (amount of precipitation two days before, soil condition, intensity of the rainfall) where a feedforward neural network is used. (c) Additional simulations with UHM aiming at generation of synthetic data for rainfall-runoff events, which extend the range of observed data; (d) Training, validation and testing a generalized regional ANN Model for discharge forecasting with 4 input parameters, where the training data set consists of synthetic data, validation and testing data sets consists of observations. A function between consequences and discharges has been reached in the second line of analysis concerning critical hazard levels determination. Unsteady simulations with the hydraulic model using three typical hydrographs for determination of the existing time for reaction from one to upper critical threshold are made. Correction of the critical thresholds aiming at providing necessary time for reaction between the thresholds and probability analysis of the finally determined critical thresholds are made. The result of the described method is a Catalogue for off-line flood hazard and risk identification. It can be used as interactive computer system, based on simulations of the ANN "Catalogue". Flood risk identification of the future rainfall event is made in a multi-dimensional space for each kind of soil conditions (dry, average wet and wet condition) and observed amount of precipitation two days before. Rainfall-runoff scenarios in case of intensive rainfall or sustained rainfall (more than 6 hours) are taken into account. Critical thresholds and hazard zones needed of specific operative activities (rescue and recovery) corresponded to each of the regulated flood protection levels (unite, municipality, regional or national) are presented. The Catalogue gives the opportunity for flood hazard scenarios extraction. Regarding that, the Catalogue is useful on the prevention stage of flood protection planning (emergency operations, measures and resources for their implementation planning) and creation of scenarios for training the Emergency Plans. Concerning application for Early Warning, it gives approximate forecast for flood hazard. The Catalogue supplies the necessary time for reaction of about 24 hours. Thus, Early Warning is possible to the responsible authorities, all parts if the Unified Rescue System, members of suitable Headquarters for disaster protection (on municipality, region or national level).

Nociception at the diabetic foot, an uncharted territory

PubMed Central

Chantelau, Ernst A

2015-01-01

The diabetic foot is characterised by painless foot ulceration and/or arthropathy; it is a typical complication of painless diabetic neuropathy. Neuropathy depletes the foot skin of intraepidermal nerve fibre endings of the afferent A-delta and C-fibres, which are mostly nociceptors and excitable by noxious stimuli only. However, some of them are cold or warm receptors whose functions in diabetic neuropathy have frequently been reported. Hence, it is well established by quantitative sensory testing that thermal detection thresholds at the foot skin increase during the course of painless diabetic neuropathy. Pain perception (nociception), by contrast, has rarely been studied. Recent pilot studies of pinprick pain at plantar digital skinfolds showed that the perception threshold was always above the upper limit of measurement of 512 mN (equivalent to 51.2 g) at the diabetic foot. However, deep pressure pain perception threshold at musculus abductor hallucis was beyond 1400 kPa (equivalent to 14 kg; limit of measurement) only in every fifth case. These discrepancies of pain perception between forefoot and hindfoot, and between skin and muscle, demand further study. Measuring nociception at the feet in diabetes opens promising clinical perspectives. A critical nociception threshold may be quantified (probably corresponding to a critical number of intraepidermal nerve fibre endings), beyond which the individual risk of a diabetic foot rises appreciably. Staging of diabetic neuropathy according to nociception thresholds at the feet is highly desirable as guidance to an individualised injury prevention strategy. PMID:25897350

Lower-upper-threshold correlation for underwater range-gated imaging self-adaptive enhancement.

PubMed

Sun, Liang; Wang, Xinwei; Liu, Xiaoquan; Ren, Pengdao; Lei, Pingshun; He, Jun; Fan, Songtao; Zhou, Yan; Liu, Yuliang

2016-10-10

In underwater range-gated imaging (URGI), enhancement of low-brightness and low-contrast images is critical for human observation. Traditional histogram equalizations over-enhance images, with the result of details being lost. To compress over-enhancement, a lower-upper-threshold correlation method is proposed for underwater range-gated imaging self-adaptive enhancement based on double-plateau histogram equalization. The lower threshold determines image details and compresses over-enhancement. It is correlated with the upper threshold. First, the upper threshold is updated by searching for the local maximum in real time, and then the lower threshold is calculated by the upper threshold and the number of nonzero units selected from a filtered histogram. With this method, the backgrounds of underwater images are constrained with enhanced details. Finally, the proof experiments are performed. Peak signal-to-noise-ratio, variance, contrast, and human visual properties are used to evaluate the objective quality of the global and regions of interest images. The evaluation results demonstrate that the proposed method adaptively selects the proper upper and lower thresholds under different conditions. The proposed method contributes to URGI with effective image enhancement for human eyes.

Physical activity, inflammatory biomarkers in gingival crevicular fluid and periodontitis.

PubMed

Sanders, Anne E; Slade, Gary D; Fitzsimmons, Tracy R; Bartold, Peter Mark

2009-05-01

To examine the associations of physical activity with interleukin 1-beta (IL-1beta), C-reactive protein (CRP) and periodontitis and to investigate whether any relationship between physical activity and inflammatory mediators differs between periodontitis cases and non-cases. In this population-based case control study of Australians aged 18+ years, dentists conducted oral epidemiologic examinations identifying cases with moderate or severe periodontitis and periodontally healthy controls. Gingival crevicular fluid samples collected during examinations were analysed for inflammatory biomarkers. Subject-completed questionnaires assessed leisure-time physical activity. Exposure odds ratios (ORs) were estimated in multivariable logistic regression models adjusting for periodontitis risk indicators. Of 751 subjects (359 cases, 392 controls), those meeting a prescribed threshold for leisure-time physical activity had lower adjusted odds of elevated IL-1beta: OR=0.69, (95% CI=0.50-0.94) and detectable CRP: OR=0.70 (0.50-0.98) than less active adults. Physical activity was not associated with periodontitis: OR=1.14 (0.80-1.62). Periodontitis modified the association between levels of physical activity and detectable CRP. Increasing quartiles of physically activity were associated with decreasing probability of detectable CRP, but the effect was limited to periodontitis cases and was not apparent among non-cases. Leisure-time physical activity may protect against an excessive inflammatory response in periodontitis.

Measuring and Modeling Xenon Uptake in Plastic Beta-Cells

NASA Astrophysics Data System (ADS)

Suarez, R.; Hayes, J. C.; Harper, W. W.; Humble, P.; Ripplinger, M. D.; Stephenson, D. E.; Williams, R. M.

2013-12-01

The precision of the stable xenon volume measurement in atmospheric monitoring radio-xenon systems is a critical parameter used to determine the activity concentration of a radio-xenon sample. Typically these types of systems use a plastic scintillating beta-cell as part of a beta-gamma detection scheme to measure the radioactivity present in the gas sample. Challenges arise when performing the stable xenon calculation during or after radioactive counting of the sample due to xenon uptake into the plastic beta-cells. Plastic beta cells can adsorb as much as 5% of the sample during counting. If quantification is performed after counting, the uptake of xenon into the plastic results in an underestimation of the xenon volume measurement. This behavior also causes what is typically known as 'memory effect' in the cell. Experiments were conducted using a small volume low pressure range thermal conductivity sensor to quantify the amount of xenon uptake into the cell over a given period of time. Understanding the xenon uptake in the cell provides a better estimate of the stable volume which improves the overall measurement capability of the system. The results from these experiments along with modeling will be presented.

Population dynamics of obligate cooperators

PubMed Central

Courchamp, F.; Grenfell, B.; Clutton-Brock, T.

1999-01-01

Obligate cooperative breeding species demonstrate a high rate of group extinction, which may be due to the existence of a critical number of helpers below which the group cannot subsist. Through a simple model, we study the population dynamics of obligate cooperative breeding species, taking into account the existence of a lower threshold below which the instantaneous growth rate becomes negative. The model successively incorporates (i) a distinction between species that need helpers for reproduction, survival or both, (ii) the existence of a migration rate accounting for dispersal, and (iii) stochastic mortality to simulate the effects of random catastrophic events. Our results suggest that the need for a minimum number of helpers increases the risk of extinction for obligate cooperative breeding species. The constraint imposed by this threshold is higher when helpers are needed for reproduction only or for both reproduction and survival. By driving them below this lower threshold, stochastic mortality of lower amplitude and/or lower frequency than for non-cooperative breeders may be sufficient to cause the extinction of obligate cooperative breeding groups. Migration may have a buffering effect only for groups where immigration is higher than emigration; otherwise (when immigrants from nearby groups are not available) it lowers the difference between actual group size and critical threshold, thereby constituting a higher constraint.

Thresholding of auditory cortical representation by background noise

PubMed Central

Liang, Feixue; Bai, Lin; Tao, Huizhong W.; Zhang, Li I.; Xiao, Zhongju

2014-01-01

It is generally thought that background noise can mask auditory information. However, how the noise specifically transforms neuronal auditory processing in a level-dependent manner remains to be carefully determined. Here, with in vivo loose-patch cell-attached recordings in layer 4 of the rat primary auditory cortex (A1), we systematically examined how continuous wideband noise of different levels affected receptive field properties of individual neurons. We found that the background noise, when above a certain critical/effective level, resulted in an elevation of intensity threshold for tone-evoked responses. This increase of threshold was linearly dependent on the noise intensity above the critical level. As such, the tonal receptive field (TRF) of individual neurons was translated upward as an entirety toward high intensities along the intensity domain. This resulted in preserved preferred characteristic frequency (CF) and the overall shape of TRF, but reduced frequency responding range and an enhanced frequency selectivity for the same stimulus intensity. Such translational effects on intensity threshold were observed in both excitatory and fast-spiking inhibitory neurons, as well as in both monotonic and nonmonotonic (intensity-tuned) A1 neurons. Our results suggest that in a noise background, fundamental auditory representations are modulated through a background level-dependent linear shifting along intensity domain, which is equivalent to reducing stimulus intensity. PMID:25426029

Synthetic hardware performance analysis in virtualized cloud environment for healthcare organization.

PubMed

Tan, Chee-Heng; Teh, Ying-Wah

2013-08-01

The main obstacles in mass adoption of cloud computing for database operations in healthcare organization are the data security and privacy issues. In this paper, it is shown that IT services particularly in hardware performance evaluation in virtual machine can be accomplished effectively without IT personnel gaining access to actual data for diagnostic and remediation purposes. The proposed mechanisms utilized the hypothetical data from TPC-H benchmark, to achieve 2 objectives. First, the underlying hardware performance and consistency is monitored via a control system, which is constructed using TPC-H queries. Second, the mechanism to construct stress-testing scenario is envisaged in the host, using a single or combination of TPC-H queries, so that the resource threshold point can be verified, if the virtual machine is still capable of serving critical transactions at this constraining juncture. This threshold point uses server run queue size as input parameter, and it serves 2 purposes: It provides the boundary threshold to the control system, so that periodic learning of the synthetic data sets for performance evaluation does not reach the host's constraint level. Secondly, when the host undergoes hardware change, stress-testing scenarios are simulated in the host by loading up to this resource threshold level, for subsequent response time verification from real and critical transactions.

SKI knockdown inhibits human melanoma tumor growth in vivo.

PubMed

Chen, Dahu; Lin, Qiushi; Box, Neil; Roop, Dennis; Ishii, Shunsuke; Matsuzaki, Koichi; Fan, Tao; Hornyak, Thomas J; Reed, Jon A; Stavnezer, Ed; Timchenko, Nikolai A; Medrano, Estela E

2009-12-01

The SKI protein represses the TGF-beta tumor suppressor pathway by associating with the Smad transcription factors. SKI is upregulated in human malignant melanoma tumors in a disease-progression manner and its overexpression promotes proliferation and migration of melanoma cells in vitro. The mechanisms by which SKI antagonizes TGF-beta signaling in vivo have not been fully elucidated. Here we show that human melanoma cells in which endogenous SKI expression was knocked down by RNAi produced minimal orthotopic tumor xenograft nodules that displayed low mitotic rate and prominent apoptosis. These minute tumors exhibited critical signatures of active TGF-beta signaling including high levels of nuclear Smad3 and p21(Waf-1), which are not found in the parental melanomas. To understand how SKI promotes tumor growth we used gain- and loss-of-function approaches and found that simultaneously to blocking the TGF-beta-growth inhibitory pathway, SKI promotes the switch of Smad3 from tumor suppression to oncogenesis by favoring phosphorylations of the Smad3 linker region in melanoma cells but not in normal human melanocytes. In this context, SKI is required for preventing TGF-beta-mediated downregulation of the oncogenic protein c-MYC, and for inducing the plasminogen activator inhibitor-1, a mediator of tumor growth and angiogenesis. Together, the results indicate that SKI exploits multiple regulatory levels of the TGF-beta pathway and its deficiency restores TGF-beta tumor suppressor and apoptotic activities in spite of the likely presence of oncogenic mutations in melanoma tumors.

Confirmatory analysis of 17beta-boldenone, 17alpha-boldenone and androsta-1,4-diene-3,17-dione in bovine urine, faeces, feed and skin swab samples by liquid chromatography-electrospray ionisation tandem mass spectrometry.

PubMed

Nielen, Michel W F; Rutgers, Paula; van Bennekom, Eric O; Lasaroms, Johan J P; van Rhijn, J A Hans

2004-03-05

The origin, i.e. natural occurrence or illegal treatment, of findings of 17alpha-boldenone (alpha-Bol) and 17beta-boldenone (beta-Bol) in urine and faeces of cattle is under debate within the European Union. A liquid chromatographic positive ion electrospray tandem mass spectrometric method is presented for the confirmatory analysis of 17beta-boldenone, 17alpha-boldenone and an important metabolite/precursor androsta-1,4-diene-3,17-dione (ADD), using deuterium-labelled 17beta-boldenone (beta-Bol-d3) as internal standard. Detailed sample preparation procedures were developed for a variety of sample matrices such as bovine urine, faeces, feed and skin swab samples. The method was validated as a quantitative confirmatory method according to the latest EU guidelines and shows good precision, linearity and accuracy data, and CCalpha and CCbeta values of 0.1-0.3 and 0.4-1.0 ng/ml, respectively. Currently, the method has been successfully applied to suspect urine samples for more than a year, and occasionally to faeces, feed and swab samples as well. Results obtained from untreated and treated animals are given and their impact on the debate about the origin of residues of 17beta-boldenone is critically discussed. Finally, preliminary data about the degree of conjugation of boldenone residues are presented and a simple procedure for discrimination between residues from abuse versus natural origin is proposed.

Association between anti-beta2 glycoprotein I antibodies and renal glomerular C4d deposition in lupus nephritis patients with glomerular microthrombosis: a prospective study of 155 cases.

PubMed

Shen, Y; Chen, X-W; Sun, C-Y; Dai, M; Yan, Y-C; Yang, C-D

2010-09-01

Glomerular microthrombosis (GMT) is a common vascular change in patients with lupus nephritis (LN). The mechanism underlying GMT is still unknown. In our previous study, we found that the level of IgG anti-beta2 glycoprotein I (beta2GPI) antibodies was higher in the LN-GMT group than in the LN-non-GMT group, which indicated that anti-beta2GPI antibodies may play a role in GMT formation. Many studies have demonstrated that the activation of the classical complement pathway may play a critical role in fetal loss and aPL-induced thrombosis formation. To investigate whether complement activation plays a role in GMT formation and to evaluate its relationship with aPL, we prospectively investigated deposition of C4d in 155 renal biopsy specimens of LN patients. The results revealed a strong relationship between the intensity of glomerular C4d staining and the presence of microthrombi (p < 0.001). The detection rate of IgG anti-beta2GPI antibodies was higher in the LN-GMT group than in the LN-non-GMT group (p < 0.05). Further, the intensity of glomerular C4d staining was significantly related with IgG anti-beta2GPI antibodies (p < 0.05). The results of our study suggest that anti-beta2GPI antibodies may play a role in GMT formation, and this process might involve complement activation.

Method for preparing superconductors

DOEpatents

Dahlgren, Shelley D.

1976-01-01

A superconductor having an equiaxed fine grain beta-tungsten crystalline structure found to have improved high field critical current densities is prepared by sputter-depositing superconductive material onto a substrate cooled to below 200.degree. C. and heat-treating the deposited material.

Modelling the regulatory system for diabetes mellitus with a threshold window

NASA Astrophysics Data System (ADS)

Yang, Jin; Tang, Sanyi; Cheke, Robert A.

2015-05-01

Piecewise (or non-smooth) glucose-insulin models with threshold windows for type 1 and type 2 diabetes mellitus are proposed and analyzed with a view to improving understanding of the glucose-insulin regulatory system. For glucose-insulin models with a single threshold, the existence and stability of regular, virtual, pseudo-equilibria and tangent points are addressed. Then the relations between regular equilibria and a pseudo-equilibrium are studied. Furthermore, the sufficient and necessary conditions for the global stability of regular equilibria and the pseudo-equilibrium are provided by using qualitative analysis techniques of non-smooth Filippov dynamic systems. Sliding bifurcations related to boundary node bifurcations were investigated with theoretical and numerical techniques, and insulin clinical therapies are discussed. For glucose-insulin models with a threshold window, the effects of glucose thresholds or the widths of threshold windows on the durations of insulin therapy and glucose infusion were addressed. The duration of the effects of an insulin injection is sensitive to the variation of thresholds. Our results indicate that blood glucose level can be maintained within a normal range using piecewise glucose-insulin models with a single threshold or a threshold window. Moreover, our findings suggest that it is critical to individualise insulin therapy for each patient separately, based on initial blood glucose levels.

A Critical, Nonlinear Threshold Dictates Bacterial Invasion and Initial Kinetics During Influenza

NASA Astrophysics Data System (ADS)

Smith, Amber M.; Smith, Amanda P.

2016-12-01

Secondary bacterial infections increase morbidity and mortality of influenza A virus (IAV) infections. Bacteria are able to invade due to virus-induced depletion of alveolar macrophages (AMs), but this is not the only contributing factor. By analyzing a kinetic model, we uncovered a nonlinear initial dose threshold that is dependent on the amount of virus-induced AM depletion. The threshold separates the growth and clearance phenotypes such that bacteria decline for dose-AM depletion combinations below the threshold, stay constant near the threshold, and increase above the threshold. In addition, the distance from the threshold correlates to the growth rate. Because AM depletion changes throughout an IAV infection, the dose requirement for bacterial invasion also changes accordingly. Using the threshold, we found that the dose requirement drops dramatically during the first 7d of IAV infection. We then validated these analytical predictions by infecting mice with doses below or above the predicted threshold over the course of IAV infection. These results identify the nonlinear way in which two independent factors work together to support successful post-influenza bacterial invasion. They provide insight into coinfection timing, the heterogeneity in outcome, the probability of acquiring a coinfection, and the use of new therapeutic strategies to combat viral-bacterial coinfections.

A Critical, Nonlinear Threshold Dictates Bacterial Invasion and Initial Kinetics During Influenza.

PubMed

Smith, Amber M; Smith, Amanda P

2016-12-15

Secondary bacterial infections increase morbidity and mortality of influenza A virus (IAV) infections. Bacteria are able to invade due to virus-induced depletion of alveolar macrophages (AMs), but this is not the only contributing factor. By analyzing a kinetic model, we uncovered a nonlinear initial dose threshold that is dependent on the amount of virus-induced AM depletion. The threshold separates the growth and clearance phenotypes such that bacteria decline for dose-AM depletion combinations below the threshold, stay constant near the threshold, and increase above the threshold. In addition, the distance from the threshold correlates to the growth rate. Because AM depletion changes throughout an IAV infection, the dose requirement for bacterial invasion also changes accordingly. Using the threshold, we found that the dose requirement drops dramatically during the first 7d of IAV infection. We then validated these analytical predictions by infecting mice with doses below or above the predicted threshold over the course of IAV infection. These results identify the nonlinear way in which two independent factors work together to support successful post-influenza bacterial invasion. They provide insight into coinfection timing, the heterogeneity in outcome, the probability of acquiring a coinfection, and the use of new therapeutic strategies to combat viral-bacterial coinfections.

Experience-dependent emergence of beta and gamma band oscillations in the primary visual cortex during the critical period

PubMed Central

Chen, Guang; Rasch, Malte J.; Wang, Ran; Zhang, Xiao-hui

2015-01-01

Neural oscillatory activities have been shown to play important roles in neural information processing and the shaping of circuit connections during development. However, it remains unknown whether and how specific neural oscillations emerge during a postnatal critical period (CP), in which neuronal connections are most substantially modified by neural activity and experience. By recording local field potentials (LFPs) and single unit activity in developing primary visual cortex (V1) of head-fixed awake mice, we here demonstrate an emergence of characteristic oscillatory activities during the CP. From the pre-CP to CP, the peak frequency of spontaneous fast oscillatory activities shifts from the beta band (15–35 Hz) to the gamma band (40–70 Hz), accompanied by a decrease of cross-frequency coupling (CFC) and broadband spike-field coherence (SFC). Moreover, visual stimulation induced a large increase of beta-band activity but a reduction of gamma-band activity specifically from the CP onwards. Dark rearing of animals from the birth delayed this emergence of oscillatory activities during the CP, suggesting its dependence on early visual experience. These findings suggest that the characteristic neuronal oscillatory activities emerged specifically during the CP may represent as neural activity trait markers for the experience-dependent maturation of developing visual cortical circuits. PMID:26648548

Bench-level characterization of a CMOS standard-cell D-latch using alpha-particle sensitive test circuits

NASA Technical Reports Server (NTRS)

Blaes, B. R.; Soli, G. A.; Buehler, M. G.

1991-01-01

A methodology is described for predicting the SEU susceptibility of a standard-cell D-latch using an alpha-particle sensitive SRAM, SPICE critical charge simulation results, and alpha-particle interaction physics. Measurements were made on a 1.6-micron n-well CMOS 4-kb test SRAM irradiated with an Am-241 alpha-particle source. A collection depth of 6.09 micron was determined using these results and TRIM computer code. Using this collection depth and SPICE derived critical charge results on the latch design, an LET threshold of 34 MeV sq cm/mg was predicted. Heavy ion tests were then performed on the latch and an LET threshold of 41 MeV sq cm/mg was determined.

Phase-locking transition in a chirped superconducting Josephson resonator.

PubMed

Naaman, O; Aumentado, J; Friedland, L; Wurtele, J S; Siddiqi, I

2008-09-12

We observe a sharp threshold for dynamic phase locking in a high-Q transmission line resonator embedded with a Josephson tunnel junction, and driven with a purely ac, chirped microwave signal. When the drive amplitude is below a critical value, which depends on the chirp rate and is sensitive to the junction critical current I0, the resonator is only excited near its linear resonance frequency. For a larger amplitude, the resonator phase locks to the chirped drive and its amplitude grows until a deterministic maximum is reached. Near threshold, the oscillator evolves smoothly in one of two diverging trajectories, providing a way to discriminate small changes in I0 with a nonswitching detector, with potential applications in quantum state measurement.

Stability analysis of the high poloidal bet scenario on DIII-Dtowards operation athigher plasma current

NASA Astrophysics Data System (ADS)

Guo, W. F.; Gong, X. Z.; Huang, J.; Ren, Q. L.; Qian, J. P.; Ding, S. Y.; Pan, C. K.; Li, G. Q.; Xia, T. Y.; Garofalo, A. M.; Lao, L.; Hyatt, A.; Ferron, J.; Meneghini, O.; Liu, Y. Q.; McClenaghan, J.; Holcomb, C. T.

2017-10-01

The high poloidal beta scenario with plasma current IP 600 kA and large-radius internal transport barrier (ITB) on DIII-D is subject to n =1 MHD kink modes when the current profile becomes very broad at internal inductance values li 0.5-0.6. It is desirable to extend this scenario to higer plasma current ( 1 MA) for highernormalized fusionperformance. However, higher current at constant normalized beta, ?N 3, would reducethe poloidal bet, ?P, below the threshold for ITB sustainment, observed at ?P 1.9. Thus, to avoid loss of the IT, ?N?? must be increased together with IP while avoiding the kink instability. MHD analysis is presented that explains possible paths to high ?N stability limit for the kink mode in tis scenario. Work supported by National Magnetic Confinement Fusion Program of Chin under 2015GB110001 and 2015GB102000 - National Natural Science Foundation of China under Grant No. 1147521 and by US DOE under DE-FC02-04ER54698.

High frequency fishbone driven by passing energetic ions in tokamak plasmas

NASA Astrophysics Data System (ADS)

Wang, Feng; Yu, L. M.; Fu, G. Y.; Shen, Wei

2017-05-01

High frequency fishbone instability driven by passing energetic ions was first reported in the Princeton beta experiment with tangential neutral-beam-injection (Heidbrink et al 1986 Phys. Rev. Lett. 57 835-8). It could play an important role for ITER-like burning plasmas, where α particles are mostly passing particles. In this work, a generalized energetic ion distribution function and finite drift orbit width effect are considered to improve the theoretical model for passing particle driving fishbone instability. For purely passing energetic ions with zero drift orbit width, the kinetic energy δ {{W}k} is derived analytically. The derived analytic expression is more accurate as compared to the result of previous work (Wang 2001 Phys. Rev. Lett. 86 5286-8). For a generalized energetic ion distribution function, the fishbone dispersion relation is derived and is solved numerically. Numerical results show that broad and off-axis beam density profiles can significantly increase the beam ion beta threshold {βc} for instability and decrease mode frequency.

The MAJORANA DEMONSTRATOR: A search for neutrinoless double-beta decay of germanium-76

NASA Astrophysics Data System (ADS)

Schubert, Alexis; Majorana Collaboration

2011-04-01

Observation of neutrinoless double-beta decay (0 νββ) could determine whether the neutrino is a Majorana particle and may provide information on neutrino mass. The MAJORANA Collaboration will search for 0 νββ of 76Ge in an array of germanium detectors enriched to 86% in 76Ge. Germanium detectors are a well-understood technology and have the benefits of excellent energy resolution, a high Q-value, and the ability to act as source and detector. The p-type point contact germanium detectors chosen by the MAJORANA Collaboration provide low noise, low energy threshold, and some ability to distinguish between the signal and background events. MAJORANA is constructing the DEMONSTRATOR, which will be used to conduct research and development toward a tonne-scale Ge experiment. The DEMONSTRATOR will be installed deep underground and will contain 40 kg of Ge deployed in an ultra-low-background shielded environment. Research supported by DOE under contracts DE-AC05-00OR22725 and DE-FG02-97ER41020.

The Beta-Delayed Proton and Gamma Decay of 27P for Nuclear Astrophysics

NASA Astrophysics Data System (ADS)

McCleskey, E.; Banu, A.; McCleskey, M.; Roeder, B.; Saastamoinen, A.; Spiridon, A.; Trache, L.; Tribble, R. E.; Davinson, T.; Doherty, D.; Lotay, G. J.; Wallace, J.; Woods, P. J.

2013-10-01

The main creation site of 26Al is currently under debate. The reactions for its creation or destruction are also not completely known. When 26Al is created in novae, the reaction chain is: 24Mg(p,γ)25Al(β + v)25Mg(p,γ)26Al, but this chain can be by-passed by another chain: 25Al(p,γ)26Si(p,γ)27P and it can also be destroyed directly. Another way to by-pass it is through 26mAl(p,γ)27Si* which is dominated by resonant capture. Using the Momentum Achromat Recoil Spectrometer (MARS) at the Texas A&M Cyclotron Institute and inverse kinematics, this destruction reaction was studied by the beta-delayed proton and gamma decay of 27P. Due to selection rules, states populated above the proton threshold in the compound system (27Si*) can decay to 26mAl, which are the states of interest for the capture reaction. James Madison University, VA, USA.

Picosecond electric-field-induced threshold switching in phase-change materials [THz-induced threshold switching and crystallization of phase-change materials

DOE PAGES

Zalden, Peter; Shu, Michael J.; Chen, Frank; ...

2016-08-05

Many chalcogenide glasses undergo a breakdown in electronic resistance above a critical field strength. Known as threshold switching, this mechanism enables field-induced crystallization in emerging phase-change memory. Purely electronic as well as crystal nucleation assisted models have been employed to explain the electronic breakdown. Here, picosecond electric pulses are used to excite amorphous Ag 4In 3Sb 67Te 26. Field-dependent reversible changes in conductivity and pulse-driven crystallization are observed. The present results show that threshold switching can take place within the electric pulse on subpicosecond time scales—faster than crystals can nucleate. As a result, this supports purely electronic models of thresholdmore » switching and reveals potential applications as an ultrafast electronic switch.« less

Flood and landslide warning based on rainfall thresholds and soil moisture indexes: the HEWS (Hydrohazards Early Warning System) for Sicily

NASA Astrophysics Data System (ADS)

Brigandì, Giuseppina; Tito Aronica, Giuseppe; Bonaccorso, Brunella; Gueli, Roberto; Basile, Giuseppe

2017-09-01

The main focus of the paper is to present a flood and landslide early warning system, named HEWS (Hydrohazards Early Warning System), specifically developed for the Civil Protection Department of Sicily, based on the combined use of rainfall thresholds, soil moisture modelling and quantitative precipitation forecast (QPF). The warning system is referred to 9 different Alert Zones in which Sicily has been divided into and based on a threshold system of three different increasing critical levels: ordinary, moderate and high. In this system, for early flood warning, a Soil Moisture Accounting (SMA) model provides daily soil moisture conditions, which allow to select a specific set of three rainfall thresholds, one for each critical level considered, to be used for issue the alert bulletin. Wetness indexes, representative of the soil moisture conditions of a catchment, are calculated using a simple, spatially-lumped rainfall-streamflow model, based on the SCS-CN method, and on the unit hydrograph approach, that require daily observed and/or predicted rainfall, and temperature data as input. For the calibration of this model daily continuous time series of rainfall, streamflow and air temperature data are used. An event based lumped rainfall-runoff model has been, instead, used for the derivation of the rainfall thresholds for each catchment in Sicily characterised by an area larger than 50 km2. In particular, a Kinematic Instantaneous Unit Hydrograph based lumped rainfall-runoff model with the SCS-CN routine for net rainfall was developed for this purpose. For rainfall-induced shallow landslide warning, empirical rainfall thresholds provided by Gariano et al. (2015) have been included in the system. They were derived on an empirical basis starting from a catalogue of 265 shallow landslides in Sicily in the period 2002-2012. Finally, Delft-FEWS operational forecasting platform has been applied to link input data, SMA model and rainfall threshold models to produce warning on a daily basis for the entire region.

Development of a real-time PCR method for the differential detection and quantification of four solanaceae in GMO analysis: potato (Solanum tuberosum), tomato (Solanum lycopersicum), eggplant (Solanum melongena), and pepper (Capsicum annuum).

PubMed

Chaouachi, Maher; El Malki, Redouane; Berard, Aurélie; Romaniuk, Marcel; Laval, Valérie; Brunel, Dominique; Bertheau, Yves

2008-03-26

The labeling of products containing genetically modified organisms (GMO) is linked to their quantification since a threshold for the presence of fortuitous GMOs in food has been established. This threshold is calculated from a combination of two absolute quantification values: one for the specific GMO target and the second for an endogenous reference gene specific to the taxon. Thus, the development of reliable methods to quantify GMOs using endogenous reference genes in complex matrixes such as food and feed is needed. Plant identification can be difficult in the case of closely related taxa, which moreover are subject to introgression events. Based on the homology of beta-fructosidase sequences obtained from public databases, two couples of consensus primers were designed for the detection, quantification, and differentiation of four Solanaceae: potato (Solanum tuberosum), tomato (Solanum lycopersicum), pepper (Capsicum annuum), and eggplant (Solanum melongena). Sequence variability was studied first using lines and cultivars (intraspecies sequence variability), then using taxa involved in gene introgressions, and finally, using taxonomically close taxa (interspecies sequence variability). This study allowed us to design four highly specific TaqMan-MGB probes. A duplex real time PCR assay was developed for simultaneous quantification of tomato and potato. For eggplant and pepper, only simplex real time PCR tests were developed. The results demonstrated the high specificity and sensitivity of the assays. We therefore conclude that beta-fructosidase can be used as an endogenous reference gene for GMO analysis.

Steroid profiles of professional soccer players: an international comparative study.

PubMed

Strahm, E; Sottas, P-E; Schweizer, C; Saugy, M; Dvorak, J; Saudan, C

2009-12-01

Urinary steroid profiling is used in doping controls to detect testosterone abuse. A testosterone over epitestosterone (T/E) ratio exceeding 4.0 is considered as suspicious of testosterone administration, irrespectively of individual heterogeneous factors such as the athlete's ethnicity. A deletion polymorphism in the UGT2B17 gene was demonstrated to account for a significant part of the interindividual variability in the T/E between Caucasians and Asians. Here, the variability of urinary steroid profiles was examined in a widely heterogeneous cohort of professional soccer players. The steroid profile of 57 Africans, 32 Asians, 50 Caucasians and 32 Hispanics was determined by gas chromatography-mass spectrometry. Significant differences have been observed between all ethnic groups. After estimation of the prevalence of the UGT2B17 deletion/deletion genotype (African: 22%; Asian: 81%; Caucasian: 10%; Hispanic: 7%), ethnic-specific thresholds were developed for a specificity of 99% for the T/E (African: 5.6; Asian: 3.8; Caucasian: 5.7; Hispanic: 5.8). Finally, another polymorphism could be hypothesised in Asians based on specific concentration ratio of 5alpha-/5beta-androstane-3alpha,17beta-diol in urine. These results demonstrate that a unique and non-specific threshold to evidence testosterone misuse is not fit for purpose. An athlete's endocrinological passport consisting of a longitudinal follow-up together with the ethnicity and/or the genotype would strongly enhance the detection of testosterone abuse. Finally, additional genotyping studies should be undertaken to determine whether the remaining unexplained disparities have an environmental or a genetic origin.

Abnormality of G-protein-coupled receptor kinases at prodromal and early stages of Alzheimer's disease: an association with early beta-amyloid accumulation.

PubMed

Suo, Zhiming; Wu, Min; Citron, Bruce A; Wong, Gwendolyn T; Festoff, Barry W

2004-03-31

Overwhelming evidence indicates that the effects of beta-amyloid (Abeta) are dose dependent both in vitro and in vivo, which implies that Abeta is not directly detrimental to brain cells until it reaches a threshold concentration. In an effort to understand early Alzheimer's disease (AD) pathogenesis, this study focused on the effects of subthreshold soluble Abeta and the underlying molecular mechanisms in murine microglial cells and an AD transgenic mouse model. We found that there were two phases of dose-dependent Abeta effects on microglial cells: at the threshold of 5 microm and above, Abeta directly induced tumor necrosis factor-alpha (TNF-alpha) release, and at subthreshold doses, Abeta indirectly potentiated TNF-alpha release induced by certain G-protein-coupled receptor (GPCR) activators. Mechanistic studies revealed that subthreshold Abeta pretreatment in vitro reduced membrane GPCR kinase-2/5 (GRK2/5), which led to retarded GPCR desensitization, prolonged GPCR signaling, and cellular hyperactivity to GPCR agonists. Temporal analysis in an early-onset AD transgenic model, CRND8 mice, revealed that the membrane (functional) GRK2/5 in brain cortices were significantly reduced. More importantly, such a GRK abnormality took place before cognitive decline and changed in a manner corresponding with the mild to moderate soluble Abeta accumulation in these transgenic mice. Together, this study not only discovered a novel link between subthreshold Abeta and GRK dysfunction, it also demonstrated that the GRK abnormality in vivo occurs at prodromal and early stages of AD.

Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta.

PubMed

Li, S; Ballou, L R; Morham, S G; Blatteis, C M

2001-08-10

Various lines of evidence have implicated cyclooxygenase (COX)-2 as a modulator of the fever induced by the exogenous pyrogen lipopolysaccharide (LPS). Thus, treatment with specific inhibitors of COX-2 suppresses the febrile response without affecting basal body (core) temperature (T(c)). Furthermore, COX-2 gene-ablated mice are unable to develop a febrile response to intraperitoneal (i.p.) LPS, whereas their COX-1-deficient counterparts produce fevers not different from their wild-type (WT) controls. To extend the apparently critical role of COX-2 for LPS-induced fevers to fevers produced by endogenous pyrogens, we studied the thermal responses of COX-1- and COX-2 congenitally deficient mice to i.p. and intracerebroventricular (i.c.v.) injections of recombinant murine (rm) interleukin (IL)-1beta. We also assessed the effects of one selective COX-1 inhibitor, SC-560, and two selective COX-2 inhibitors, nimesulide (NIM) and dimethylfuranone (DFU), on the febrile responses of WT and COX-1(-/-) mice to LPS and rmIL-1beta, i.p. Finally, we verified the integrity of the animals' responses to PGE2, i.c.v. I.p. and i.c.v. rmIL-1beta induced similar fevers in WT and COX-1 knockout mice, but provoked no rise in the T(c)s of COX-2 null mutants. The fever produced in WT mice by i.p. LPS was not affected by SC-560, but it was attenuated and abolished by NIM and DFU, respectively, while that caused by i.p. rmIL-1beta was converted into a T(c) fall by DFU. There were no differences in the responses to i.c.v. PGE2 among the WT and COX knockout mice. These results, therefore, further support the notion that the production of PGE2 in response to pyrogens is critically dependent on COX-2 expression.

Phospholipase C-beta4 is essential for the progression of the normal sleep sequence and ultradian body temperature rhythms in mice.

PubMed

Ikeda, Masayuki; Hirono, Moritoshi; Sugiyama, Takashi; Moriya, Takahiro; Ikeda-Sagara, Masami; Eguchi, Naomi; Urade, Yoshihiro; Yoshioka, Tohru

2009-11-09

THE SLEEP SEQUENCE: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the beta4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-beta4-deficient mutant (PLC-beta4-/-) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-beta4-/- mice, however. Therefore, we analyzed 24-h sleep electroencephalogram in PLC-beta4-/- mice. PLC-beta4-/- mice exhibited normal non-REM sleep both during the day and nighttime. PLC-beta4-/- mice, however, exhibited increased REM sleep during the night, their active period. Also, their sleep was fragmented with unusual wake-to-REM sleep transitions, both during the day and nighttime. In addition, PLC-beta4-/- mice reduced ultradian body temperature rhythms and elevated body temperatures during the daytime, but had normal homeothermal response to acute shifts in ambient temperatures (22 degrees C-4 degrees C). Within the most likely brain areas to produce these behavioral phenotypes, we found that, not orexin, but group-1 metabotropic glutamate receptor (mGluR)-mediated Ca(2+) mobilization was significantly reduced in the dorsal lateral geniculate nucleus (LGNd) of PLC-beta4-/- mice. Voltage clamp recordings revealed that group-1 mGluR-mediated currents in LGNd relay neurons (inward in wild-type mice) were outward in PLC-beta4-/- mice. These lines of evidence indicate that impaired LGNd relay, possibly mediated via group-1 mGluR, may underlie irregular sleep sequences and ultradian body temperature rhythms in PLC-beta4-/- mice.

Milk bioactive peptides and beta-casomorphins induce mucus release in rat jejunum.

PubMed

Trompette, Aurélien; Claustre, Jean; Caillon, Fabienne; Jourdan, Gérard; Chayvialle, Jean Alain; Plaisancié, Pascale

2003-11-01

Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and beta-casomorphin-7, a mu-opioid peptide generated in the intestine during bovine casein digestion, markedly induce mucus discharge. Because shorter mu-opioid peptides have been described, the effects of the opioid peptides in casein, beta-casomorphin-7, -6, -4, -4NH2 and -3, and of opioid neuropeptides met-enkephalin, dynorphin A and (D-Ala2,N-Me-Phe4,glycinol5)enkephalin (DAMGO) on intestinal mucus secretion were investigated. The experiments were conducted with isolated perfused rat jejunum. Mucus secretion under the influence of beta-casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of beta-casomorphin-7 (1.2 x 10(-4) mol/L) provoked a mucus discharge (500% of controls) that was inhibited by naloxone, a specific opiate receptor antagonist. Luminal beta-casomorphin-6, -4 and -4NH2 did not modify basal mucus secretion, whereas intra-arterial administration of beta-casomorphin-4 (1.2 x 10(-6) mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide beta-casomorphin-3 did not release mucus. Among the opioid neuropeptides, intra-arterial infusion of Met-enkephalin or dynorphin-A did not provoke mucus secretion. In contrast, beta-endorphin (1.2 x 10(-8) to 1.2 x 10(-6) mol/L) induced a dose-dependent release of mucus (maximal response at 500% of controls). DAMGO (1.2 x 10(-6) mol/L), a mu-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that mu-opioid neuropeptides, as well as beta-casomorphins after absorption, modulate intestinal mucus discharge. Milk opioid-derived peptides may thus be involved in defense against noxious agents and could have dietary and health applications.

Dynamical mechanisms for skeletal pattern formation in the vertebrate limb.

PubMed Central

Hentschel, H. G. E.; Glimm, Tilmann; Glazier, James A.; Newman, Stuart A.

2004-01-01

We describe a 'reactor-diffusion' mechanism for precartilage condensation based on recent experiments on chondrogenesis in the early vertebrate limb and additional hypotheses. Cellular differentiation of mesenchymal cells into subtypes with different fibroblast growth factor (FGF) receptors occurs in the presence of spatio-temporal variations of FGFs and transforming growth factor-betas (TGF-betas). One class of differentiated cells produces elevated quantities of the extracellular matrix protein fibronectin, which initiates adhesion-mediated preskeletal mesenchymal condensation. The same class of cells also produces an FGF-dependent laterally acting inhibitor that keeps condensations from expanding beyond a critical size. We show that this 'reactor-diffusion' mechanism leads naturally to patterning consistent with skeletal form, and describe simulations of spatio-temporal distribution of these differentiated cell types and the TGF-beta and inhibitor concentrations in the developing limb bud. PMID:15306292

Primate beta oscillations and rhythmic behaviors.

PubMed

Merchant, Hugo; Bartolo, Ramón

2018-03-01

The study of non-human primates in complex behaviors such as rhythm perception and entrainment is critical to understand the neurophysiological basis of human cognition. Next to reviewing the role of beta oscillations in human beat perception, here we discuss the role of primate putaminal oscillatory activity in the control of rhythmic movements that are guided by a sensory metronome or internally gated. The analysis of the local field potentials of the behaving macaques showed that gamma-oscillations reflect local computations associated with stimulus processing of the metronome, whereas beta-activity involves the entrainment of large putaminal circuits, probably in conjunction with other elements of cortico-basal ganglia-thalamo-cortical circuit, during internally driven rhythmic tapping. Thus, this review emphasizes the need of parametric neurophysiological observations in non-human primates that display a well-controlled behavior during high-level cognitive processes.

Disruption of estrogen receptor signaling enhances intestinal neoplasia in Apc(Min/+) mice.

PubMed

Cleveland, Alicia G; Oikarinen, Seija I; Bynoté, Kimberly K; Marttinen, Maija; Rafter, Joseph J; Gustafsson, Jan-Ake; Roy, Shyamal K; Pitot, Henry C; Korach, Kenneth S; Lubahn, Dennis B; Mutanen, Marja; Gould, Karen A

2009-09-01

Estrogen receptors (ERs) [ERalpha (Esr1) and ERbeta (Esr2)] are expressed in the human colon, but during the multistep process of colorectal carcinogenesis, expression of both ERalpha and ERbeta is lost, suggesting that loss of ER function might promote colorectal carcinogenesis. Through crosses between an ERalpha knockout and Apc(Min) mouse strains, we demonstrate that ERalpha deficiency is associated with a significant increase in intestinal tumor multiplicity, size and burden in Apc(Min/+) mice. Within the normal intestinal epithelium of Apc(Min/+) mice, ERalpha deficiency is associated with an accumulation of nuclear beta-catenin, an indicator of activation of the Wnt-beta-catenin-signaling pathway, which is known to play a critical role in intestinal cancers. Consistent with the hypothesis that ERalpha deficiency is associated with activation of Wnt-beta-catenin signaling, ERalpha deficiency in the intestinal epithelium of Apc(Min/+) mice also correlated with increased expression of Wnt-beta-catenin target genes. Through crosses between an ERbeta knockout and Apc(Min) mouse strains, we observed some evidence that ERbeta deficiency is associated with an increased incidence of colon tumors in Apc(Min/+) mice. This effect of ERbeta deficiency does not involve modulation of Wnt-beta-catenin signaling. Our studies suggest that ERalpha and ERbeta signaling modulate colorectal carcinogenesis, and ERalpha does so, at least in part, by regulating the activity of the Wnt-beta-catenin pathway.

Top-down beta oscillatory signaling conveys behavioral context in early visual cortex.

PubMed

Richter, Craig G; Coppola, Richard; Bressler, Steven L

2018-05-03

Top-down modulation of sensory processing is a critical neural mechanism subserving numerous important cognitive roles, one of which may be to inform lower-order sensory systems of the current 'task at hand' by conveying behavioral context to these systems. Accumulating evidence indicates that top-down cortical influences are carried by directed interareal synchronization of oscillatory neuronal populations, with recent results pointing to beta-frequency oscillations as particularly important for top-down processing. However, it remains to be determined if top-down beta-frequency oscillations indeed convey behavioral context. We measured spectral Granger Causality (sGC) using local field potentials recorded from microelectrodes chronically implanted in visual areas V1/V2, V4, and TEO of two rhesus macaque monkeys, and applied multivariate pattern analysis to the spatial patterns of top-down sGC. We decoded behavioral context by discriminating patterns of top-down (V4/TEO-to-V1/V2) beta-peak sGC for two different task rules governing correct responses to identical visual stimuli. The results indicate that top-down directed influences are carried to visual cortex by beta oscillations, and differentiate task demands even before visual stimulus processing. They suggest that top-down beta-frequency oscillatory processes coordinate processing of sensory information by conveying global knowledge states to early levels of the sensory cortical hierarchy independently of bottom-up stimulus-driven processing.

DNase I hypersensitivity and epsilon-globin transcriptional enhancement are separable in locus control region (LCR) HS1 mutant human beta-globin YAC transgenic mice.

PubMed

Shimotsuma, Motoshi; Okamura, Eiichi; Matsuzaki, Hitomi; Fukamizu, Akiyoshi; Tanimoto, Keiji

2010-05-07

Expression of the five beta-like globin genes (epsilon, Ggamma, Agamma, delta, beta) in the human beta-globin locus depends on enhancement by the locus control region, which consists of five DNase I hypersensitive sites (5'HS1 through 5'HS5). We report here a novel enhancer activity in 5'HS1 that appears to be potent in transfected K562 cells. Deletion analyses identified a core activating element that bound to GATA-1, and a two-nucleotide mutation that disrupted GATA-1 binding in vitro abrogated 5'HS1 enhancer activity in transfection experiments. To determine the in vivo role of this GATA site, we generated multiple lines of human beta-globin YAC transgenic mice bearing the same two-nucleotide mutation. In the mutant mice, epsilon-, but not gamma-globin, gene expression in primitive erythroid cells was severely attenuated, while adult beta-globin gene expression in definitive erythroid cells was unaffected. Interestingly, DNaseI hypersensitivity near the 5'HS1 mutant sequence was eliminated in definitive erythroid cells, whereas it was only mildly affected in primitive erythroid cells. We therefore conclude that, although the GATA site in 5'HS1 is critical for efficient epsilon-globin gene expression, hypersensitive site formation per se is independent of 5'HS1 function, if any, in definitive erythroid cells.

Using Brain Oscillations and Corticospinal Excitability to Understand and Predict Post-Stroke Motor Function.

PubMed

Thibaut, Aurore; Simis, Marcel; Battistella, Linamara Rizzo; Fanciullacci, Chiara; Bertolucci, Federica; Huerta-Gutierrez, Rodrigo; Chisari, Carmelo; Fregni, Felipe

2017-01-01

What determines motor recovery in stroke is still unknown and finding markers that could predict and improve stroke recovery is a challenge. In this study, we aimed at understanding the neural mechanisms of motor function recovery after stroke using neurophysiological markers by means of cortical excitability (transcranial magnetic stimulation-TMS) and brain oscillations (electroencephalography-EEG). In this cross-sectional study, 55 subjects with chronic stroke (62 ± 14 yo, 17 women, 32 ± 42 months post-stroke) were recruited in two sites. We analyzed TMS measures (i.e., motor threshold-MT-of the affected and unaffected sides) and EEG variables (i.e., power spectrum in different frequency bands and different brain regions of the affected and unaffected hemispheres) and their correlation with motor impairment as measured by Fugl-Meyer. Multiple univariate and multivariate linear regression analyses were performed to identify the predictors of good motor function. A significant interaction effect of MT in the affected hemisphere and power in beta bandwidth over the central region for both affected and unaffected hemispheres was found. We identified that motor function positively correlates with beta rhythm over the central region of the unaffected hemisphere, while it negatively correlates with beta rhythm in the affected hemisphere. Our results suggest that cortical activity in the affected and unaffected hemisphere measured by EEG provides new insights on the association between high-frequency rhythms and motor impairment, highlighting the role of an excess of beta in the affected central cortical region in poor motor function in stroke recovery.

Antipsychotics, Lithium, Benzodiazepines, Beta-Blockers.

ERIC Educational Resources Information Center

Karper, Laurence P.; And Others

1994-01-01

The psychopharmacologic treatment of aggression is a critical component of the treatment of psychiatric patients. The diagnostic assessment of aggressive patients is reviewed and relevant literature is presented to help clinicians select appropriate medication. Side-effects, dosages, and methods of administration are highlighted. (JPS)

Periodontal wound healing/regeneration following implantation of recombinant human growth/differentiation factor-5 in a beta-tricalcium phosphate carrier into one-wall intrabony defects in dogs.

PubMed

Lee, Jung-Seok; Wikesjö, Ulf M E; Jung, Ui-Won; Choi, Seong-Ho; Pippig, Susanne; Siedler, Michael; Kim, Chong-Kwan

2010-04-01

Recombinant human growth/differentiation factor-5 (rhGDF-5) is being evaluated as a candidate therapy in support of periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following the application of rhGDF-5 on a particulate beta-tricalcium phosphate (beta-TCP) carrier using an established defect model. Bilateral 4 x 5 mm (width x depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in 15 Beagle dogs. Unilateral defects in five animals received rhGDF-5/beta-TCP (Scil Technology GmbH); five animals received beta-TCP solo; and five animals served as sham-surgery controls. Contralateral sites received treatments reported elsewhere. The animals were sacrificed following an 8-week healing interval for histological examination. Clinical healing was generally uneventful. Sites implanted with rhGDF-5/beta-TCP exhibited greater enhanced cementum and bone formation compared with beta-TCP and sham-surgery controls; cementum regeneration averaged (+/- SD) 3.83 +/- 0.73 versus 1.65 +/- 0.82 and 2.48 +/- 1.28 mm for the controls (p<0.05). Corresponding values for bone regeneration height averaged 3.26 +/- 0.30 versus 1.70 +/- 0.66 and 1.68 +/- 0.49 mm (p<0.05), and bone area 10.45 +/- 2.26 versus 6.31 +/- 2.41 and 3.00 +/- 1.97 mm(2) (p<0.05). Cementum regeneration included cellular/acellular cementum with or without a functionally oriented periodontal ligament. A non-specific connective tissue attachment was evident in the sham-surgery control. Controls exhibited mostly woven bone with primary osteons, whereas rhGDF-5/beta-TCP sites showed a noticeable extent of lamellar bone. Sites receiving rhGDF-5/beta-TCP or beta-TCP showed some residual beta-TCP granules apparently undergoing biodegradation without obvious differences between the sites. Sites receiving beta-TCP alone commonly showed residual beta-TCP granules sequestered in the connective tissue or fibrovascular marrow. rhGDF-5/beta-TCP has a greater potential to support the regeneration of the periodontal attachment. Long-term studies are necessary to confirm the uneventful maturation of the regenerated tissues.

Validating the Kinematic Wave Approach for Rapid Soil Erosion Assessment and Improved BMP Site Selection to Enhance Training Land Sustainability

DTIC Science & Technology

2014-02-01

installation based on a Euclidean distance allocation and assigned that installation’s threshold values. The second approach used a thin - plate spline ...installation critical nLS+ thresholds involved spatial interpolation. A thin - plate spline radial basis functions (RBF) was selected as the...the interpolation of installation results using a thin - plate spline radial basis function technique. 6.5 OBJECTIVE #5: DEVELOP AND

(Re)Conceptualizing Higher Education in Post-Disaster Contexts: A Processual Analysis of Diaspora Engagement in Haiti's Reconstruction

ERIC Educational Resources Information Center

Cela Hamm, Toni

2016-01-01

In post-disaster and post-conflict societies, critical threshold events trigger or intensify diaspora mobilization and engagement in their homelands. Taking the 2010 earthquake as a "critical event" that has transformed the course of Haitian society, this study builds on existing research on diaspora influence on homeland development by…

Active Learning and Threshold Concepts in Multiple Testing That Can Further Develop Student Critical Statistical Thinking

ERIC Educational Resources Information Center

White, Desley

2015-01-01

Two practical activities are described, which aim to support critical thinking about statistics as they concern multiple outcomes testing. Formulae are presented in Microsoft Excel spreadsheets, which are used to calculate the inflation of error associated with the quantity of tests performed. This is followed by a decision-making exercise, where…

Association of ambient particulate matter with heart failure incidence and all-cause readmissions in Tasmania: an observational study.

PubMed

Huynh, Quan L; Blizzard, Christopher Leigh; Marwick, Thomas H; Negishi, Kazuaki

2018-05-10

We sought to investigate the relationship between air quality and heart failure (HF) incidence and rehospitalisation to elucidate whether there is a threshold in this relationship and whether this relationship differs for HF incidence and rehospitalisation. This retrospective observational study was performed in an Australian state-wide setting, where air pollution is mainly associated with wood-burning for winter heating. Data included all 1246 patients with a first-ever HF hospitalisation and their 3011 subsequent all-cause readmissions during 2009-2012. Daily particulate matter <2.5 µm (PM 2.5 ), temperature, relative humidity and influenza infection were recorded. Poisson regression was used, with adjustment for time trend, public and school holiday and day of week. Tasmania has excellent air quality (median PM 2.5 =2.9 µg/m 3 (IQR: 1.8-6.0)). Greater HF incidences and readmissions occurred in winter than in other seasons (p<0.001). PM 2.5 was detrimentally associated with HF incidence (risk ratio (RR)=1.29 (1.15-1.42)) and weakly so with readmission (RR=1.07 (1.02-1.17)), with 1 day time lag. In multivariable analyses, PM 2.5 significantly predicted HF incidence (RR=1.12 (1.01-1.24)) but not readmission (RR=0.96 (0.89-1.04)). HF incidence was similarly low when PM <4 µg/m 3 and only started to rise when PM 2.5 ≥4 µg/m 3 . Stratified analyses showed that PM 2.5 was associated with readmissions among patients not taking beta-blockers but not among those taking beta-blockers (p interaction =0.011). PM 2.5 predicted HF incidence, independent of other environmental factors. A possible threshold of PM 2.5 =4 µg/m 3 is far below the daily Australian national standard of 25 µg/m 3 . Our data suggest that beta-blockers might play a role in preventing adverse association between air pollution and patients with HF. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Glutamate-induced excitation and sensitization of nociceptors in rat glabrous skin.

PubMed

Du, J; Koltzenburg, M; Carlton, S M

2001-01-01

Anatomical studies demonstrate the presence of glutamate receptors on unmyelinated axons in peripheral cutaneous nerves. Pharmacological studies show that intraplantar injection of glutamate or glutamate agonists in the glabrous skin results in nociceptive behaviors. The present study describes a novel in vitro skin-nerve preparation using the glabrous skin from the rat hindpaw. In the first series of experiments, recordings were obtained from 141 fibers that responded to a strong mechanical search stimulus. Based on their conduction velocity they were classified as C (27%), A delta (28%) and A beta (45%) fibers. The C and A delta fibers typically exhibited sustained firing during suprathreshold mechanical stimuli whereas both rapidly (66%) and slowly (34%) adapting responses were obtained from A beta fibers. Noxious heat excited 46% of the C fibers but only 12% of the A delta units. In another series of experiments application of an ascending series of glutamate concentrations (10, 100, 300, and 1000 microM) to A delta (n=14) and C (n=19) nociceptors resulted in a significant excitation of 43% (6/14) A delta fibers and 68% (13/19) C fibers. At these concentrations, there was no excitation of A beta units (n=13). Superfusion of the receptive fields of either mechanoheat-sensitive A (AMH, n=10) or C fibers (CMH, n=12) for 2 min with 300 microM glutamate resulted in sensitization of 90% (9/10) AMH and 92% (11/12) CMH fibers to subsequent thermal stimulation. This was evidenced by a significant (1) decrease in thermal threshold for activation, (2) increase in discharge rate, and (3) increase in peak instantaneous frequencies during the second heat trial. Glutamate-induced sensitization to heat occurred in the absence of either a glutamate-induced excitation or an initial heat response. Exposure of A delta or C fibers to glutamate did not result in a decrease in von Frey thresholds. These data provide a physiological basis for the nociceptive behaviors that arise following intraplantar injection of glutamate or glutamate agonists. Furthermore, demonstration of glutamate-induced excitation and heat sensitization of nociceptors indicates that local or topical administration of glutamate receptor antagonists may have therapeutic potential for the treatment of pain.

RACK1 binds to Smad3 to modulate transforming growth factor-beta1-stimulated alpha2(I) collagen transcription in renal tubular epithelial cells.

PubMed

Okano, Kazuhiro; Schnaper, H William; Bomsztyk, Karol; Hayashida, Tomoko

2006-09-08

Although it is clear that transforming growth factor-beta1 (TGF-beta1) is critical for renal fibrogenesis, the complexity of the involved mechanisms is increasingly apparent. TGF-beta1 stimulates phosphorylation of Smad2/3 and activates other signaling molecules as well. The molecular link between these other kinases and Smads is not known. We sought new binding partners for Smad3 in renal cells and identified receptor for activated protein kinase C 1 (RACK1) as a novel binding partner of Smad3. The linker region of Smad3 and the tryptophan-aspartic acid repeat 6 and 7 of RACK1 are sufficient for the association. RACK1 also interacts with Smad3 in the human kidney epithelial cell line, HKC. Silencing RACK1 increases transcriptional activity of TGF-beta1-responsive promoter sequences of the Smad binding element (SBE), p3TP-Lux, and alpha2(I) collagen. Conversely, overexpressed RACK1 negatively modulates alpha2(I) collagen transcriptional activity in TGF-beta1-stimulated cells. RACK1 did not affect phosphorylation of Smad3 at the C terminus or in the linker region. However, RACK1 reduced direct binding of Smad3 to the SBE motif. Mutating a RACK1 tyrosine at residue 246, but not at 228, decreased the inhibitory effect of RACK1 on both alpha2(I) collagen promoter activity and Smad binding to SBE induced by TGF-beta1. These results suggest that RACK1 modulates transcription of alpha2(I) collagen by TGF-beta1 through interference with Smad3 binding to the gene promoter.

The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus

PubMed Central

Gerber, Philipp A.

2017-01-01

Abstract Significance: Metabolic syndrome is a frequent precursor of type 2 diabetes mellitus (T2D), a disease that currently affects ∼8% of the adult population worldwide. Pancreatic beta-cell dysfunction and loss are central to the disease process, although understanding of the underlying molecular mechanisms is still fragmentary. Recent Advances: Oversupply of nutrients, including glucose and fatty acids, and the subsequent overstimulation of beta cells, are believed to be an important contributor to insulin secretory failure in T2D. Hypoxia has also recently been implicated in beta-cell damage. Accumulating evidence points to a role for oxidative stress in both processes. Although the production of reactive oxygen species (ROS) results from enhanced mitochondrial respiration during stimulation with glucose and other fuels, the expression of antioxidant defense genes is unusually low (or disallowed) in beta cells. Critical Issues: Not all subjects with metabolic syndrome and hyperglycemia go on to develop full-blown diabetes, implying an important role in disease risk for gene–environment interactions. Possession of common risk alleles at the SLC30A8 locus, encoding the beta-cell granule zinc transporter ZnT8, may affect cytosolic Zn2+ concentrations and thus susceptibility to hypoxia and oxidative stress. Future Directions: Loss of normal beta-cell function, rather than total mass, is increasingly considered to be the major driver for impaired insulin secretion in diabetes. Better understanding of the role of oxidative changes, its modulation by genes involved in disease risk, and effects on beta-cell identity may facilitate the development of new therapeutic strategies to this disease. Antioxid. Redox Signal. 26, 501–518. PMID:27225690

A beta-l-Arabinopyranosidase from Streptomyces avermitilis is a novel member of glycoside hydrolase family 27.

PubMed

Ichinose, Hitomi; Fujimoto, Zui; Honda, Mariko; Harazono, Koichi; Nishimoto, Yukifumi; Uzura, Atsuko; Kaneko, Satoshi

2009-09-11

Arabinogalactan proteins (AGPs) are a family of plant cell surface proteoglycans and are considered to be involved in plant growth and development. Because AGPs are very complex molecules, glycoside hydrolases capable of degrading AGPs are powerful tools for analyses of the AGPs. We previously reported such enzymes from Streptomyces avermitilis. Recently, a beta-l-arabinopyranosidase was purified from the culture supernatant of the bacterium, and its corresponding gene was identified. The primary structure of the protein revealed that the catalytic module was highly similar to that of glycoside hydrolase family 27 (GH27) alpha-d-galactosidases. The recombinant protein was successfully expressed as a secreted 64-kDa protein using a Streptomyces expression system. The specific activity toward p-nitrophenyl-beta-l-arabinopyranoside was 18 micromol of arabinose/min/mg, which was 67 times higher than that toward p- nitrophenyl-alpha-d-galactopyranoside. The enzyme could remove 0.1 and 45% l-arabinose from gum arabic or larch arabinogalactan, respectively. X-ray crystallographic analysis reveals that the protein had a GH27 catalytic domain, an antiparallel beta-domain containing Greek key motifs, another antiparallel beta-domain forming a jellyroll structure, and a carbohydrate-binding module family 13 domain. Comparison of the structure of this protein with that of alpha-d-galactosidase showed a single amino acid substitution (aspartic acid to glutamic acid) in the catalytic pocket of beta-l-arabinopyranosidase, and a space for the hydroxymethyl group on the C-5 carbon of d-galactose bound to alpha-galactosidase was changed in beta-l-arabinopyranosidase. Mutagenesis study revealed that the residue is critical for modulating the enzyme activity. This is the first report in which beta-l-arabinopyranosidase is classified as a new member of the GH27 family.

The effect of narrow-band noise maskers on increment detection1

PubMed Central

Messersmith, Jessica J.; Patra, Harisadhan; Jesteadt, Walt

2010-01-01

It is often assumed that listeners detect an increment in the intensity of a pure tone by detecting an increase in the energy falling within the critical band centered on the signal frequency. A noise masker can be used to limit the use of signal energy falling outside of the critical band, but facets of the noise may impact increment detection beyond this intended purpose. The current study evaluated the impact of envelope fluctuation in a noise masker on thresholds for detection of an increment. Thresholds were obtained for detection of an increment in the intensity of a 0.25- or 4-kHz pedestal in quiet and in the presence of noise of varying bandwidth. Results indicate that thresholds for detection of an increment in the intensity of a pure tone increase with increasing bandwidth for an on-frequency noise masker, but are unchanged by an off-frequency noise masker. Neither a model that includes a modulation-filter-bank analysis of envelope modulation nor a model based on discrimination of spectral patterns can account for all aspects of the observed data. PMID:21110593

Percolation Thresholds in Angular Grain media: Drude Directed Infiltration

NASA Astrophysics Data System (ADS)

Priour, Donald

Pores in many realistic systems are not well delineated channels, but are void spaces among grains impermeable to charge or fluid flow which comprise the medium. Sparse grain concentrations lead to permeable systems, while concentrations in excess of a critical density block bulk fluid flow. We calculate percolation thresholds in porous materials made up of randomly placed (and oriented) disks, tetrahedrons, and cubes. To determine if randomly generated finite system samples are permeable, we deploy virtual tracer particles which are scattered (e.g. specularly) by collisions with impenetrable angular grains. We hasten the rate of exploration (which would otherwise scale as ncoll1 / 2 where ncoll is the number of collisions with grains if the tracers followed linear trajectories) by considering the tracer particles to be charged in conjunction with a randomly directed uniform electric field. As in the Drude treatment, where a succession of many scattering events leads to a constant drift velocity, tracer displacements on average grow linearly in ncoll. By averaging over many disorder realizations for a variety of systems sizes, we calculate the percolation threshold and critical exponent which characterize the phase transition.

L to H mode transition: Parametric dependencies of the temperature threshold

DOE PAGES

Bourdelle, C.; Chone, L.; Fedorczak, N.; ...

2015-06-15

The L to H mode transition occurs at a critical power which depends on various parameters, such as the magnetic field, the density, etc. Experimental evidence on various tokamaks (JET, ASDEX-Upgrade, DIII-D, Alcator C-Mod) points towards the existence of a critical temperature characterizing the transition. This criterion for the L-H transition is local and is therefore easier to be compared to theoretical approaches. In order to shed light on the mechanisms of the transition, simple theoretical ideas are used to derive a temperature threshold (T th). They are based on the stabilization of the underlying turbulence by a mean radialmore » electric field shear. The nature of the turbulence varies as the collisionality decreases, from resistive ballooning modes to ion temperature gradient and trapped electron modes. The obtained parametric dependencies of the derived T th are tested versus magnetic field, density, effective charge. Furthermore, various robust experimental observations are reproduced, in particular T th increases with magnetic field B and increases with density below the density roll-over observed on the power threshold.« less

Experimental evidence of the vapor recoil mechanism in the boiling crisis.

PubMed

Nikolayev, V S; Chatain, D; Garrabos, Y; Beysens, D

2006-11-03

Boiling crisis experiments are carried out in the vicinity of the liquid-gas critical point of H2. A magnetic gravity compensation setup is used to enable nucleate boiling at near critical pressure. The measurements of the critical heat flux that defines the threshold for the boiling crisis are carried out as a function of the distance from the critical point. The obtained power law behavior and the boiling crisis dynamics agree with the predictions of the vapor recoil mechanism and disagree with the classical vapor column mechanism.

Evaluation of the Orogenic Belt Hypothesis for the Formation of Thaumasia, Mars

NASA Astrophysics Data System (ADS)

Nahm, A. L.; Schultz, R. A.

2008-12-01

The Thaumasia Highlands (TH) and Solis Planum are two of the best-known examples of compressional tectonics on Mars. The TH is a region of high topography located in the southern portion of the Tharsis Province, Mars. Solis Planum is located in eastern Thaumasia. Two hypotheses for the formation of this region have been suggested: sliding on a weak horizon or thrusting analogous to orogenic wedges on Earth. Both hypotheses require a shallowly dipping to sub-horizontal weak horizon below Thaumasia. Wrinkle ridges in Solis Planum are also inferred to sole into a décollement. If Thaumasia formed by thrusting related to sliding on a décollement, then certain conditions must be met as in critical taper wedge mechanics (CTWM) theory. If the angle between the surface slope and the basal décollement is less than predicted by the critical taper equation, the 'subcritical' wedge will deform internally until critical taper is achieved. Once the critical taper has been achieved, internal deformation ceases and the wedge will slide along its base. Formation of orogenic belts on Earth (such as the Central Mountains in Taiwan) can be described using CTWM. This method is applied here to the Thaumasia region on Mars. The surface slope (alpha) was measured in three locations: Syria Planum-Thaumasia margin, Solis Planum, and the TH. Topographic slopes were compared to the results from the critical taper equation. Because the dip of the basal décollement (beta) cannot be measured directly as on Earth, the dip angle was varied at 0 - 10 degrees; these values span the range of likely values based on terrestrial wedges. Pore fluid pressure (lambda) was varied between 0 (dry) and 0.9 (overpressured); these values span the full range of this important unknown parameter. Material properties, such as the coefficients of internal friction and of the basal décollement, were varied using reasonable values. Preliminary results show that for both reasonable (such as lambda = 0, mu b = 0.85, beta = 0 deg) and extreme (such as lambda = 0.9, mu b = 0.1, beta greater than 0 deg) values of the parameters for Mars, the predicted critical taper angle was typically lower than the measured slope, rendering the orogenic belt hypothesis for the formation of the TH invalid. Comparable analysis of Solis Planum shows it also lacks a décollement.

The Effect of Fin Pitch on Fluid Elastic Instability of Tube Arrays Subjected to Cross Flow of Water

NASA Astrophysics Data System (ADS)

Desai, Sandeep Rangrao; Pavitran, Sampat

2018-02-01

Failure of tubes in shell and tube exchangers is attributed to flow induced vibrations of such tubes. There are different excitations mechanisms due to which flow induced vibration occurs and among such mechanisms, fluid elastic instability is the most prominent one as it causes the most violent vibrations and may lead to rapid tube failures within short time. Fluid elastic instability is the fluid-structure interaction phenomenon which occurs when energy input by the fluid force exceeds energy expended in damping. This point is referred as instability threshold and corresponding velocity is referred as critical velocity. Once flow velocity exceeds critical flow velocity, the vibration amplitude increases very rapidly with flow velocity. An experimental program is carried out to determine the critical velocity at instability for plain and finned tube arrays subjected to cross flow of water. The tube array geometry is parallel triangular with cantilever end condition and pitch ratios considered are 2.6 and 2.1. The objective of research is to determine the effect of increase in pitch ratio on instability threshold for plain tube arrays and to assess the effect of addition of fins as well as increase in fin density on instability threshold for finned tube arrays. Plain tube array with two different pitch ratios; 2.1 and 2.6 and finned tube arrays with same pitch ratio; 2.6 but with two different fin pitches; such as fine (10 fpi) and coarse (4 fpi) are considered for the experimentation. Connors' equation that relates critical velocity at instability to different parameters, on which instability depends, has been used as the basis for analysis and the concept of effective diameter is used for the present investigation. The modal parameters are first suitably modified using natural frequency reduction setup that is already designed and developed to reduce natural frequency and hence to achieve experimental simulation of fluid elastic instability within the limited flow capacity of the pump. The tests are carried out first on plain tube arrays to establish the same as the datum case and results are compared to known results of plain tube arrays and hence the quality of the test rig is also assessed. The fluid elastic vibration tests are then carried out on finned tube arrays with coarse and fine fin pitches and effects of fins and fin pitch on instability threshold are shown. The vibration response of the tube is recorded for each gradually increasing flow rates of water till instability point is reached. The parameters at the instability are then presented in terms of dimensionless parameters to compare them with published results. It is concluded that, arrays with higher pitch ratios are unstable at comparatively higher flow velocities and instability threshold for finned tube arrays is delayed due to addition of the fins. Further, it is concluded that, instability threshold for finned tube arrays with fine fin pitch is delayed compared to coarse fin pitch and hence for increased fin density, instability threshold is delayed. The experimental results in terms of critical velocities obtained for different tube arrays subjected to water cross flow will serve as the base flow rates for air-water cross flow experiments to be conducted in the next phase.

Normalizing rainfall/debris-flow thresholds along the U.S. Pacific coast for long-term variations in precipitation climate

USGS Publications Warehouse

Wilson, Raymond C.

1997-01-01

Broad-scale variations in long-term precipitation climate may influence rainfall/debris-flow threshold values along the U.S. Pacific coast, where both the mean annual precipitation (MAP) and the number of rainfall days (#RDs) are controlled by topography, distance from the coastline, and geographic latitude. Previous authors have proposed that rainfall thresholds are directly proportional to MAP, but this appears to hold only within limited areas (< 1?? latitude), where rainfall frequency (#RDs) is nearly constant. MAP-normalized thresholds underestimate the critical rainfall when applied to areas to the south, where the #RDs decrease, and overestimate threshold rainfall when applied to areas to the north, where the #RDs increase. For normalization between climates where both MAP and #RDs vary significantly, thresholds may best be described as multiples of the rainy-day normal, RDN = MAP/#RDs. Using data from several storms that triggered significant debris-flow activity in southern California, the San Francisco Bay region, and the Pacific Northwest, peak 24-hour rainfalls were plotted against RDN values, displaying a linear relationship with a lower bound at about 14 RDN. RDN ratios in this range may provide a threshold for broad-scale regional forecasting of debris-flow activity.

Redefining the Speed Limit of Phase Change Memory Revealed by Time-resolved Steep Threshold-Switching Dynamics of AgInSbTe Devices

NASA Astrophysics Data System (ADS)

Shukla, Krishna Dayal; Saxena, Nishant; Durai, Suresh; Manivannan, Anbarasu

2016-11-01

Although phase-change memory (PCM) offers promising features for a ‘universal memory’ owing to high-speed and non-volatility, achieving fast electrical switching remains a key challenge. In this work, a correlation between the rate of applied voltage and the dynamics of threshold-switching is investigated at picosecond-timescale. A distinct characteristic feature of enabling a rapid threshold-switching at a critical voltage known as the threshold voltage as validated by an instantaneous response of steep current rise from an amorphous off to on state is achieved within 250 picoseconds and this is followed by a slower current rise leading to crystallization. Also, we demonstrate that the extraordinary nature of threshold-switching dynamics in AgInSbTe cells is independent to the rate of applied voltage unlike other chalcogenide-based phase change materials exhibiting the voltage dependent transient switching characteristics. Furthermore, numerical solutions of time-dependent conduction process validate the experimental results, which reveal the electronic nature of threshold-switching. These findings of steep threshold-switching of ‘sub-50 ps delay time’, opens up a new way for achieving high-speed non-volatile memory for mainstream computing.

VizieR Online Data Catalog: Statistical test on binary stars non-coevality (Valle+, 2016)

NASA Astrophysics Data System (ADS)

Valle, G.; Dell'Omodarme, M.; Valle, G.; Prada Moroni, P. G.; Degl'Innocenti, S.

2016-01-01

The table contains the W0.95 critical values, for the 1087 binary systems considered in the paper. Tha table also lists the parameters of the beta distributions approximating the empirical W distributions. (1 data file).

Percolation of disordered jammed sphere packings

NASA Astrophysics Data System (ADS)

Ziff, Robert M.; Torquato, Salvatore

2017-02-01

We determine the site and bond percolation thresholds for a system of disordered jammed sphere packings in the maximally random jammed state, generated by the Torquato-Jiao algorithm. For the site threshold, which gives the fraction of conducting versus non-conducting spheres necessary for percolation, we find {{p}\\text{c}}=0.3116(3) , consistent with the 1979 value of Powell 0.310(5) and identical within errors to the threshold for the simple-cubic lattice, 0.311 608, which shares the same average coordination number of 6. In terms of the volume fraction ϕ, the threshold corresponds to a critical value {φ\\text{c}}=0.199 . For the bond threshold, which apparently was not measured before, we find {{p}\\text{c}}=0.2424(3) . To find these thresholds, we considered two shape-dependent universal ratios involving the size of the largest cluster, fluctuations in that size, and the second moment of the size distribution; we confirmed the ratios’ universality by also studying the simple-cubic lattice with a similar cubic boundary. The results are applicable to many problems including conductivity in random mixtures, glass formation, and drug loading in pharmaceutical tablets.

Mitochondrial threshold effects.

PubMed Central

Rossignol, Rodrigue; Faustin, Benjamin; Rocher, Christophe; Malgat, Monique; Mazat, Jean-Pierre; Letellier, Thierry

2003-01-01

The study of mitochondrial diseases has revealed dramatic variability in the phenotypic presentation of mitochondrial genetic defects. To attempt to understand this variability, different authors have studied energy metabolism in transmitochondrial cell lines carrying different proportions of various pathogenic mutations in their mitochondrial DNA. The same kinds of experiments have been performed on isolated mitochondria and on tissue biopsies taken from patients with mitochondrial diseases. The results have shown that, in most cases, phenotypic manifestation of the genetic defect occurs only when a threshold level is exceeded, and this phenomenon has been named the 'phenotypic threshold effect'. Subsequently, several authors showed that it was possible to inhibit considerably the activity of a respiratory chain complex, up to a critical value, without affecting the rate of mitochondrial respiration or ATP synthesis. This phenomenon was called the 'biochemical threshold effect'. More recently, quantitative analysis of the effects of various mutations in mitochondrial DNA on the rate of mitochondrial protein synthesis has revealed the existence of a 'translational threshold effect'. In this review these different mitochondrial threshold effects are discussed, along with their molecular bases and the roles that they play in the presentation of mitochondrial diseases. PMID:12467494

The effect of various opiate receptor agonists on the seizure threshold in the rat. Is dynorphin an endogenous anticonvulsant?

PubMed

Przewłocka, B; Stala, L; Lasoń, W; Przewłocki, R

1983-01-01

The effects of various opiate receptor agonists on the seizure threshold after an intravenous infusion of pentylenetetrazol were investigated in rats. The mu- and epsilon-receptor agonists, morphine (20-40 micrograms) and beta-endorphin (5-10 micrograms) show proconvulsant properties towards clonic and tonic seizures. The delta-receptor agonist (D-Ala2,D-Leu5-enkephalin, DADL 5-40 micrograms) and alpha-neoendorphin (20-40 micrograms) show pro- and anticonvulsant properties towards clonic and tonic seizures, respectively. Anticonvulsant properties of DADL are possibly due to its action on the spinal cord, since after the intrathecal injection this effect is still observed. Similarities between DADL and alpha-neoendorphin suggest that they may act through the same receptor. The kappa-receptor agonist dynorphin A (5-20 micrograms) and its degradation-resistant analogue D-Arg-dynorphin1-13 (10 micrograms) show significant anticonvulsant properties. Our present results suggest that the kappa-receptor agonist dynorphin may act physiologically as an endogenous anticonvulsant, in contrast to other opioid peptides.

Improved Intratumoral Oxygenation Through Vascular Normalization Increases Glioma Sensitivity to Ionizing Radiation

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

McGee, Mackenzie C.; Hamner, J. Blair; Williams, Regan F.

2010-04-15

Purpose: Ionizing radiation, an important component of glioma therapy, is critically dependent on tumor oxygenation. However, gliomas are notable for areas of necrosis and hypoxia, which foster radioresistance. We hypothesized that pharmacologic manipulation of the typically dysfunctional tumor vasculature would improve intratumoral oxygenation and, thus, the antiglioma efficacy of ionizing radiation. Methods and Materials: Orthotopic U87 xenografts were treated with either continuous interferon-beta (IFN-beta) or bevacizumab, alone, or combined with cranial irradiation (RT). Tumor growth was assessed by quantitative bioluminescence imaging; the tumor vasculature using immunohistochemical staining, and tumor oxygenation using hypoxyprobe staining. Results: Both IFN-beta and bevaziumab profoundly affectedmore » the tumor vasculature, albeit with different cellular phenotypes. IFN-beta caused a doubling in the percentage of area of perivascular cell staining, and bevacizumab caused a rapid decrease in the percentage of area of endothelial cell staining. However, both agents increased intratumoral oxygenation, although with bevacizumab, the effect was transient, being lost by 5 days. Administration of IFN-beta or bevacizumab before RT was significantly more effective than any of the three modalities as monotherapy or when RT was administered concomitantly with IFN-beta or bevacizumab or 5 days after bevacizumab. Conclusion: Bevacizumab and continuous delivery of IFN-beta each induced significant changes in glioma vascular physiology, improving intratumoral oxygenation and enhancing the antitumor activity of ionizing radiation. Additional investigation into the use and timing of these and other agents that modify the vascular phenotype, combined with RT, is warranted to optimize cytotoxic activity.« less

Oxidized low-density lipoprotein acts synergistically with beta-glycerophosphate to induce osteoblast differentiation in primary cultures of vascular smooth muscle cells.

PubMed

Bear, Mackenzie; Butcher, Martin; Shaughnessy, Stephen G

2008-09-01

Previous studies have localized osteoblast specific markers to sites of calcified atherosclerotic lesions. We therefore decided to use an established in vitro model of vascular calcification in order to confirm earlier reports of oxidized low-density lipoprotein (oxLDL) promoting the osteogenic differentiation of vascular smooth muscle cells. Treatment of primary bovine aortic smooth muscle cells (BASMCs) with beta-glycerophosphate was found to induce a time-dependent increase in osteoblast differentiation. In contrast, no effect was seen when BASMCs were cultured in the presence of oxLDL alone. However, when the BASMCs were cultured in the presence of both beta-glycerophosphate and oxLDL, beta-glycerophosphate's ability to induce osteoblast differentiation was significantly enhanced. In an attempt to resolve the mechanism by which this effect was occurring, we examined the effect of beta-glycerophosphate and oxLDL on several pathways known to be critical to the differentiation of osteoblasts. Surprisingly, beta-glycerophosphate alone was found to enhance Osterix (Osx) expression by inducing both Smad 1/5/8 activation and Runx2 expression. In contrast, oxLDL did not affect either Smad 1/5/8 activation or Runx2 activation but rather, it enhanced both beta-glycerophosphate-induced Osx expression and osteoblast differentiation in an extracellular signal-regulated kinase 1 and 2 (Erk 1 and 2) -dependent manner. When taken together, these findings suggest a plausible mechanism by which oxLDL may promote osteogenic differentiation and vascular calcification in vivo. J. Cell. Biochem. 105: 185-193, 2008. (c) 2008 Wiley-Liss, Inc. (c) 2008 Wiley-Liss, Inc.

Critical loads of nitrogen deposition and critical levels of atmospheric ammonia for semi-natural Mediterranean evergreen woodlands

NASA Astrophysics Data System (ADS)

Pinho, P.; Theobald, M. R.; Dias, T.; Tang, Y. S.; Cruz, C.; Martins-Loução, M. A.; Máguas, C.; Sutton, M.; Branquinho, C.

2012-03-01

Nitrogen (N) has emerged in recent years as a key factor associated with global changes, with impacts on biodiversity, ecosystems functioning and human health. In order to ameliorate the effects of excessive N, safety thresholds such as critical loads (deposition fluxes) and levels (concentrations) can be established. Few studies have assessed these thresholds for semi-natural Mediterranean ecosystems. Our objective was therefore to determine the critical loads of N deposition and long-term critical levels of atmospheric ammonia for semi-natural Mediterranean evergreen woodlands. We have considered changes in epiphytic lichen communities, one of the most sensitive comunity indicators of excessive N in the atmosphere. Based on a classification of lichen species according to their tolerance to N we grouped species into response functional groups, which we used as a tool to determine the critical loads and levels. This was done for a Mediterranean climate in evergreen cork-oak woodlands, based on the relation between lichen functional diversity and modelled N deposition for critical loads and measured annual atmospheric ammonia concentrations for critical levels, evaluated downwind from a reduced N source (a cattle barn). Modelling the highly significant relationship between lichen functional groups and annual atmospheric ammonia concentration showed the critical level to be below 1.9 μg m-3, in agreement with recent studies for other ecosystems. Modelling the highly significant relationship between lichen functional groups and N deposition showed that the critical load was lower than 26 kg (N) ha-1 yr-1, which is within the upper range established for other semi-natural ecosystems. Taking into account the high sensitivity of lichen communities to excessive N, these values should aid development of policies to protect Mediterranean woodlands from the initial effects of excessive N.

Pulse oximetry findings in newborns with antenatally diagnosed congenital heart disease.

PubMed

Mawson, Isabel E; Babu, Pratusha L; Simpson, John M; Fox, Grenville F

2018-05-01

A retrospective review of admission preductal oxygen saturations of neonates with antenatally diagnosed critical congenital heart disease (CCHD) was performed to investigate the differences in newborn pulse oximetry (Pulsox) by specific CCHD diagnosis. Saturations were recorded at median of < 1 h (range < 1-9 h) after delivery. Data was stratified by CCHD diagnosis and analysed according to the three different admission Pulsox thresholds, ≤ 90, ≤ 92 and ≤ 95%. Of the 276 neonates studied, 208 were clinically well at admission, with no co-morbidities, gestation > 34 weeks and birth weight > 1.8 kg. A statistically significant increase in the proportion with low admission saturations was seen using ≤ 95% saturation threshold (72% (95% CI 66-78)) compared to ≤ 92% (52% (95% CI 46-59)) and ≤ 90% (46% (95% CI 39-52)). Sub-group analysis found the proportion of neonates with low saturations varied according to the specific CCHD diagnosis with only 20-42% of neonates with aortic stenosis, coarctation of the aorta and pulmonary stenosis having saturations ≤ 95%. The proportion of neonates with low admission oxygen saturation varied by CCHD diagnosis with those without critically reduced pulmonary blood flow not having low admission saturations, in general, even using the ≤ 95% threshold which had the highest proportions of abnormal saturations. This data may assist developing Pulsox screening policies. What is Known: • The addition of pulse oximetry (Pulsox) screening to the routine newborn examination increases the sensitivity of CCHD detection. Pulsox screening is also highly specific for CCHD in asymptomatic neonates, with low false-positive rates. • Early diagnosis of CCHD improves patient outcomes in relation to both morbidity and mortality. What is New: • The proportion of affected infants with an abnormal Pulsox result varies by CCHD diagnosis and screening threshold. In our study using the ≤ 95% threshold gave the highest proportion of neonates with abnormal saturations at admission. • In general, Pulsox yield of abnormal results is low for CCHD diagnoses not associated with critically reduced pulmonary blood flow; however, increasing the Pulsox threshold increased the proportion of infants with an abnormal result.

Thrust augmentation options for the Beta 2 two-stage-to-orbit vehicle

NASA Technical Reports Server (NTRS)

Snyder, Christopher A.

1993-01-01

NASA LeRC is continuing to study propulsion concepts for a horizontal takeoff and landing, fully reusable, two-stage-to-orbit vehicle. This will be capable of launching and returning a 10,000 pound payload to a 100 nautical mile polar orbit using low-risk technology. The vehicle, Beta 2, is a derivative of the USAF/Boeing Beta vehicle which was designed to deliver a 50,000 pound payload to a similar orbit. Beta 2 stages at Mach 6.5 and about 100,000 ft altitude. The propulsion system for the booster is an over/under turbine bypass engine/ramjet configuration. In this paper, several options for thrust augmentation were studied in order to improve the performance of this engine where there was a critical need. Options studies were turbine engine overspeed in the transonic region, water injection at a various turbine engine locations also during the transonic region, and water injection at the turbine engine face during high speed operation. The methodology, constraints, propulsion performance, and mission study results are presented.

Production and installation of the LHC low-beta triplets

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

Feher, S.; Bossert, R.; DiMarco, J.

2005-09-01

The LHC performance depends critically on the low-{beta}, triplets, located on either side of the four interaction points. Each triplet consists of four superconducting quadrupole magnets, which must operate reliably at up to 215 T/m, sustain extremely high heat loads and have an excellent field quality. A collaboration of CERN, Fermilab and KEK was formed in 1996 to design and build the triplet systems, and after nine years of joint effort the production has been completed in 2005. We retrace the main events of the project and present the design features and performance of the low-{beta} quadrupoles, built by KEKmore » and Fermilab, as well as of other vital elements of the triplet. The tunnel installation of the first triplet and plans for commissioning in the LHC are also presented. Apart from the excellent technical results, the construction of the LHC low-{beta} triplets has been a highly enriching experience combining harmoniously the different competences and approaches to engineering in a style reminiscent of high energy physics experiment collaborations, and rarely before achieved in construction of an accelerator.« less

The influence of major dietary fatty acids on insulin secretion and action.

PubMed

López, Sergio; Bermúdez, Beatriz; Abia, Rocío; Muriana, Francisco J G

2010-02-01

To briefly summarize recent advances towards understanding the influence of major dietary fatty acids on beta-cell function and evaluate their implications for insulin resistance. Studies in humans have shown that beta-cell function and insulin sensitivity improve progressively in the postprandial period as the proportion of monounsaturated fatty acids (MUFAs) with respect to saturated fatty acids (SFAs) in dietary fats increases. However, cell-culture experiments have revealed a dichotomy in the ability of fatty acids to moderate hyperactivity of, and induce lipotoxicity in, beta-cells. There are also some novel findings regarding the ability of HDL to protect beta-cells against oxidized LDL-induced apoptosis in vitro and of reconstituted HDL to attenuate insulin resistance in vivo. These findings raise new questions regarding the contribution of dietary fatty acids to insulin secretion and action. These new findings point to a critical role for major dietary fatty acids in the etiology and pathogenesis of diabetes, which appears to be of particular relevance during postprandial periods and mainly depends on the fatty acid type. This underscores the importance of dietary fatty acids in standard diabetes management.

HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity.

PubMed

Trusolino, L; Cavassa, S; Angelini, P; Andó, M; Bertotti, A; Comoglio, P M; Boccaccio, C

2000-08-01

Hepatocyte growth factor/scatter factor (HGF/SF) controls a genetic program known as 'invasive growth', which involves as critical steps cell adhesion, migration, and trespassing of basement membranes. We show here that in MDA-MB-231 carcinoma cells, these steps are elicited by HGF/SF but not by epidermal growth factor (EGF). Neither factor substantially alters the production or activity of extracellular matrix proteases. HGF/SF, but not EGF, selectively promotes cell adhesion on laminins 1 and 5, fibronectin, and vitronectin through a PI3-K-dependent mechanism. Increased adhesion is followed by enhanced invasiveness through isolated matrix proteins as well as through reconstituted basement membranes. Inhibition assays using function-blocking antibodies show that this phenomenon is mediated by multiple integrins including beta1, beta3, beta4, and beta5. HGF/SF triggers clustering of all these integrins at actin-rich adhesive sites and lamellipodia but does not quantitatively modify their membrane expression. These data suggest that HGF/SF promotes cell adhesion and invasiveness by increasing the avidity of integrins for their specific ligands.

Abnormalities of peptide metabolism in Alzheimer disease.

PubMed

Panchal, Maï; Rholam, Mohamed; Brakch, Noureddine

2004-10-01

The steady-state level of peptide hormones represents a balance between their biosynthesis and proteolytic processing by convertases and their catabolism by proteolytic enzymes. Low levels of neuropeptide Y, somatostatin and corticotropin-releasing factor, described in Alzheimer disease (AD), were related to a defect in proteolytic processing of their protein precursors. In contrast the abundance of beta-amyloid peptides, the major protein constituents of senile plaques is likely related to inefficient catabolism. Therefore, attention is mainly focused on convertases that generate active peptides and counter-regulatory proteases that are involved in their catabolism. Some well-described proteases such as NEP are thought to be involved in beta-amyloid catabolism. The search of other possible candidates represents a primary effort in the field. A variety of vascular risk factors such as diabetes, hypertension and arteriosclerosis suggest that the functional vascular defect contributes to AD pathology. It has also been described that beta-amyloid peptides potentiate endothelin-1 induced vasoconstriction. In this review, we will critically evaluate evidence relating proteases implicated in amyloid protein precursor proteolytic processing and beta-amyloid catabolism.

Conductivity fluctuations in polymer's networks

NASA Astrophysics Data System (ADS)

Samukhin, A. N.; Prigodin, V. N.; Jastrabík, L.

1998-01-01

A Polymer network is treated as an anisotropic fractal with fractional dimensionality D = 1 + ε close to one. Percolation model on such a fractal is studied. Using real space renormalization group approach of Migdal and Kadanoff, we find the threshold value and all the critical exponents in the percolation model to be strongly nonanalytic functions of ε, e.g. the critical exponent of the conductivity was obtained to be ε-2 exp (-1 - 1/ε). The main part of the finite-size conductivities distribution function at the threshold was found to be universal if expressed in terms of the fluctuating variable which is proportional to a large power of the conductivity, but with ε-dependent low-conductivity cut-off. Its reduced central momenta are of the order of e -1/ε up to a very high order.

Rumor Spreading Model with Trust Mechanism in Complex Social Networks

NASA Astrophysics Data System (ADS)

Wang, Ya-Qi; Yang, Xiao-Yuan; Han, Yi-Liang; Wang, Xu-An

2013-04-01

In this paper, to study rumor spreading, we propose a novel susceptible-infected-removed (SIR) model by introducing the trust mechanism. We derive mean-field equations that describe the dynamics of the SIR model on homogeneous networks and inhomogeneous networks. Then a steady-state analysis is conducted to investigate the critical threshold and the final size of the rumor spreading. We show that the introduction of trust mechanism reduces the final rumor size and the velocity of rumor spreading, but increases the critical thresholds on both networks. Moreover, the trust mechanism not only greatly reduces the maximum rumor influence, but also postpones the rumor terminal time, which provides us with more time to take measures to control the rumor spreading. The theoretical results are confirmed by sufficient numerical simulations.

Blister formation at subcritical doses in tungsten irradiated by MeV protons

NASA Astrophysics Data System (ADS)

Gavish Segev, I.; Yahel, E.; Silverman, I.; Makov, G.

2017-12-01

The material response of tungsten to irradiation by MeV protons has been studied experimentally, in particular with respect to bubble and blister formation. Tungsten samples were irradiated by 2.2 MeV protons at the Soreq Applied Research Accelerator Facility (SARAF) to doses of the order of 1017 protons/cm2 which are below the reported critical threshold for blister formation derived from keV range irradiation studies. Large, well-developed blisters are observed indicating that for MeV range protons the critical threshold is at least an order of magnitude lower than the lowest value reported previously. The effects of fluence, flux, and corresponding temperature on the distribution and characteristics of the obtained blisters were studied. FIB cross sections of several blisters exposed their depth and structure.

Disruption of the microbiota across multiple body sites in critically ill children.

PubMed

Rogers, Matthew B; Firek, Brian; Shi, Min; Yeh, Andrew; Brower-Sinning, Rachel; Aveson, Victoria; Kohl, Brittany L; Fabio, Anthony; Carcillo, Joseph A; Morowitz, Michael J

2016-12-29

Despite intense interest in the links between the microbiome and human health, little has been written about dysbiosis among ICU patients. We characterized microbial diversity in samples from 37 children in a pediatric ICU (PICU). Standard measures of alpha and beta diversity were calculated, and results were compared with data from adult and pediatric reference datasets. Bacterial 16S rRNA gene sequences were analyzed from 71 total tongue swabs, 50 skin swabs, and 77 stool samples or rectal swabs. The mean age of the PICU patients was 2.9 years (range 1-9 years), and many were chronically ill children that had previously been hospitalized in the PICU. Relative to healthy adults and children, alpha diversity was decreased in PICU GI and tongue but not skin samples. Measures of beta diversity indicated differences in community membership at each body site between PICU, adult, and pediatric groups. Taxonomic alterations in the PICU included enrichment of gut pathogens such as Enterococcus and Staphylococcus at multiple body sites and depletion of commensals such as Faecalibacterium and Ruminococcus from GI samples. Alpha and beta diversity were unstable over time in patients followed longitudinally. We observed the frequent presence of "dominant" pathogens in PICU samples at relative abundance >50%. PICU samples were characterized by loss of site specificity, with individual taxa commonly present simultaneously at three sample sites on a single individual. Some pathogens identified by culture of tracheal aspirates were commonly observed in skin samples from the same patient. We conclude that the microbiota in critically ill children differs sharply from the microbiota of healthy children and adults. Acknowledgement of dysbiosis associated with critical illness could provide opportunities to modulate the microbiota with precision and thereby improve patient outcomes.

Assessment of bone repair in critical-size defect in the calvarium of rats after the implantation of tricalcium phosphate beta (β-TCP).

PubMed

de Freitas Silva, Leonardo; de Carvalho Reis, Erik Neiva Ribeiro; Barbara, Tânia Aparecida; Bonardi, João Paulo; Garcia, Idelmo Rangel; de Carvalho, Paulo Sérgio Perri; Ponzoni, Daniela

2017-07-01

Evaluating the osteoconductive property of tricalcium phosphate beta (β-TCP) in comparison to that of inorganic bovine bone for repair in a critical-size defect in the rat calvarium. Critical-size defects of 7mm were made with a trephine in the calvaria of 48 Wistar rats. The animals were divided into four groups, and the defects in each group were filled with tricalcium phosphate beta (β-TCP), inorganic bovine bone (Bio-Oss), autogenous bone, or left empty. The animals were euthanized at two different time points (30 and 60days post-operation). All defects were recovered with a absorbable membrane of bovine cortical bone. Histological, histometric, and immunohistochemical (osteocalcin) assessments were carried out at 30 and 60days post-operation. At 30days post-operation, all groups showed areas of bone formation, predominantly when autogenous grafts were used. However, there were no statistically significant differences between the treatment groups (p>0.05). After 60days, there were similarities in the bone formation patterns between the β-TCP (26.32±) and Bio-Oss (17.35±) groups (p=0.549). In terms of the immunohistochemical assessment of osteocalcin, the clot group showed light to moderate staining at 30 and 60days. The autogenous group showed moderate staining at 30days and moderate to intense staining after 60days. The Bio-Oss group showed light to moderate staining after 30days and intense staining at 60days. The β-TCP group showed moderate staining at 30 and 60days post-operation. β-TCP is a good osteoconductive material with similar effects to those of inorganic bovine bone graft and is suitable for utilization in the repair of bone defects. Copyright © 2017 Elsevier GmbH. All rights reserved.

Hydrodynamic shear shows distinct roles for LFA-1 and Mac-1 in neutrophil adhesion to intercellular adhesion molecule-1.

PubMed

Neelamegham, S; Taylor, A D; Burns, A R; Smith, C W; Simon, S I

1998-09-01

The binding of neutrophil beta2 integrin to intercellular adhesion molecule-1 (ICAM-1) expressed on the inflamed endothelium is critical for neutrophil arrest at sites of tissue inflammation. To quantify the strength and kinetics of this interaction, we measured the adhesion between chemotactically stimulated neutrophils and ICAM-1-transfected mouse cells (E3-ICAM) in suspension in a cone-plate viscometer at shear rates typical of venular blood flow (100 s-1 to 500 s-1). The kinetics of aggregation were fit with a mathematical model based on two-body collision theory. This enabled estimation of adhesion efficiency, defined as the probability with which collisions between cells resulted in firm adhesion. The efficiency of beta2-integrin-dependent adhesion was highest ( approximately 0.2) at 100 s-1 and it decreased to approximately zero at 400 s-1. Both LFA-1 and Mac-1 contributed equally to adhesion efficiency over the initial 30 seconds of stimulation, but adhesion was entirely Mac-1-dependent by 120 seconds. Two hydrodynamic parameters were observed to influence integrin-dependent adhesion efficiency: the level of shear stress and the intercellular contact duration. Below a critical shear stress (<2 dyn/cm2), contact duration predominantly limited adhesion efficiency. The estimated minimum contact duration for beta2-integrin binding was approximately 6.5 ms. Above the critical shear stress (>2 dyn/cm2), the efficiency of neutrophil adhesion to E3-ICAM was limited by both the contact duration and the tensile stress. We conclude that at low shear, neutrophil adhesion is modulated independently through either LFA-1 or Mac-1, which initially contribute with equal efficiency, but differ over the duration of chemotactic stimulation. Copyright 1998 by The American Society of Hematology.

Dipole strength distributions from HIGS Experiments

NASA Astrophysics Data System (ADS)

Werner, V.; Cooper, N.; Goddard, P. M.; Humby, P.; Ilieva, R. S.; Rusev, G.; Beller, J.; Bernards, C.; Crider, B. P.; Isaak, J.; Kelley, J. H.; Kwan, E.; Löher, B.; Peters, E. E.; Pietralla, N.; Romig, C.; Savran, D.; Scheck, M.; Tonchev, A. P.; Tornow, W.; Yates, S. W.; Zweidinger, M.

2015-05-01

A series of photon scattering experiments has been performed on the double-beta decay partners 76Ge and 76Se, in order to investigate their dipole response up to the neutron separation threshold. Gamma-ray beams from bremsstrahlung at the S-DALINAC and from Compton-backscattering at HIGS have been used to measure absolute cross sections and parities of dipole excited states, respectively. The HIGS data allows for indirect measurement of averaged branching ratios, which leads to significant corrections in the observed excitation cross sections. Results are compared to statistical calculations, to test photon strength functions and the Axel-Brink hypothesis

Dark matter search with CUORE-0 and CUORE

DOE PAGES

Aguirre, C. P.; Artusa, D. R.; Avignone, F. T.; ...

2015-01-01

The Cryogenic Underground Observatory for Rare Events (CUORE) is a ton-scale experiment made of TeO₂ bolometers that will probe the neutrinoless double beta decay of ¹³⁰Te. Excellent energy resolution, low threshold and low background make CUORE sensitive to nuclear recoils, allowing a search for dark matter interactions. With a total mass of 741 kg of TeO₂, CUORE can search for an annual modulation of the counting rate at low energies. We present data obtained with CUORE-like detectors and the prospects for a dark matter search in CUORE-0, a 40-kg prototype, and CUORE.

Usefulness of threshold dose to prevent damage of underlying tissue by PDT treatment: an in-vitro study on chondrocytes

NASA Astrophysics Data System (ADS)

Placzek, R.; Kempka, G.; Ruether, W.; Moser, Joerg G.

1995-03-01

Arthritic synovitis is best cured by total removal of the inflamed synovia (equals synovectomy). This can be performed by open chirurgy, by arthroscopy, or by radiosynoviothesis, i.e., injection of (beta) -radiating rare earth metals into the joint cavity. All these procedures are more or less non-quantitative and may lead to a recidive. The idea was to destroy the inflamed synovia by PDT without destruction of the underlying tissue (cartilage and bone). So, the sensitivity of the cartilage-building cells, which can be grown in cell culture, has to be studied.

The role of beta-endorphin in the pathophysiology of major depression.

PubMed

Hegadoren, K M; O'Donnell, T; Lanius, R; Coupland, N J; Lacaze-Masmonteil, N

2009-10-01

A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta-END in the pathophysiology of MDD must be paralleled by consensus building within the research community around the heterogeneity inherent in mood disorders, standardization of experimental protocols, improved discrimination of POMC products in analytical techniques and consistent attention paid to important confounds like age and gender.

Investigation of the effects of P2 purinoceptor ligands on the micturition reflex in female urethane-anaesthetized rats.

PubMed

King, Brian F; Knowles, Ian D; Burnstock, Geoffrey; Ramage, Andrew G

2004-06-01

1 The effects of purinoceptor ligands for P2X1 and/or P2X3 receptors (alpha,beta-meATP, IP(5)I, TNP-ATP, MRS 2179, PPADS, Phenol red and RO116-6446/008; i.v., n=4-5) and for P2Y1 receptors (PPADS, MRS 2179 and MRS 2269; i.v., n=3-5) were investigated on the distension-evoked 'micturition reflex' in the urethane-anaesthetized female rat. 2 Alpha,beta-meATP (180 nmol kg(-1) min(-1)), IP5I (10, 30 and 100 nmol kg(-1)), TNP-ATP (1 micromol kg(-1)), MRS 2179 (1 micromol kg(-1)) and PPADS (17 micromol kg(-1)) each caused maintained bladder contractions to occur during the infusion of saline into the bladder. PPADS (17 micromol kg(-1) min(-1)) had a similar effect when infused intravesicularly. Regular bladder contractions were not observed until the infusion of saline was halted. For IP5I, TNP-ATP, MRS 2179 and PPADS, the magnitude of postinfusion isovolumetric contractions was significantly reduced and, for IP5I, this action was also associated with a significant reduction in urethral relaxation. Additionally, TNP-ATP caused a significant increase in the pressure and volume thresholds required to initiate a reflex. 3 Phenol red (a P2X1/P2X3 antagonist; 0.1 and 1 micromol kg(-1)) caused a significant increase in the pressure and volume thresholds required to initiate a reflex and, at the higher dose, also caused a reduction in postinfusion isovolumetric contractions. 4 RO116-6446/008 (a P2X1-selective antagonist; 1 and 10 micromol kg(-1)) only caused a reduction in postinfusion isovolumetric contractions. 5 It is concluded that P2X1 and P2X3 receptors play a fundamental role in the micturition reflex in urethane-anesthetized female rats. P2X3 receptor blockade raised the pressure and volume thresholds for the reflex, whereas P2X1 receptor blockade diminished motor activity associated with voiding. P2Y1 receptors may be involved in inhibition of rat detrusor tone.

Development of the new trigger for VANDLE neutron detector

NASA Astrophysics Data System (ADS)

Hasse, Adam; Taylor, Steven; Daugherty, Hadyn; Grzywacz, Robert

2014-09-01

Beta-delayed neutron emission (βn) is the dominant decay channel for the majority of very neutron-rich nuclei. In order to study these decays a new detector system called the Versatile Array of Neutron Detectors at Low Energy (VANDLE) was constructed. A critical part of this neutron time of flight detector is a trigger unit. This trigger is sensitive to electron from beta decay down to very low energies, insensitive to gamma rays and have a good timing performance, better than 1 ns. In order to satisfy these condition, we have developed a new system, which utilizes plastic scintillator but uses recently developed light readout technique, based on the so called Silicon Photomultiplier, manufactured by Sensl. New system has been developed and performance tested using digital data acquisition system at the University of Tennessee and will be utilized in future experiments involving VANDLE. Beta-delayed neutron emission (βn) is the dominant decay channel for the majority of very neutron-rich nuclei. In order to study these decays a new detector system called the Versatile Array of Neutron Detectors at Low Energy (VANDLE) was constructed. A critical part of this neutron time of flight detector is a trigger unit. This trigger is sensitive to electron from beta decay down to very low energies, insensitive to gamma rays and have a good timing performance, better than 1 ns. In order to satisfy these condition, we have developed a new system, which utilizes plastic scintillator but uses recently developed light readout technique, based on the so called Silicon Photomultiplier, manufactured by Sensl. New system has been developed and performance tested using digital data acquisition system at the University of Tennessee and will be utilized in future experiments involving VANDLE. Department of Physics and Astronomy, University of Tennessee, Knoxville, USA.

The use of spatio-temporal correlation to forecast critical transitions

NASA Astrophysics Data System (ADS)

Karssenberg, Derek; Bierkens, Marc F. P.

2010-05-01

Complex dynamical systems may have critical thresholds at which the system shifts abruptly from one state to another. Such critical transitions have been observed in systems ranging from the human body system to financial markets and the Earth system. Forecasting the timing of critical transitions before they are reached is of paramount importance because critical transitions are associated with a large shift in dynamical regime of the system under consideration. However, it is hard to forecast critical transitions, because the state of the system shows relatively little change before the threshold is reached. Recently, it was shown that increased spatio-temporal autocorrelation and variance can serve as alternative early warning signal for critical transitions. However, thus far these second order statistics have not been used for forecasting in a data assimilation framework. Here we show that the use of spatio-temporal autocorrelation and variance in the state of the system reduces the uncertainty in the predicted timing of critical transitions compared to classical approaches that use the value of the system state only. This is shown by assimilating observed spatio-temporal autocorrelation and variance into a dynamical system model using a Particle Filter. We adapt a well-studied distributed model of a logistically growing resource with a fixed grazing rate. The model describes the transition from an underexploited system with high resource biomass to overexploitation as grazing pressure crosses the critical threshold, which is a fold bifurcation. To represent limited prior information, we use a large variance in the prior probability distributions of model parameters and the system driver (grazing rate). First, we show that the rate of increase in spatio-temporal autocorrelation and variance prior to reaching the critical threshold is relatively consistent across the uncertainty range of the driver and parameter values used. This indicates that an increase in spatio-temporal autocorrelation and variance are consistent predictors of a critical transition, even under the condition of a poorly defined system. Second, we perform data assimilation experiments using an artificial exhaustive data set generated by one realization of the model. To mimic real-world sampling, an observational data set is created from this exhaustive data set. This is done by sampling on a regular spatio-temporal grid, supplemented by sampling locations at a short distance. Spatial and temporal autocorrelation in this observational data set is calculated for different spatial and temporal separation (lag) distances. To assign appropriate weights to observations (here, autocorrelation values and variance) in the Particle Filter, the covariance matrix of the error in these observations is required. This covariance matrix is estimated using Monte Carlo sampling, selecting a different random position of the sampling network relative to the exhaustive data set for each realization. At each update moment in the Particle Filter, observed autocorrelation values are assimilated into the model and the state of the model is updated. Using this approach, it is shown that the use of autocorrelation reduces the uncertainty in the forecasted timing of a critical transition compared to runs without data assimilation. The performance of the use of spatial autocorrelation versus temporal autocorrelation depends on the timing and number of observational data. This study is restricted to a single model only. However, it is becoming increasingly clear that spatio-temporal autocorrelation and variance can be used as early warning signals for a large number of systems. Thus, it is expected that spatio-temporal autocorrelation and variance are valuable in data assimilation frameworks in a large number of dynamical systems.

Rising intracellular zinc by membrane depolarization and glucose in insulin-secreting clonal HIT-T15 beta cells.

PubMed

Slepchenko, Kira G; Li, Yang V

2012-01-01

Zinc (Zn(2+)) appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30-60 mM) was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM) induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

Fast ion beta limit measurements by collimated neutron detection in MST plasmas

NASA Astrophysics Data System (ADS)

Capecchi, William; Anderson, Jay; Bonofiglo, Phillip; Kim, Jungha; Sears, Stephanie

2015-11-01

Fast ion orbits in the reversed field pinch (RFP) are well ordered and classically confined despite magnetic field stochasticity generated by multiple tearing modes. Classical TRANSP modeling of a 1MW tangentially injected hydrogen neutral beam in MST deuterium plasmas predicts a core-localized fast ion density that can be up to 25% of the electron density and a fast ion beta of many times the local thermal beta. However, neutral particle analysis of an NBI-driven mode (presumably driven by a fast ion pressure gradient) shows mode-induced transport of core-localized fast ions and a saturated fast ion density. The TRANSP modeling is presumed valid until the onset of the beam-driven mode and gives an initial estimate of the volume-averaged fast ion beta of 1-2% (local core value up to 10%). A collimated neutron detector for fusion product profile measurements will be used to determine the spatial distribution of fast ions, allowing for a first measurement of the critical fast-ion pressure gradient required for mode destabilization. Testing/calibration data and initial fast-ion profiles will be presented. Characterization of both the local and global fast ion beta will be done for deuterium beam injection into deuterium plasmas for comparison to TRANSP predictions. Work supported by US DOE.

Effects of rhythmic stimulus presentation on oscillatory brain activity: the physiology of cueing in Parkinson’s disease

PubMed Central

te Woerd, Erik S.; Oostenveld, Robert; Bloem, Bastiaan R.; de Lange, Floris P.; Praamstra, Peter

2015-01-01

The basal ganglia play an important role in beat perception and patients with Parkinson’s disease (PD) are impaired in perception of beat-based rhythms. Rhythmic cues are nonetheless beneficial in gait rehabilitation, raising the question how rhythm improves movement in PD. We addressed this question with magnetoencephalography recordings during a choice response task with rhythmic and non-rhythmic modes of stimulus presentation. Analyses focused on (i) entrainment of slow oscillations, (ii) the depth of beta power modulation, and (iii) whether a gain in modulation depth of beta power, due to rhythmicity, is of predictive or reactive nature. The results show weaker phase synchronisation of slow oscillations and a relative shift from predictive to reactive movement-related beta suppression in PD. Nonetheless, rhythmic stimulus presentation increased beta modulation depth to the same extent in patients and controls. Critically, this gain selectively increased the predictive and not reactive movement-related beta power suppression. Operation of a predictive mechanism, induced by rhythmic stimulation, was corroborated by a sensory gating effect in the sensorimotor cortex. The predictive mode of cue utilisation points to facilitation of basal ganglia-premotor interactions, contrasting with the popular view that rhythmic stimulation confers a special advantage in PD, based on recruitment of alternative pathways. PMID:26509117

Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.

PubMed

Schank, Jesse R; Liles, L Cameron; Weinshenker, David

2008-06-01

Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.

Effects of beta-alanine supplementation and high-intensity interval training on endurance performance and body composition in men; a double-blind trial.

PubMed

Smith, Abbie E; Walter, Ashley A; Graef, Jennifer L; Kendall, Kristina L; Moon, Jordan R; Lockwood, Christopher M; Fukuda, David H; Beck, Travis W; Cramer, Joel T; Stout, Jeffrey R

2009-02-11

Intermittent bouts of high-intensity exercise result in diminished stores of energy substrates, followed by an accumulation of metabolites, promoting chronic physiological adaptations. In addition, beta-alanine has been accepted has an effective physiological hydrogen ion (H+) buffer. Concurrent high-intensity interval training (HIIT) and beta-alanine supplementation may result in greater adaptations than HIIT alone. The purpose of the current study was to evaluate the effects of combining beta-alanine supplementation with high-intensity interval training (HIIT) on endurance performance and aerobic metabolism in recreationally active college-aged men. Forty-six men (Age: 22.2 +/- 2.7 yrs; Ht: 178.1 +/- 7.4 cm; Wt: 78.7 +/- 11.9; VO2peak: 3.3 +/- 0.59 l.min-1) were assessed for peak O2 utilization (VO2peak), time to fatigue (VO2TTE), ventilatory threshold (VT), and total work done at 110% of pre-training VO2peak (TWD). In a double-blind fashion, all subjects were randomly assigned into one either a placebo (PL - 16.5 g dextrose powder per packet; n = 18) or beta-alanine (BA - 1.5 g beta-alanine plus 15 g dextrose powder per packet; n = 18) group. All subjects supplemented four times per day (total of 6 g/day) for the first 21-days, followed by two times per day (3 g/day) for the subsequent 21 days, and engaged in a total of six weeks of HIIT training consisting of 5-6 bouts of a 2:1 minute cycling work to rest ratio. Significant improvements in VO2peak, VO2TTE, and TWD after three weeks of training were displayed (p < 0.05). Increases in VO2peak, VO2TTE, TWD and lean body mass were only significant for the BA group after the second three weeks of training. The use of HIIT to induce significant aerobic improvements is effective and efficient. Chronic BA supplementation may further enhance HIIT, improving endurance performance and lean body mass.

Assessing human health response in life cycle assessment using ED10s and DALYs: part 2--Noncancer effects.

PubMed

Pennington, David; Crettaz, Pierre; Tauxe, Annick; Rhomberg, Lorenz; Brand, Kevin; Jolliet, Olivier

2002-10-01

In Part 1 of this article we developed an approach for the calculation of cancer effect measures for life cycle assessment (LCA). In this article, we propose and evaluate the method for the screening of noncancer toxicological health effects. This approach draws on the noncancer health risk assessment concept of benchmark dose, while noting important differences with regulatory applications in the objectives of an LCA study. We adopt the centraltendency estimate of the toxicological effect dose inducing a 10% response over background, ED10, to provide a consistent point of departure for default linear low-dose response estimates (betaED10). This explicit estimation of low-dose risks, while necessary in LCA, is in marked contrast to many traditional procedures for noncancer assessments. For pragmatic reasons, mechanistic thresholds and nonlinear low-dose response curves were not implemented in the presented framework. In essence, for the comparative needs of LCA, we propose that one initially screens alternative activities or products on the degree to which the associated chemical emissions erode their margins of exposure, which may or may not be manifested as increases in disease incidence. We illustrate the method here by deriving the betaED10 slope factors from bioassay data for 12 chemicals and outline some of the possibilities for extrapolation from other more readily available measures, such as the no observable adverse effect levels (NOAEL), avoiding uncertainty factors that lead to inconsistent degrees of conservatism from chemical to chemical. These extrapolations facilitated the initial calculation of slope factors for an additional 403 compounds; ranging from 10(-6) to 10(3) (risk per mg/kg-day dose). The potential consequences of the effects are taken into account in a preliminary approach by combining the betaED10 with the severity measure disability adjusted life years (DALY), providing a screening-level estimate of the potential consequences associated with exposures, integrated over time and space, to a given mass of chemical released into the environment for use in LCA.

The Threshold Shortest Path Interdiction Problem for Critical Infrastructure Resilience Analysis

DTIC Science & Technology

2017-09-01

being pushed over the minimum designated threshold. 1.4 Motivation A simple setting to motivate this research is the “30 minutes or it’s free” guarantee...parallel network structure in Fig. 4.4 is simple in design , yet shows a relatively high resilience when compared to the other networks in general. The high...United States Naval Academy, 2002 Submitted in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE IN OPERATIONS RESEARCH

Threshold Phenomenon for the Quintic Wave Equation in Three Dimensions

NASA Astrophysics Data System (ADS)

Krieger, Joachim; Nakanishi, Kenji; Schlag, Wilhelm

2014-04-01

For the critical focusing wave equation in the radial case, we establish the role of the "center stable" manifold constructed in Krieger and Schlag (Am J Math 129(3):843-913, 2007) near the ground state ( W, 0) as a threshold between blowup and scattering to zero, establishing a conjecture going back to numerical work by Bizoń et al. (Nonlinearity 17(6):2187-2201, 2004). The underlying topology is stronger than the energy norm.

Synchronization on Erdös-Rényi networks.

PubMed

Gong, Baihua; Yang, Lei; Yang, Kongqing

2005-09-01

In this Brief Report, by analyzing the spectral properties of the Laplacian matrix of Erdös-Rényi networks, we obtained the critical coupling strength of the complete synchronization analytically. In particular, for any size of the networks, when the average degree is greater than a threshold and the coupling strength is large enough, the networks can synchronize. Here, the threshold is determined by the value of the maximal Lyapunov exponent of each dynamical unit.

Sun glint requirement for the remote detection of surface oil films

NASA Astrophysics Data System (ADS)

Sun, Shaojie; Hu, Chuanmin

2016-01-01

Natural oil slicks in the western Gulf of Mexico are used to determine the sun glint threshold required for optical remote sensing of oil films. The threshold is determined using the same-day image pairs collected by Moderate Resolution Imaging Spectroradiometer (MODIS) Terra (MODIST), MODIS Aqua (MODISA), and Visible Infrared Imaging Radiometer Suite (VIIRS) (N = 2297 images) over the same oil slick locations where at least one of the sensors captures the oil slicks. For each sensor, statistics of sun glint strengths, represented by the normalized glint reflectance (LGN, sr-1), when oil slicks can and cannot be observed are generated. The LGN threshold for oil film detections is determined to be 10-5-10-6 sr-1 for MODIST and MODISA, and 10-6-10-7 sr-1 for VIIRS. Below these thresholds, no oil films can be detected, while above these thresholds, oil films can always be detected except near the critical-angle zone where oil slicks reverse their contrast against the background water.

Ineffectiveness of intravenous beta 2-agonists on improving exercise tolerance in patients with reversible chronic airway obstruction.

PubMed

Malerba, M; Boni, E; Tantucci, C; Filippi, B; Romagnoni, G; Grassi, V

1996-01-01

The effects on exercise tolerance after acute administration of beta 2-agonists were investigated in 11 patients with partly reversible chronic airway obstruction after 400 micrograms of salbutamol (S) given intravenously (i.v.) and after 400 micrograms i.v. of a new selective beta 2-agonist, broxaterol (B), by a cardiopulmonary incremental exercise test. At rest, while VE increased in respect to basal conditions (C) after S (from 13.3 +/- 2.2 to 14.4 +/- 2.8 l/min; p < 0.05) and after B (from 13.6 +/- 3.1 to 15.5 +/- 3.6 l/min; p < 0.05), VO2, VCO2 and VO2/HR showed no substantial variations. A small, not significant reduction of PaO2 was observed both after S (from 82.7 +/- 11.7 to 79.1 +/- 16.7 mm Hg) and B (from 81.6 +/- 10.5 to 78.0 +/- 11.0 mm Hg). The maximum workload increased neither after S (from 67.5 +/- 39.1 to 66.6 +/- 37.0 W) nor after B (from 65.7 +/- 39.3 to 60.0 +/- 35.8 W). At peak of exercise, VO2, VCO2 and VO2/HR did not change after S and B as compared with C, whereas VE remained higher after both beta 2-agonists throughout the effort. VO2 at ventilatory anaerobic threshold (AT) was significantly greater either after S (from 744 +/- 378 to 815 +/- 302 ml/min; p < 0.05) and after B (from 756 +/- 290 to 842 +/- 292 ml/min; p < 0.05). The PaO2 increase shown by these patients during effort was greater after beta 2-agonists administration, delta PaO2 from rest to peak of exercise amounting to 14.9 +/- 14.3 vs. 7.8 +/- 8.2 mm Hg after S and to 17.8 +/- 15.1 vs. 8.8 +/- 10.9 mm Hg after B, in respect to relative baseline (p < 0.05). We conclude that beta 2-agonists, when given acutely, do not improve exercise tolerance in patients with reversible chronic airflow obstruction, although these drugs can induce a small increment of ventilatory AT. In addition, arterial blood gases do not deteriorate at rest and are better preserved during exercise after beta 2-agonists.

Short communication: use of the BetaStar Plus assay for detection of ceftiofur antimicrobial residues in milk from individual cows following intramammary treatment for mastitis.

PubMed

Grooms, D L; Norby, B; Grooms, K E; Jagodzinski, E N; Erskine, R J; Halbert, L W; Coetzee, J F; Wulf, L; Rice, J A

2015-09-01

Development and use of on-farm assays to detect antimicrobial residues in milk is important to reduce the risk of violative residues in marketed milk. The objective of this study was to evaluate the effectiveness of a lateral-flow immunodiagnostic assay (BetaStar Plus, Neogen Corp., Lansing, MI) in detecting ceftiofur residues in milk from individual cows treated for mastitis. This assay is currently approved by the US Federal Drug Administration (FDA) for detecting β-lactam residues in commingled milk. Forty-five dairy cows with clinical mastitis from 4 dairy farms were enrolled and treated intramammary with 125 mg of ceftiofur hydrochloride (Spectramast LC, Zoetis, Madison, NJ) according to the manufacturer's label recommendation. Composite milk samples were collected (A) before first intramammary antimicrobial treatment, (B) before the last intramammary antimicrobial treatment, (C) the last milking of the product-labeled milk withhold, (D) the first milking after the product-labeled milk withhold had been met, and (E) 72 h after the product-labeled milk withhold had been met. Samples were tested using the BetaStar Plus assay within 48 h of collection. Parallel samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and for somatic cell count and milk components. The BetaStar Plus assay identified 6.7, 60.0, 46.7, 22.2, and 6.7% positive samples at each of the respective time points. The assay had sensitivity and specificity of 100 and 84.7%, respectively, compared with liquid chromatography-tandem mass spectrometry analysis using FDA published residue tolerance levels for ceftiofur (or ceftiofur metabolites) as a threshold. The BetaStar Plus assay could be useful for detecting ceftiofur residues in milk from individual cows following intramammary treatment for mastitis before the milk is shipped for processing. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of chronic NaHCO3 ingestion during interval training on changes to muscle buffer capacity, metabolism, and short-term endurance performance.

PubMed

Edge, Johann; Bishop, David; Goodman, Carmel

2006-09-01

This study determined the effects of altering the H(+) concentration during interval training, by ingesting NaHCO(3) (Alk-T) or a placebo (Pla-T), on changes in muscle buffer capacity (beta m), endurance performance, and muscle metabolites. Pre- and posttraining peak O(2) uptake (V(O2 peak)), lactate threshold (LT), and time to fatigue at 100% pretraining V(O2 peak) intensity were assessed in 16 recreationally active women. Subjects were matched on the LT, were randomly placed into the Alk-T (n = 8) or Pla-T (n = 8) groups, and performed 8 wk (3 days/wk) of six to twelve 2-min cycle intervals at 140-170% of their LT, ingesting NaHCO(3) or a placebo before each training session (work matched between groups). Both groups had improvements in beta m (19 vs. 9%; P < 0.05) and V(O2 peak) (22 vs. 17%; P < 0.05) after the training period, with no differences between groups. There was a significant correlation between pretraining beta m and percent change in beta m (r = -0.70, P < 0.05). There were greater improvements in both the LT (26 vs. 15%; P = 0.05) and time to fatigue (164 vs. 123%; P = 0.05) after Alk-T, compared with Pla-T. There were no changes to pre- or postexercise ATP, phosphocreatine, creatine, and intracellular lactate concentrations, or pH(i) after training. Our findings suggest that training intensity, rather than the accumulation of H(+) during training, may be more important to improvements in beta m. The group ingesting NaHCO(3) before each training session had larger improvements in the LT and endurance performance, possibly because of a reduced metabolic acidosis during training and a greater improvement in muscle oxidative capacity.

Using Critical Race Theory to Analyze How Disney Constructs Diversity: A Construct for the Baccalaureate Human Behavior in the Social Environment Curriculum

ERIC Educational Resources Information Center

Cappiccie, Amy; Chadha, Janice; Lin, Muh Bi; Snyder, Frank

2012-01-01

Utilizing the basic tenets of critical race theory, the authors draw upon the expertise of multicultural scholars to raise consciousness and facilitate BSW classroom dialogue about microagressions perpetrated in Disney animations. Microaggressions pervade our media partly because they typically operate outside the threshold of the dominant…

Predicting the Lifetime of Dynamic Networks Experiencing Persistent Random Attacks.

PubMed

Podobnik, Boris; Lipic, Tomislav; Horvatic, Davor; Majdandzic, Antonio; Bishop, Steven R; Eugene Stanley, H

2015-09-21

Estimating the critical points at which complex systems abruptly flip from one state to another is one of the remaining challenges in network science. Due to lack of knowledge about the underlying stochastic processes controlling critical transitions, it is widely considered difficult to determine the location of critical points for real-world networks, and it is even more difficult to predict the time at which these potentially catastrophic failures occur. We analyse a class of decaying dynamic networks experiencing persistent failures in which the magnitude of the overall failure is quantified by the probability that a potentially permanent internal failure will occur. When the fraction of active neighbours is reduced to a critical threshold, cascading failures can trigger a total network failure. For this class of network we find that the time to network failure, which is equivalent to network lifetime, is inversely dependent upon the magnitude of the failure and logarithmically dependent on the threshold. We analyse how permanent failures affect network robustness using network lifetime as a measure. These findings provide new methodological insight into system dynamics and, in particular, of the dynamic processes of networks. We illustrate the network model by selected examples from biology, and social science.

Mechanism of Resilin Elasticity

PubMed Central

Qin, Guokui; Hu, Xiao; Cebe, Peggy; Kaplan, David L.

2012-01-01

Resilin is critical in the flight and jumping systems of insects as a polymeric rubber-like protein with outstanding elasticity. However, insight into the underlying molecular mechanisms responsible for resilin elasticity remains undefined. Here we report the structure and function of resilin from Drosophila CG15920. A reversible beta-turn transition was identified in the peptide encoded by exon III and for full length resilin during energy input and release, features that correlate to the rapid deformation of resilin during functions in vivo. Micellar structures and nano-porous patterns formed after beta-turn structures were present via changes in either the thermal or mechanical inputs. A model is proposed to explain the super elasticity and energy conversion mechanisms of resilin, providing important insight into structure-function relationships for this protein. Further, this model offers a view of elastomeric proteins in general where beta-turn related structures serve as fundamental units of the structure and elasticity. PMID:22893127

Laser-induced propagation and destruction of amyloid beta fibrils.

PubMed

Yagi, Hisashi; Ozawa, Daisaku; Sakurai, Kazumasa; Kawakami, Toru; Kuyama, Hiroki; Nishimura, Osamu; Shimanouchi, Toshinori; Kuboi, Ryoichi; Naiki, Hironobu; Goto, Yuji

2010-06-18

The amyloid deposition of amyloid beta (Abeta) peptides is a critical pathological event in Alzheimer disease (AD). Preventing the formation of amyloid deposits and removing preformed fibrils in tissues are important therapeutic strategies against AD. Previously, we reported the destruction of amyloid fibrils of beta(2)-microglobulin K3 fragments by laser irradiation coupled with the binding of amyloid-specific thioflavin T. Here, we studied the effects of a laser beam on Abeta fibrils. As was the case for K3 fibrils, extensive irradiation destroyed the preformed Abeta fibrils. However, irradiation during spontaneous fibril formation resulted in only the partial destruction of growing fibrils and a subsequent explosive propagation of fibrils. The explosive propagation was caused by an increase in the number of active ends due to breakage. The results not only reveal a case of fragmentation-induced propagation of fibrils but also provide insights into therapeutic strategies for AD.

Age-related pulmonary emphysema in mice lacking alpha/beta hydrolase domain containing 2 gene.

PubMed

Jin, Shoude; Zhao, Gang; Li, Zhenghua; Nishimoto, Yuki; Isohama, Yoichiro; Shen, Jingling; Ito, Takaaki; Takeya, Motohiro; Araki, Kimi; He, Ping; Yamamura, Ken-ichi

2009-03-06

The alpha/beta hydrolase family genes have been identified as down-regulated genes in human emphysematous lungs. Although proteins in the alpha/beta hydrolase family generally act as enzymes, such as lipases, the specific functions of the Abhd2 protein are unknown. To examine the role of Abhd2 in the lung, we analyzed Abhd2 deficient mice obtained by gene trap mutagenesis. Abhd2 was expressed in the alveolar type II cells. Abhd2 deficiency resulted in a decreased level of phosphatidylcholine in the bronchoalveolar lavage. These mice developed spontaneous gradual progression of emphysema, due to increased macrophage infiltration, increased inflammatory cytokines, a protease/anti-protease imbalance and enhanced apoptosis. This phenotype is more akin to the pace of emphysema that develops in humans. Our findings suggest that derangement in alveolar phospholipid metabolism can induce emphysema, and that Abhd2 plays a critical role in maintaining lung structural integrity.

Importin Beta Plays an Essential Role in the Regulation of the LysRS-Ap4A Pathway in Immunologically Activated Mast Cells ▿

PubMed Central

Carmi-Levy, Irit; Motzik, Alex; Ofir-Birin, Yifat; Yagil, Zohar; Yang, Christopher Maolin; Kemeny, David Michael; Han, Jung Min; Kim, Sunghoon; Kay, Gillian; Nechushtan, Hovav; Suzuki, Ryo; Rivera, Juan; Razin, Ehud

2011-01-01

We recently reported that diadenosine tetraphosphate hydrolase (Ap4A hydrolase) plays a critical role in gene expression via regulation of intracellular Ap4A levels. This enzyme serves as a component of our newly described lysyl tRNA synthetase (LysRS)-Ap4A biochemical pathway that is triggered upon immunological challenge. Here we explored the mechanism of this enzyme's translocation into the nucleus and found its immunologically dependent association with importin beta. Silencing of importin beta prevented Ap4A hydrolase nuclear translocation and affected the local concentration of Ap4A, which led to an increase in microphthalmia transcription factor (MITF) transcriptional activity. Furthermore, immunological activation of mast cells resulted in dephosphorylation of Ap4A hydrolase, which changed the hydrolytic activity of the enzyme. PMID:21402779

Foot-and-mouth disease virus leader proteinase inhibits dsRNA-induced type I interferon transcription by decreasing interferon regulatory factor 3/7 in protein levels

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

Wang, Dang; Fang, Liurong; Luo, Rui

2010-08-13

Research highlights: {yields} FMDV L{sup pro} inhibits poly(I:C)-induced IFN-{alpha}1/{beta} mRNA expression. {yields} L{sup pro} inhibits MDA5-mediated activation of the IFN-{alpha}1/{beta} promoter. {yields} L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes. {yields} L{sup pro} inhibits IFN-{alpha}1/{beta} promoter activation by decreasing IRF-3/7 in protein levels. {yields} The ability to process eIF-4G of L{sup pro} is not necessary to inhibit IFN-{alpha}1/{beta} activation. -- Abstract: The leader proteinase (L{sup pro}) of foot-and-mouth disease virus (FMDV) has been identified as an interferon-{beta} (IFN-{beta}) antagonist that disrupts the integrity of transcription factor nuclear factor {kappa}B (NF-{kappa}B). In this study, we showed that the reductionmore » of double stranded RNA (dsRNA)-induced IFN-{alpha}1/{beta} expression caused by L{sup pro} was also associated with a decrease of interferon regulatory factor 3/7 (IRF-3/7) in protein levels, two critical transcription factors for activation of IFN-{alpha}/{beta}. Furthermore, overexpression of L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes including 2',5'-OAS, ISG54, IP-10, and RANTES. Screening L{sup pro} mutants indicated that the ability to process eIF-4G of L{sup pro} is not required for suppressing dsRNA-induced activation of the IFN-{alpha}1/{beta} promoter and decreasing IRF-3/7 expression. Taken together, our results demonstrate that, in addition to disrupting NF-{kappa}B, L{sup pro} also decreases IRF-3/7 expression to suppress dsRNA-induced type I IFN production, suggesting multiple strategies used by FMDV to counteract the immune response to viral infection.« less

Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

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

Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.

2011-03-11

Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomicsmore » screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.« less

Objective definition of rainfall intensity-duration thresholds for the initiation of post-fire debris flows in southern California

USGS Publications Warehouse

Staley, Dennis; Kean, Jason W.; Cannon, Susan H.; Schmidt, Kevin M.; Laber, Jayme L.

2012-01-01

Rainfall intensity–duration (ID) thresholds are commonly used to predict the temporal occurrence of debris flows and shallow landslides. Typically, thresholds are subjectively defined as the upper limit of peak rainstorm intensities that do not produce debris flows and landslides, or as the lower limit of peak rainstorm intensities that initiate debris flows and landslides. In addition, peak rainstorm intensities are often used to define thresholds, as data regarding the precise timing of debris flows and associated rainfall intensities are usually not available, and rainfall characteristics are often estimated from distant gauging locations. Here, we attempt to improve the performance of existing threshold-based predictions of post-fire debris-flow occurrence by utilizing data on the precise timing of debris flows relative to rainfall intensity, and develop an objective method to define the threshold intensities. We objectively defined the thresholds by maximizing the number of correct predictions of debris flow occurrence while minimizing the rate of both Type I (false positive) and Type II (false negative) errors. We identified that (1) there were statistically significant differences between peak storm and triggering intensities, (2) the objectively defined threshold model presents a better balance between predictive success, false alarms and failed alarms than previous subjectively defined thresholds, (3) thresholds based on measurements of rainfall intensity over shorter duration (≤60 min) are better predictors of post-fire debris-flow initiation than longer duration thresholds, and (4) the objectively defined thresholds were exceeded prior to the recorded time of debris flow at frequencies similar to or better than subjective thresholds. Our findings highlight the need to better constrain the timing and processes of initiation of landslides and debris flows for future threshold studies. In addition, the methods used to define rainfall thresholds in this study represent a computationally simple means of deriving critical values for other studies of nonlinear phenomena characterized by thresholds.

Price of anarchy is maximized at the percolation threshold.

PubMed

Skinner, Brian

2015-05-01

When many independent users try to route traffic through a network, the flow can easily become suboptimal as a consequence of congestion of the most efficient paths. The degree of this suboptimality is quantified by the so-called price of anarchy (POA), but so far there are no general rules for when to expect a large POA in a random network. Here I address this question by introducing a simple model of flow through a network with randomly placed congestible and incongestible links. I show that the POA is maximized precisely when the fraction of congestible links matches the percolation threshold of the lattice. Both the POA and the total cost demonstrate critical scaling near the percolation threshold.

Ultralow-threshold microcavity Raman laser on a microelectronic chip

NASA Astrophysics Data System (ADS)

Kippenberg, T. J.; Spillane, S. M.; Armani, D. K.; Vahala, K. J.

2004-06-01

Using ultrahigh-Q toroid microcavities on a chip, we demonstrate a monolithic microcavity Raman laser. Cavity photon lifetimes in excess of 100 ns combined with mode volumes typically of less than 1000 µm^3 significantly reduce the threshold for stimulated Raman scattering. In conjunction with the high ideality of a tapered optical fiber coupling junction, stimulated Raman lasing is observed at an ultralow threshold (as low as 74 µW of fiber-launched power at 1550 nm) with high efficiency (up to 45% at the critical coupling point) in good agreement with theoretical modeling. Equally important, the wafer-scale nature of these devices should permit integration with other photonic, mechanical, or electrical functionality on a chip.

Ultralow-threshold microcavity Raman laser on a microelectronic chip.

PubMed

Kippenberg, T J; Spillane, S M; Armani, D K; Vahala, K J

2004-06-01

Using ultrahigh-Q toroid microcavities on a chip, we demonstrate a monolithic microcavity Raman laser. Cavity photon lifetimes in excess of 100 ns combined with mode volumes typically of less than 1000 (microm)3 significantly reduce the threshold for stimulated Raman scattering. In conjunction with the high ideality of a tapered optical fiber coupling junction, stimulated Raman lasing is observed at an ultralow threshold (as low as 74 microW of fiber-launched power at 1550 nm) with high efficiency (up to 45% at the critical coupling point) in good agreement with theoretical modeling. Equally important, the wafer-scale nature of these devices should permit integration with other photonic, mechanical, or electrical functionality on a chip.

Structural and functional characterization of the NHR1 domain of the Drosophila neuralized E3 ligase in the notch signaling pathway.

PubMed

He, Fahu; Saito, Kohei; Kobayashi, Naohiro; Harada, Takushi; Watanabe, Satoru; Kigawa, Takanori; Güntert, Peter; Ohara, Osamu; Tanaka, Akiko; Unzai, Satoru; Muto, Yutaka; Yokoyama, Shigeyuki

2009-10-23

The Notch signaling pathway is critical for many developmental processes and requires complex trafficking of both Notch receptor and its ligands, Delta and Serrate. In Drosophila melanogaster, the endocytosis of Delta in the signal-sending cell is essential for Notch receptor activation. The Neuralized protein from D. melanogaster (Neur) is a ubiquitin E3 ligase, which binds to Delta through its first neuralized homology repeat 1 (NHR1) domain and mediates the ubiquitination of Delta for endocytosis. Tom, a Bearded protein family member, inhibits the Neur-mediated endocytosis through interactions with the NHR1 domain. We have identified the domain boundaries of the novel NHR1 domain, using a screening system based on our cell-free protein synthesis method, and demonstrated that the identified Neur NHR1 domain had binding activity to the 20-residue peptide corresponding to motif 2 of Tom by isothermal titration calorimetry experiments. We also determined the solution structure of the Neur NHR1 domain by heteronuclear NMR methods, using a (15)N/(13)C-labeled sample. The Neur NHR1 domain adopts a characteristic beta-sandwich fold, consisting of a concave five-stranded antiparallel beta-sheet and a convex seven-stranded antiparallel beta-sheet. The long loop (L6) between the beta6 and beta7 strands covers the hydrophobic patch on the concave beta-sheet surface, and the Neur NHR1 domain forms a compact globular fold. Intriguingly, in spite of the slight, but distinct, differences in the topology of the secondary structure elements, the structure of the Neur NHR1 domain is quite similar to those of the B30.2/SPRY domains, which are known to mediate specific protein-protein interactions. Further NMR titration experiments of the Neur NHR1 domain with the 20-residue Tom peptide revealed that the resonances originating from the bottom area of the beta-sandwich (the L3, L5, and L11 loops, as well as the tip of the L6 loop) were affected. In addition, a structural comparison of the Neur NHR1 domain with the first NHR domain of the human KIAA1787 protein, which is from another NHR subfamily and does not bind to the 20-residue Tom peptide, suggested the critical amino acid residues for the interactions between the Neur NHR1 domain and the Tom peptide. The present structural study will shed light on the role of the Neur NHR1 domain in the Notch signaling pathway.

14C autoradiography with an energy-sensitive silicon pixel detector.

PubMed

Esposito, M; Mettivier, G; Russo, P

2011-04-07

The first performance tests are presented of a carbon-14 ((14)C) beta-particle digital autoradiography system with an energy-sensitive hybrid silicon pixel detector based on the Timepix readout circuit. Timepix was developed by the Medipix2 Collaboration and it is similar to the photon-counting Medipix2 circuit, except for an added time-based synchronization logic which allows derivation of energy information from the time-over-threshold signal. This feature permits direct energy measurements in each pixel of the detector array. Timepix is bump-bonded to a 300 µm thick silicon detector with 256 × 256 pixels of 55 µm pitch. Since an energetic beta-particle could release its kinetic energy in more than one detector pixel as it slows down in the semiconductor detector, an off-line image analysis procedure was adopted in which the single-particle cluster of hit pixels is recognized; its total energy is calculated and the position of interaction on the detector surface is attributed to the centre of the charge cluster. Measurements reported are detector sensitivity, (4.11 ± 0.03) × 10(-3) cps mm(-2) kBq(-1) g, background level, (3.59 ± 0.01) × 10(-5) cps mm(-2), and minimum detectable activity, 0.0077 Bq. The spatial resolution is 76.9 µm full-width at half-maximum. These figures are compared with several digital imaging detectors for (14)C beta-particle digital autoradiography.

Detection of critical cerebral desaturation thresholds by three regional oximeters during hypoxia: a pilot study in healthy volunteers.

PubMed

Tomlin, Kerry L; Neitenbach, Anna-Maria; Borg, Ulf

2017-01-13

Regional oximetry is increasingly used to monitor post-extraction oxygen status of the brain during surgical procedures where hemodynamic fluctuations are expected. Particularly in cardiac surgery, clinicians employ an interventional algorithm to restore baseline regional oxygen saturation (rSO 2 ) when a patient reaches a critical desaturation threshold. Evidence suggests that monitoring cardiac surgery patients and intervening to maintain rSO 2 can improve postoperative outcomes; however, evidence generated with one manufacturer's device may not be applicable to others. We hypothesized that regional oximeters from different manufacturers respond uniquely to changes in oxygen saturation in healthy volunteers. Three devices were tested: INVOS™ 5100C (Medtronic), EQUANOX™ 7600 (Nonin), and FORE-SIGHT™ (CASMED) monitors. We divided ten healthy subjects into two cohorts wearing a single sensor each from INVOS and EQUANOX (n = 6), or INVOS and FORE-SIGHT (n = 4). We induced and reversed hypoxia by adjusting the fraction of inspired oxygen. We calculated the magnitude of absolute rSO 2 change and rate of rSO 2 change during desaturation and resaturation, and determined if and when each device reached a critical interventional rSO 2 threshold during hypoxia. All devices responded to changes in oxygen directionally as expected. The median absolute rSO 2 change and the rate of rSO 2 change was significantly greater during desaturation and resaturation for INVOS compared with EQUANOX (P = 0.04). A similar but nonsignificant trend was observed for INVOS compared with FORE-SIGHT; our study was underpowered to definitively conclude there was no difference. A 10% relative decrease in rSO 2 during desaturation was detected by all three devices across the ten subjects. INVOS met a 20% relative decrease threshold in all subjects of both cohorts, compared to 1 with EQUANOX and 2 with FORE-SIGHT. Neither EQUANOX nor FORE-SIGHT reached a 50% absolute rSO 2 threshold compared with 4 and 3 subjects in each cohort with INVOS, respectively. Significant differences exist between the devices in how they respond to changes in oxygen saturation in healthy volunteers. We suggest caution when applying evidence generated with one manufacturer's device to all devices.

Nonlinear Upshift of Trapped Electron Mode Critical Density Gradient: Simulation and Experiment

NASA Astrophysics Data System (ADS)

Ernst, D. R.

2012-10-01

A new nonlinear critical density gradient for pure trapped electron mode (TEM) turbulence increases strongly with collisionality, saturating at several times the linear threshold. The nonlinear TEM threshold appears to limit the density gradient in new experiments subjecting Alcator C-Mod internal transport barriers to modulated radio-frequency heating. Gyrokinetic simulations show the nonlinear upshift of the TEM critical density gradient is associated with long-lived zonal flow dominated states [1]. This introduces a strong temperature dependence that allows external RF heating to control TEM turbulent transport. During pulsed on-axis heating of ITB discharges, core electron temperature modulations of 50% were produced. Bursts of line-integrated density fluctuations, observed on phase contrast imaging, closely follow modulations of core electron temperature inside the ITB foot. Multiple edge fluctuation measurements show the edge response to modulated heating is out of phase with the core response. A new limit cycle stability diagram shows the density gradient appears to be clamped during on-axis heating by the nonlinear TEM critical density gradient, rather than by the much lower linear threshold. Fluctuation wavelength spectra will be quantitatively compared with nonlinear TRINITY/GS2 gyrokinetic transport simulations, using an improved synthetic diagnostic. In related work, we are implementing the first gyrokinetic exact linearized Fokker Planck collision operator [2]. Initial results show short wavelength TEMs are fully stabilized by finite-gyroradius collisional effects for realistic collisionalities. The nonlinear TEM threshold and its collisionality dependence may impact predictions of density peaking based on quasilinear theory, which excludes zonal flows.[4pt] In collaboration with M. Churchill, A. Dominguez, C. L. Fiore, Y. Podpaly, M. L. Reinke, J. Rice, J. L. Terry, N. Tsujii, M. A. Barnes, I. Bespamyatnov, R. Granetz, M. Greenwald, A. Hubbard, J. W. Hughes, M. Landreman, B. Li, Y. Ma, P. Phillips, M. Porkolab, W. Rowan, S. Wolfe, and S. Wukitch.[4pt] [1] D. R. Ernst et al., Proc. 21st IAEA Fusion Energy Conference, Chengdu, China, paper IAEA-CN-149/TH/1-3 (2006). http://www-pub.iaea.org/MTCD/Meetings/FEC200/th1-3.pdf[0pt] [2] B. Li and D.R. Ernst, Phys. Rev. Lett. 106, 195002 (2011).

Response properties of mechanoreceptors and nociceptors in mouse glabrous skin: an in vivo study.

PubMed

Cain, D M; Khasabov, S G; Simone, D A

2001-04-01

The increasing use of transgenic mice for the study of pain mechanisms necessitates comprehensive understanding of the murine somatosensory system. Using an in vivo mouse preparation, we studied response properties of tibial nerve afferent fibers innervating glabrous skin. Recordings were obtained from 225 fibers identified by mechanical stimulation of the skin. Of these, 106 were classed as A beta mechanoreceptors, 51 as A delta fibers, and 68 as C fibers. A beta mechanoreceptors had a mean conduction velocity of 22.2 +/- 0.7 (SE) m/s (13.8--40.0 m/s) and a median mechanical threshold of 2.1 mN (0.4--56.6 mN) and were subclassed as rapidly adapting (RA, n = 75) or slowly adapting (SA, n = 31) based on responses to constant force mechanical stimuli. Conduction velocities ranged from 1.4 to 13.6 m/s (mean 7.1 +/- 0.6 m/s) for A delta fibers and 0.21 to 1.3 m/s (0.7 +/- 0.1 m/s) for C fibers. Median mechanical thresholds were 10.4 and 24.4 mN for A delta and C fibers, respectively. Responses of A delta and C fibers evoked by heat (35--51 degrees C) and by cold (28 to -12 degrees C) stimuli were determined. Mean response thresholds of A delta fibers were 42.0 +/- 3.1 degrees C for heat and 7.6 +/- 3.8 degrees C for cold, whereas mean response thresholds of C fibers were 40.3 +/- 0.4 degrees C for heat and 10.1 +/- 1.9 degrees C for cold. Responses evoked by heat and cold stimuli increased monotonically with stimulus intensity. Although only 12% of tested A delta fibers were heat sensitive, 50% responded to cold. Only one A delta nociceptor responded to both heat and cold stimuli. In addition, 40% of A delta fibers were only mechanosensitive since they responded neither to heat nor to cold stimuli. Thermal stimuli evoked responses from the majority of C fibers: 82% were heat sensitive, while 77% of C fibers were excited by cold, and 68% were excited by both heat and cold stimuli. Only 11% of C fibers were insensitive to heat and/or cold. This in vivo study provides an analysis of mouse primary afferent fibers innervating glabrous skin including new information on encoding of noxious thermal stimuli within the peripheral somatosensory system of the mouse. These results will be useful for future comparative studies with transgenic mice.

Distinct modes of gene regulation by a cell-specific transcriptional activator.

PubMed

Sengupta, Tanushri; Cohet, Nathalie; Morlé, François; Bieker, James J

2009-03-17

The architectural layout of a eukaryotic RNA polymerase II core promoter plays a role in general transcriptional activation. However, its role in tissue-specific expression is not known. For example, differing modes of its recognition by general transcription machinery can provide an additional layer of control within which a single tissue-restricted transcription factor may operate. Erythroid Kruppel-like factor (EKLF) is a hematopoietic-specific transcription factor that is critical for the activation of subset of erythroid genes. We find that EKLF interacts with TATA binding protein-associated factor 9 (TAF9), which leads to important consequences for expression of adult beta-globin. First, TAF9 functionally supports EKLF activity by enhancing its ability to activate the beta-globin gene. Second, TAF9 interacts with a conserved beta-globin downstream promoter element, and ablation of this interaction by beta-thalassemia-causing mutations decreases its promoter activity and disables superactivation. Third, depletion of EKLF prevents recruitment of TAF9 to the beta-globin promoter, whereas depletion of TAF9 drastically impairs beta-promoter activity. However, a TAF9-independent mode of EKLF transcriptional activation is exhibited by the alpha-hemoglobin-stabilizing protein (AHSP) gene, which does not contain a discernable downstream promoter element. In this case, TAF9 does not enhance EKLF activity and depletion of TAF9 has no effect on AHSP promoter activation. These studies demonstrate that EKLF directs different modes of tissue-specific transcriptional activation depending on the architecture of its target core promoter.

Convective instability in a porous enclosure with a horizontal conducting baffle

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

Chen, F.; Wang, C.Y.

1993-08-01

The study of heat transfer in a fluid-saturated porous medium is essential in a variety of practical situations, including thermal insulation design and geothermal energy utilization. The present paper studies the convective instability in a two-dimensional porous enclosure with a horizontal baffle protruding from one of the side walls. The vertical side walls are insulated, while the top and bottom surfaces are maintained at lower and higher constant temperatures, respectively. The present work considers a baffle of high conductivity. We assume the baffle temperature can be considered constant throughout. We ask, for a given enclosure aspect ratio, is the additionmore » of another physical constraint (such as lengthening a baffle) always stabilizing Is there an optimum baffle location and length such that the critical Rayleigh number is maximized In summary, several concluding remarks can be drawn in the following: (1) Other dimensions being same, a centered baffle always results in a more stable state than an off-centered baffle. (2) A full-length baffle, i.e., [beta]/[sigma] = 1, does not necessarily lead to greater stability. Instead, the value of ([beta]/[sigma])[sub max] is usually less than unity. For a centered baffle, the maximum R[sup c] occurs for [beta]/[sigma] [ge] ([beta]/[sigma])[sub max]; while for an off-centered baffle, the maximum R[sup c] occurs at ([beta]/[sigma])[sub max]. (3) The value of ([beta]/[sigma])[sub max] increases with [sigma]. 6 refs., 4 figs., 1 tab.« less

Critical gravitational collapse with angular momentum. II. Soft equations of state

NASA Astrophysics Data System (ADS)

Gundlach, Carsten; Baumgarte, Thomas W.

2018-03-01

We study critical phenomena in the collapse of rotating ultrarelativistic perfect fluids, in which the pressure P is related to the total energy density ρ by P =κ ρ , where κ is a constant. We generalize earlier results for radiation fluids with κ =1 /3 to other values of κ , focusing on κ <1 /9 . For 1 /9 <κ ≲0.49 , the critical solution has only one unstable, growing mode, which is spherically symmetric. For supercritical data it controls the black-hole mass, while for subcritical data it controls the maximum density. For κ <1 /9 , an additional axial l =1 mode becomes unstable. This controls either the black-hole angular momentum, or the maximum angular velocity. In theory, the additional unstable l =1 mode changes the nature of the black-hole threshold completely: at sufficiently large initial rotation rates Ω and sufficient fine-tuning of the initial data to the black-hole threshold we expect to observe nontrivial universal scaling functions (familiar from critical phase transitions in thermodynamics) governing the black-hole mass and angular momentum, and, with further fine-tuning, eventually a finite black-hole mass almost everywhere on the threshold. In practice, however, the second unstable mode grows so slowly that we do not observe this breakdown of scaling at the level of fine-tuning we can achieve, nor systematic deviations from the leading-order power-law scalings of the black-hole mass. We do see systematic effects in the black-hole angular momentum, but it is not clear yet if these are due to the predicted nontrivial scaling functions, or to nonlinear effects at sufficiently large initial angular momentum (which we do not account for in our theoretical model).

"Mind the gap!" Evaluation of the performance gap attributable to exception reporting and target thresholds in the new GMS contract: National database analysis.

PubMed

Fleetcroft, Robert; Steel, Nicholas; Cookson, Richard; Howe, Amanda

2008-06-17

The 2003 revision of the UK GMS contract rewards general practices for performance against clinical quality indicators. Practices can exempt patients from treatment, and can receive maximum payment for less than full coverage of eligible patients. This paper aims to estimate the gap between the percentage of maximum incentive gained and the percentage of patients receiving indicated care (the pay-performance gap), and to estimate how much of the gap is attributable respectively to thresholds and to exception reporting. Analysis of Quality Outcomes Framework data in the National Primary Care Database and exception reporting data from the Information Centre from 8407 practices in England in 2005 - 6. The main outcome measures were the gap between the percentage of maximum incentive gained and the percentage of patients receiving indicated care at the practice level, both for individual indicators and a combined composite score. An additional outcome was the percentage of that gap attributable respectively to exception reporting and maximum threshold targets set at less than 100%. The mean pay-performance gap for the 65 aggregated clinical indicators was 13.3% (range 2.9% to 48%). 52% of this gap (6.9% of eligible patients) is attributable to thresholds being set at less than 100%, and 48% to patients being exception reported. The gap was greater than 25% in 9 indicators: beta blockers and cholesterol control in heart disease; cholesterol control in stroke; influenza immunization in asthma; blood pressure, sugar and cholesterol control in diabetes; seizures in epilepsy and treatment of hypertension. Threshold targets and exception reporting introduce an incentive ceiling, which substantially reduces the percentage of eligible patients that UK practices need to treat in order to receive maximum incentive payments for delivering that care. There are good clinical reasons for exception reporting, but after unsuitable patients have been exempted from treatment, there is no reason why all maximum thresholds should not be 100%, whilst retaining the current lower thresholds to provide incentives for lower performing practices.

Utility of repeat testing of critical values: a Q-probes analysis of 86 clinical laboratories.

PubMed

Lehman, Christopher M; Howanitz, Peter J; Souers, Rhona; Karcher, Donald S

2014-06-01

A common laboratory practice is to repeat critical values before reporting the test results to the clinical care provider. This may be an unnecessary step that delays the reporting of critical test results without adding value to the accuracy of the test result. To determine the proportions of repeated chemistry and hematology critical values that differ significantly from the original value as defined by the participating laboratory, to determine the threshold differences defined by the laboratory as clinically significant, and to determine the additional time required to analyze the repeat test. Participants prospectively reviewed critical test results for 4 laboratory tests: glucose, potassium, white blood cell count, and platelet count. Participants reported the following information: initial and repeated test result; time initial and repeat results were first known to laboratory staff; critical result notification time; if the repeat result was still a critical result; if the repeat result was significantly different from the initial result, as judged by the laboratory professional or policy; significant difference threshold, as defined by the laboratory; the make and model of the instrument used for primary and repeat testing. Routine, repeat analysis of critical values is a common practice. Most laboratories did not formally define a significant difference between repeat results. Repeated results were rarely considered significantly different. Median repeated times were at least 17 to 21 minutes for 10% of laboratories. Twenty percent of laboratories reported at least 1 incident in the last calendar year of delayed result reporting that clinicians indicated had adversely affected patient care. Routine repeat analysis of automated chemistry and hematology critical values is unlikely to be clinically useful and may adversely affect patient care.

Measuring critical thinking in pre-registration midwifery students: A multi-method approach.

PubMed

Carter, Amanda G; Creedy, Debra K; Sidebotham, Mary

2018-02-01

Test the concurrent validity of three newly developed tools (student self-rating, preceptor rating, and reflective writing) that aim to measure critical thinking in midwifery practice. A descriptive matched cohort design was used. Australian research intensive university offering a three year Bachelor of Midwifery programme. Fifty-five undergraduate midwifery students. Students assessed their ability to apply critical thinking in midwifery practice using a 25-item tool and a 5-item subscale in Motivated Strategies for Learning Questionnaire. Clinical preceptors completed a 24-item tool assessing the students' application of critical thinking in practice. Reflective writing by students was assessed by midwifery academics using a 15-item tool. Internal reliability, and concurrent validity were assessed. Correlations, t-tests, multiple regression and confidence levels were calculated for the three scales and associations with student characteristics. The three scales achieved good internal reliability with a Cronbach's alpha coefficient between 0.93 and 0.97. Matched total scores for the three critical thinking scales were moderately correlated; student/preceptor (r=0.36, p<0.01); student/reflective writing (r=0.38, p<0.01); preceptor/reflective writing (r=0.30, p<0.05). All critical thinking mean scores were higher for students with a previous degree, but only significant for reflective writing (t (53)=-2.35, p=0.023). Preceptor ratings were predictive of GPA (beta=0.50, p<0.001, CI=0.10 to 0.30). Students' self-rating scores were predictive of year level (beta=0.32, p<0.05, CI=0.00 to 0.03). The student, preceptor, and reflective writing tools were found to be reliable and valid measures of critical thinking. The three tools can be used individually or in combination to provide students with various sources of feedback to improve their practice. The tools allow formative measurement of critical thinking over time. Further testing of the tools with larger, diverse samples is recommended. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons

PubMed Central

Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

2015-01-01

Dynamic spike threshold plays a critical role in neuronal input-output relations. In many neurons, the threshold potential depends on the rate of membrane potential depolarization (dV/dt) preceding a spike. There are two basic classes of neural excitability, i.e., Type I and Type II, according to input-output properties. Although the dynamical and biophysical basis of their spike initiation has been established, the spike threshold dynamic for each cell type has not been well described. Here, we use a biophysical model to investigate how spike threshold depends on dV/dt in two types of neuron. It is observed that Type II spike threshold is more depolarized and more sensitive to dV/dt than Type I. With phase plane analysis, we show that each threshold dynamic arises from the different separatrix and K+ current kinetics. By analyzing subthreshold properties of membrane currents, we find the activation of hyperpolarizing current prior to spike initiation is a major factor that regulates the threshold dynamics. The outward K+ current in Type I neuron does not activate at the perithresholds, which makes its spike threshold insensitive to dV/dt. The Type II K+ current activates prior to spike initiation and there is a large net hyperpolarizing current at the perithresholds, which results in a depolarized threshold as well as a pronounced threshold dynamic. These predictions are further attested in several other functionally equivalent cases of neural excitability. Our study provides a fundamental description about how intrinsic biophysical properties contribute to the threshold dynamics in Type I and Type II neurons, which could decipher their significant functions in neural coding. PMID:26083350

Critical validation studies of neurofeedback.

PubMed

Gruzelier, John; Egner, Tobias

2005-01-01

The field of neurofeedback training has proceeded largely without validation. In this article the authors review studies directed at validating sensory motor rhythm, beta and alpha-theta protocols for improving attention, memory, and music performance in healthy participants. Importantly, benefits were demonstrable with cognitive and neurophysiologic measures that were predicted on the basis of regression models of learning to enhance sensory motor rhythm and beta activity. The first evidence of operant control over the alpha-theta ratio is provided, together with remarkable improvements in artistic aspects of music performance equivalent to two class grades in conservatory students. These are initial steps in providing a much needed scientific basis to neurofeedback.

Critical energy flux and mass in solvable theories of 2D dilaton gravity

NASA Astrophysics Data System (ADS)

Fabbri, A.; Navarro-Salas, J.

1998-10-01

In this paper we address the issue of determining the semiclassical threshold for black hole formation in the context of a one-parameter family of theories which continuously interpolates between the RST and BPP models. We find that the results depend significantly on the initial static configuration of the spacetime geometry before the influx of matter is turned on. In some cases there is a critical energy density, given by the Hawking rate of evaporation, as well as a critical mass mcr (eventually vanishing). In others there is neither mcr nor a critical flux.

The glycan keratan sulfate in inner ear crystals

NASA Technical Reports Server (NTRS)

Fermin, C. D.; Martin, D. S.; Li, Y. T.; Li, S. C.

1995-01-01

The otoconial matrix (OM) of chicks (Gallus domesticus) inner ear was analyzed. Histochemically the OM was reacted with phosphotungstic acid (PTA) and immunohistochemically with the monoclonal antibody antikeratan sulfate (antiKS). The OM was digested with the enzyme endo-beta-galactosidase (E beta Galase) or separated by 1D and 2D gel electrophoresis. PTA which reacts with glycoproteins precipitated the OM, suggesting that the OM contains glycoproteins. A central core in each crystal had no PTA staining, suggesting that the core lacked glycoproteins. Anti KS antibody stained the OM with increased density in older embryos as determined by color thresholding. E beta Galase, which cleaves the lactosamine repeating units in KS, decreased the immunostain by 30% in the OM and by 20% in the cartilage. The OM from the utricle, saccule and macula lagena contained similar molecular weight bands. Five dense bands in the OM were less dense in tissue and blood controls, suggesting that such bands are enriched in the OM. Isoelectric focusing of the OM showed a negatively charged high molecular weight smear not present in blood and faint in tissue controls. The high affinity of the OM for the cationic PTA stain, the strong immunohistochemical reaction of the OM with anti KS antibody and high molecular weight negative smear in 2D gels taken together suggest that: a) the OM contains large amounts of glycoproteins and glycans, one of which is keratan sulfate, because its immuno stain with antiKS antibody was decreased by the enzyme E beta Galase, b) the utricle, saccule and macula lagena may have similar composition, and c) the concentration of KS may increase gradually until complete mineralization of the OM is reached.

Determination of {pi}{sup {+-}} meson polarizabilities from the {gamma}{gamma}{yields}{pi}{sup +}{pi}{sup -} process

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

Fil'kov, L.V.; Kashevarov, V.L.

2006-03-15

A fit of the experimental data to the total cross section of the process {gamma}{gamma}{yields}{pi}{sup +}{pi}{sup -} in the energy region from threshold to 2500 MeV has been carried out using dispersion relations with subtractions for the invariant amplitudes, where the dipole and the quadrupole polarizabilities of the charged pion are free parameters. As a result, the sum and the difference of the electric and magnetic dipole and quadrupole polarizabilities of the charged pion have been found: ({alpha}{sub 1}+{beta}{sub 1}){sub {pi}{sup {+-}}}=(0.18{sub -0.02}{sup +0.11})x10{sup -4} fm{sup 3},({alpha}{sub 1}-{beta}{sub 1}){sub {pi}{sup {+-}}}=(13.0{sub -1.9}{sup +2.6})x10{sup -4} fm{sup 3},({alpha}{sub 2}+{beta}{sub 2}){sub {pi}{sup {+-}}}=(0.133{+-}0.015)x10{supmore » -4} fm{sup 5},({alpha}{sub 2}-{beta}{sub 2}){sub {pi}{sup {+-}}}=(25.0{sub -0.3}{sup +0.8})x10{sup -4} fm{sup 5}. These values agree with the dispersion sum rule predictions. The value found for the difference of the dipole polarizabilities is consistent with the results obtained from scattering of high energy {pi}{sup -} mesons off the Coulomb field of heavy nuclei [Yu. M. Antipov et al., Phys. Lett. B121, 445 (1983)] and from radiative {pi}{sup +} photoproduction from the proton at MAMI [J. Ahrens et al., Eur. Phys. J. A 23, 113 (2005)], whereas it is at variance with the recent calculations in the framework of chiral perturbation theory.« less

Quantification of 19-nortestosterone sulphate and boldenone sulphate in urine from male horses using liquid chromatography/tandem mass spectrometry.

PubMed

Grace, Philip B; Drake, Erica C; Teale, Philip; Houghton, Edward

2008-10-01

Following administration of the anabolic steroid 19-nortestosterone or its esters to the horse, a major urinary metabolite is 19-nortestosterone-17beta-sulphate. The detection of 19-nortestosterone in urine from untreated animals has led to it being considered a naturally occurring steroid in the male horse. Recently, we have demonstrated that the majority of the 19-nortestosterone found in extracts of 'normal' urine from male horses arises as an artefact through decarboxylation of the 19-carboxylic acid of testosterone. The aim of this investigation was to establish if direct analysis of 19-nortestosterone-17beta-sulphate by liquid chromatography/tandem mass spectrometry (LC/MS/MS) had potential for the detection of 19-nortestosterone misuse in the male horse. The high concentrations of sulphate conjugates of the female sex hormones naturally present in male equine urine were overcome by selective hydrolysis of the aryl sulphates using glucuronidase from Helix pomatia; this was shown to have little or no activity for alkyl sulphates such as 19-nortestosterone-17beta-sulphate. The 'free' phenolic steroids were removed by solid-phase extraction (SPE) prior to LC/MS/MS analysis. The method also allowed for the quantification of the sulphate conjugate of boldenone, a further anabolic steroid endogenous in the male equine with potential for abuse in sports. The method was applied to the quantification of these analytes in a population of samples. This paper reports the results of that study along with the development and validation of the LC/MS/MS method. The results indicate that while 19-nortestosterone-17beta-sulphate is present at low levels as an endogenous substance in urine from 'normal' male horses, its use as an effective threshold substance may be viable.

Isolation, characterization, and purification to homogeneity of an endogenous polypeptide with agonistic action on benzodiazepine receptors.

PubMed Central

Guidotti, A; Forchetti, C M; Corda, M G; Konkel, D; Bennett, C D; Costa, E

1983-01-01

A brain polypeptide termed diazepam-binding inhibitor (DBI) and thought to be chemically and functionally related to the endogenous effector of the benzodiazepine recognition site was purified to homogeneity. This peptide gives a single band of protein on NaDodSO4 and acidic urea gel electrophoresis. A single UV-absorbing peak was obtained by HPLC using three different columns and solvent systems. DBI has a molecular mass of approximately equal to 11,000 daltons. Carboxyl-terminus analysis shows that tyrosine is the only residue while the amino-terminus was blocked. Cyanogen bromide treatment of DBI yields three polypeptide fragments, and the sequences of two of them have been determined for a total of 45 amino acids. DBI is a competitive inhibitor for the binding of [3H]diazepam, [3H]flunitrazepam, beta-[3H]carboline propyl esters, and 3H-labeled Ro 15-1788. The Ki for [3H]-diazepam and beta-[3H]carboline binding were 4 and 1 microM, respectively. Doses of DBI that inhibited [3H]diazepam binding by greater than 50% fail to change [3H]etorphine, gamma-amino[3H]butyric acid, [3H]-quinuclidinyl benzilate, [3H]dihydroalprenolol, [3H]adenosine, and [3H]imipramine binding tested at their respective Kd values. DBI injected intraventricularly at doses of 5-10 nmol completely reversed the anticonflict action of diazepam on unpunished drinking and, similar to the anxiety-inducing beta-carboline derivative FG 7142 (beta-carboline-3-carboxylic acid methyl ester), facilitated the shock-induced suppression of drinking by lowering the threshold for this response. Images PMID:6304714

Regulatory T cells protect mice against coxsackievirus-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway.

PubMed

Shi, Yu; Fukuoka, Masahiro; Li, Guohua; Liu, Youan; Chen, Manyin; Konviser, Michael; Chen, Xin; Opavsky, Mary Anne; Liu, Peter P

2010-06-22

Coxsackievirus B3 infection is an excellent model of human myocarditis and dilated cardiomyopathy. Cardiac injury is caused either by a direct cytopathic effect of the virus or through immune-mediated mechanisms. Regulatory T cells (Tregs) play an important role in the negative modulation of host immune responses and set the threshold of autoimmune activation. This study was designed to test the protective effects of Tregs and to determine the underlying mechanisms. Carboxyfluorescein diacetate succinimidyl ester-labeled Tregs or naïve CD4(+) T cells were injected intravenously once every 2 weeks 3 times into mice. The mice were then challenged with intraperitoneal coxsackievirus B3 immediately after the last cell transfer. Transfer of Tregs showed higher survival rates than transfer of CD4(+) T cells (P=0.0136) but not compared with the PBS injection group (P=0.0589). Interestingly, Tregs also significantly decreased virus titers and inflammatory scores in the heart. Transforming growth factor-beta and phosphorylated AKT were upregulated in Tregs-transferred mice and coxsackie-adenovirus receptor expression was decreased in the heart compared with control groups. Transforming growth factor-beta decreased coxsackie-adenovirus receptor expression and inhibited coxsackievirus B3 infection in HL-1 cells and neonatal cardiac myocytes. Splenocytes collected from Treg-, CD4(+) T-cell-, and PBS-treated mice proliferated equally when stimulated with heat-inactivated virus, whereas in the Treg group, the proliferation rate was reduced significantly when stimulated with noninfected heart tissue homogenate. Adoptive transfer of Tregs protected mice from coxsackievirus B3-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway and thus suppresses the immune response to cardiac tissue, maintaining the antiviral immune response.

A high performance sensorimotor beta rhythm-based brain computer interface associated with human natural motor behavior

NASA Astrophysics Data System (ADS)

Bai, Ou; Lin, Peter; Vorbach, Sherry; Floeter, Mary Kay; Hattori, Noriaki; Hallett, Mark

2008-03-01

To explore the reliability of a high performance brain-computer interface (BCI) using non-invasive EEG signals associated with human natural motor behavior does not require extensive training. We propose a new BCI method, where users perform either sustaining or stopping a motor task with time locking to a predefined time window. Nine healthy volunteers, one stroke survivor with right-sided hemiparesis and one patient with amyotrophic lateral sclerosis (ALS) participated in this study. Subjects did not receive BCI training before participating in this study. We investigated tasks of both physical movement and motor imagery. The surface Laplacian derivation was used for enhancing EEG spatial resolution. A model-free threshold setting method was used for the classification of motor intentions. The performance of the proposed BCI was validated by an online sequential binary-cursor-control game for two-dimensional cursor movement. Event-related desynchronization and synchronization were observed when subjects sustained or stopped either motor execution or motor imagery. Feature analysis showed that EEG beta band activity over sensorimotor area provided the largest discrimination. With simple model-free classification of beta band EEG activity from a single electrode (with surface Laplacian derivation), the online classifications of the EEG activity with motor execution/motor imagery were: >90%/~80% for six healthy volunteers, >80%/~80% for the stroke patient and ~90%/~80% for the ALS patient. The EEG activities of the other three healthy volunteers were not classifiable. The sensorimotor beta rhythm of EEG associated with human natural motor behavior can be used for a reliable and high performance BCI for both healthy subjects and patients with neurological disorders. Significance: The proposed new non-invasive BCI method highlights a practical BCI for clinical applications, where the user does not require extensive training.