Science.gov

Sample records for partially irreversible inactivation

  1. Preventing Scars after Injury with Partial Irreversible Electroporation.

    PubMed

    Golberg, Alexander; Villiger, Martin; Khan, Saiqa; Quinn, Kyle P; Lo, William C Y; Bouma, Brett E; Mihm, Martin C; Austen, William G; Yarmush, Martin L

    2016-11-01

    Preventing the formation of hypertrophic scars, especially those that are a result of major trauma or burns, would have enormous impact in the fields of regenerative and trauma medicine. In this report, we introduce a noninvasive method to prevent scarring based on nonthermal partial irreversible electroporation. Contact burn injuries in rats were treated with varying treatment parameters to optimize the treatment protocol. Scar surface area and structural properties of the scar were assessed with histology and non-invasive, longitudinal imaging with polarization-sensitive optical coherence tomography. We found that partial irreversible electroporation using 200 pulses of 250 V and 70 μs duration, delivered at 3 Hz every 20 days during a total of five therapy sessions after the initial burn injury, resulted in a 57.9% reduction of the scar area compared with untreated scars and structural features approaching those of normal skin. Unlike humans, rats do not develop hypertrophic scars. Therefore, the use of a rat animal model is the limiting factor of this work.

  2. Penicillanic acid sulfone: nature of irreversible inactivation of RTEM beta-lactamase from Escherichia coli.

    PubMed

    Brenner, D G; Knowles, J R

    1984-11-20

    When penicillanic acid sulfone in large molar excess is incubated with the RTEM beta-lactamase, the enzyme becomes inactivated irreversibly. From studies of the consequential spectroscopic changes, from the use of specifically tritiated penicillanic acid sulfone, and from comparison by isoelectric focusing of the enzyme after inactivation by the sulfone and by clavulanic acid, the inactivated enzyme appears to be cross-linked by a beta-aminoacrylate fragment deriving from C-5, C-6, and C-7 of the original beta-lactam. Model studies on the behavior of alcoholic solutions of penicillanic acid sulfone in the presence of amines are entirely consistent with this interpretation.

  3. Mildly Acidic pH Triggers an Irreversible Conformational Change in the Fusion Domain of Herpes Simplex Virus 1 Glycoprotein B and Inactivation of Viral Entry.

    PubMed

    Weed, Darin J; Pritchard, Suzanne M; Gonzalez, Floricel; Aguilar, Hector C; Nicola, Anthony V

    2017-03-01

    Herpes simplex virus (HSV) entry into a subset of cells requires endocytosis and endosomal low pH. Preexposure of isolated virions to mildly acidic pH of 5 to 6 partially inactivates HSV infectivity in an irreversible manner. Acid inactivation is a hallmark of viruses that enter via low-pH pathways; this occurs by pretriggering conformational changes essential for fusion. The target and mechanism(s) of low-pH inactivation of HSV are unclear. Here, low-pH-treated HSV-1 was defective in fusion activity and yet retained normal levels of attachment to cell surface heparan sulfate and binding to nectin-1 receptor. Low-pH-triggered conformational changes in gB reported to date are reversible, despite irreversible low-pH inactivation. gB conformational changes and their reversibility were measured by antigenic analysis with a panel of monoclonal antibodies and by detecting changes in oligomeric conformation. Three-hour treatment of HSV-1 virions with pH 5 or multiple sequential treatments at pH 5 followed by neutral pH caused an irreversible >2.5 log infectivity reduction. While changes in several gB antigenic sites were reversible, alteration of the H126 epitope was irreversible. gB oligomeric conformational change remained reversible under all conditions tested. Altogether, our results reveal that oligomeric alterations and fusion domain changes represent distinct conformational changes in gB, and the latter correlates with irreversible low-pH inactivation of HSV. We propose that conformational change in the gB fusion domain is important for activation of membrane fusion during viral entry and that in the absence of a host target membrane, this change results in irreversible inactivation of virions.IMPORTANCE HSV-1 is an important pathogen with a high seroprevalence throughout the human population. HSV infects cells via multiple pathways, including a low-pH route into epithelial cells, the primary portal into the host. HSV is inactivated by low-pH preexposure, and gB, a

  4. Pulsed electric field inactivation of diarrhoeagenic Bacillus cereus through irreversible electroporation.

    PubMed

    Rowan, N J; MacGregor, S J; Anderson, J G; Fouracre, R A; Farish, O

    2000-08-01

    The physical effects of high-intensity pulsed electric fields (PEF) on the inactivation of diarrhoeagenic Bacillus cereus cells suspended in 0.1% peptone water were examined by transmission electron microscopy (TEM). The levels of PEF-induced microbial cell death were determined by enumeration on tryptone soy yeast extract agar and Bacillus cereus-selective agar plates. Following exposure to lethal levels of PEF, TEM investigation revealed irreversible cell membrane rupture at a number of locations, with the apparent leakage of intracellular contents. This study provides a clearer understanding of the mechanism of PEF-induced cellular damage, information that is essential for the further optimization of this emerging food-processing technology.

  5. Peptides containing acylated C-terminal gem diamines: novel irreversible inactivators of the cysteine and serine proteinases.

    PubMed

    Gilmore, B F; Lynas, J F; Harriott, P; Healy, A; Walker, B

    2006-05-01

    This study reports on the synthesis of peptides containing C-terminal acylated gem-diamines and their utilization for the preparation of irreversible inactivators of the serine and cysteine proteinases. We have succeeded in obtaining an inhibitor Acetyl-Val-Pro-g-Val-CO-O-C(6)H(4)-NO(2) of neutrophil and pancreatic elastases that functions in a time-dependent manner, indicative of the action of an irreversible inactivator, functioning, most probably, through the formation of a long-lived acyl enzyme intermediate. In addition, we have demonstrated the irreversible inhibition of the cysteine proteinase bovine cathepsin B, by chloroacetyl and bromoacetyl derivatives of a dipeptide gem-diamine, Cbz-Phe-g-Ala-CO-CH(2)Hal (Hal = Br, Cl).

  6. Irreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methylarginine requires NADPH-dependent hydroxylation.

    PubMed

    Feldman, P L; Griffith, O W; Hong, H; Stuehr, D J

    1993-02-19

    L-NG-Methylarginine (NMA) is an established mechanism-based inactivator of murine macrophage nitric oxide synthase (mNOS). In this report, NMA is shown to irreversibly inhibit both mNOS (k(inact) = 0.08 min-1) and the recombinant constitutive brain NOS (bNOS). For both NOS isoforms, metabolism of NMA parallels that of the natural substrate L-arginine (ARG), in that it undergoes a regiospecific, NADPH-dependent hydroxylation to form L-NG-hydroxy-NG-methylarginine (NOHNMA). This intermediate then undergoes further NADPH-dependent oxidation to form L-citrulline (CIT). Authentic NOHNMA, synthesized from L-ornithine, irreversibly inhibited both mNOS (k(inact) = 0.10 min-1) and bNOS in an NADPH-dependent reaction. The conversion of either NMA or NOHNMA to CIT correlated with irreversible enzyme inactivation. Thus, the data suggest that enzyme inhibition occurs as a consequence of oxidative metabolism of the intermediate, NOHNMA. A unified mechanism is proposed that accounts for NO biosynthesis from ARG, for the inactivation of NOS by NMA and for the intermediacy of hydroxylated ARG or NMA derivatives in these processes.

  7. Reversible, partial inactivation of plant betaine aldehyde dehydrogenase by betaine aldehyde: mechanism and possible physiological implications.

    PubMed

    Zárate-Romero, Andrés; Murillo-Melo, Darío S; Mújica-Jiménez, Carlos; Montiel, Carmina; Muñoz-Clares, Rosario A

    2016-04-01

    In plants, the last step in the biosynthesis of the osmoprotectant glycine betaine (GB) is the NAD(+)-dependent oxidation of betaine aldehyde (BAL) catalysed by some aldehyde dehydrogenase (ALDH) 10 enzymes that exhibit betaine aldehyde dehydrogenase (BADH) activity. Given the irreversibility of the reaction, the short-term regulation of these enzymes is of great physiological relevance to avoid adverse decreases in the NAD(+):NADH ratio. In the present study, we report that the Spinacia oleracea BADH (SoBADH) is reversibly and partially inactivated by BAL in the absence of NAD(+)in a time- and concentration-dependent mode. Crystallographic evidence indicates that the non-essential Cys(450)(SoBADH numbering) forms a thiohemiacetal with BAL, totally blocking the productive binding of the aldehyde. It is of interest that, in contrast to Cys(450), the catalytic cysteine (Cys(291)) did not react with BAL in the absence of NAD(+) The trimethylammonium group of BAL binds in the same position in the inactivating or productive modes. Accordingly, BAL does not inactivate the C(450)SSoBADH mutant and the degree of inactivation of the A(441)I and A(441)C mutants corresponds to their very different abilities to bind the trimethylammonium group. Cys(450)and the neighbouring residues that participate in stabilizing the thiohemiacetal are strictly conserved in plant ALDH10 enzymes with proven or predicted BADH activity, suggesting that inactivation by BAL is their common feature. Under osmotic stress conditions, this novel partial and reversible covalent regulatory mechanism may contribute to preventing NAD(+)exhaustion, while still permitting the synthesis of high amounts of GB and avoiding the accumulation of the toxic BAL.

  8. Irreversible APC(Cdh1) Inactivation Underlies the Point of No Return for Cell-Cycle Entry.

    PubMed

    Cappell, Steven D; Chung, Mingyu; Jaimovich, Ariel; Spencer, Sabrina L; Meyer, Tobias

    2016-06-30

    Proliferating cells must cross a point of no return before they replicate their DNA and divide. This commitment decision plays a fundamental role in cancer and degenerative diseases and has been proposed to be mediated by phosphorylation of retinoblastoma (Rb) protein. Here, we show that inactivation of the anaphase-promoting complex/cyclosome (APC(Cdh1)) has the necessary characteristics to be the point of no return for cell-cycle entry. Our study shows that APC(Cdh1) inactivation is a rapid, bistable switch initiated shortly before the start of DNA replication by cyclin E/Cdk2 and made irreversible by Emi1. Exposure to stress between Rb phosphorylation and APC(Cdh1) inactivation, but not after APC(Cdh1) inactivation, reverted cells to a mitogen-sensitive quiescent state, from which they can later re-enter the cell cycle. Thus, APC(Cdh1) inactivation is the commitment point when cells lose the ability to return to quiescence and decide to progress through the cell cycle.

  9. Irreversible inactivation of interleukin 2 in a pump-based delivery environment.

    PubMed Central

    Tzannis, S T; Hrushesky, W J; Wood, P A; Przybycien, T M

    1996-01-01

    The physical stability of pharmaceutical proteins in delivery environments is a critical determinant of biological potency and treatment efficacy, and yet it is often taken for granted. We studied both the bioactivity and physical stability of interleukin 2 upon delivery via continuous infusion. We found that the biological activity of the delivered protein was dramatically reduced by approximately 90% after a 24-hr infusion program. Only a portion of these losses could be attributed to direct protein deposition on the delivery surfaces. Analysis of delivered protein by size exclusion chromatography gave no indication of insulin-like, surface-induced aggregation phenomena. Examination of the secondary and tertiary structure of both adsorbed and delivered protein via Fourier-transform infrared spectroscopy, circular dichroism, and fluorescence spectroscopy indicated that transient surface association of interleukin 2 with the catheter tubing resulted in profound, irreversible structural changes that were responsible for the majority of the biological activity losses. PMID:8643597

  10. Irreversible inactivation of interleukin 2 in a pump-based delivery environment.

    PubMed

    Tzannis, S T; Hrushesky, W J; Wood, P A; Przybycien, T M

    1996-05-28

    The physical stability of pharmaceutical proteins in delivery environments is a critical determinant of biological potency and treatment efficacy, and yet it is often taken for granted. We studied both the bioactivity and physical stability of interleukin 2 upon delivery via continuous infusion. We found that the biological activity of the delivered protein was dramatically reduced by approximately 90% after a 24-hr infusion program. Only a portion of these losses could be attributed to direct protein deposition on the delivery surfaces. Analysis of delivered protein by size exclusion chromatography gave no indication of insulin-like, surface-induced aggregation phenomena. Examination of the secondary and tertiary structure of both adsorbed and delivered protein via Fourier-transform infrared spectroscopy, circular dichroism, and fluorescence spectroscopy indicated that transient surface association of interleukin 2 with the catheter tubing resulted in profound, irreversible structural changes that were responsible for the majority of the biological activity losses.

  11. Pilot Study to Assess Safety and Clinical Outcomes of Irreversible Electroporation for Partial Gland Ablation in Men with Prostate Cancer

    PubMed Central

    Murray, Katie S.; Ehdaie, Behfar; Musser, John; Mashni, Joseph; Srimathveeravalli, Govindarajan; Durack, Jeremy C.; Solomon, Stephen B.; Coleman, Jonathan A.

    2016-01-01

    Purpose Partial prostate gland ablation is a strategy to manage localized prostate cancer. Irreversible electroporation can ablate localized soft tissues. We sought to describe 30- and 90-day complications and intermediate-term functional outcomes in men undergoing prostate gland ablation using irreversible electroporation. Materials and Methods We reviewed the charts of 25 patients with prostate cancer who underwent prostate gland ablation using irreversible electroporation as a primary procedure and who were followed for at least 6 months. Results Median follow-up was 10.9 months. Grade 3 complications occurred in 2 patients including epididymitis (1) and urinary tract infection (1). Fourteen patients experienced grade ≤ 2 complications, mainly transient urinary symptoms, hematuria, and urinary tract infections. Of 25 patients, 4 (16%) had cancer in the zone of ablation on routine follow-up biopsy at 6 months. Of those with normal urinary function at baseline, 88% and 94% reported normal urinary function at 6 and 12 months after prostate gland ablation, respectively. By 12 months, only 1 patient with normal erectile function at baseline reported new difficulty with potency and only 2 patients (8%) required a pad for urinary incontinence. Conclusions Prostate gland ablation with irreversible electroporation is feasible and safe in selected men with localized prostate cancer. Intermediate-term urinary and erectile function outcomes appear reasonable. Irreversible electroporation is effective in ablation of tumor-bearing prostate tissue, as a majority of men had no evidence of residual cancer on biopsy 6 months after prostate gland ablation. PMID:27113966

  12. Irreversible conversion of the physical state of herpes simplex virus preceding inactivation by thermal or antibody treatment

    SciTech Connect

    Yanagi, K.

    1981-05-01

    The buoyant density characteristics of infectious particles of herpes simplex virus types 1 and 2 were studied by centrifugation in sucrose and cesium chloride density gradients with a high resolution and satisfactory infectivity recovery. It was shown that two populations of infectious virions differing in buoyant density coexisted, the difference being slight but definite. The ratio of heavy (H) to light (L) viral particles varied depending upon the solute used, the strains of virus, and the cell origin. Circumstances favoring degradation of viral infectivity tended to increase the H portion. Incubation at 37 degrees C largely converted L to H, and heating at 45 degrees C converted all virions to H without infectivity. The L to H conversion was irreversible, and no populations intermediate between L and H were clearly observed. Inactivation by UV light irradiation did not affect the density pattern. That H was not an artefact due to penetration of solutes, osmotic pressure, viral aggregation, or loss of the envelope was shown experimentally. A difference in the outer shape of particles between negatively stained L and H populations was demonstrated by electron microscopy. Both cell-released and cell-bound herpes simplex virus particles gave essentially the same result with respect to the above characteristics. The effect of limiting dilutions of antiserum was similar to that of mild thermal treatment, in that denser virions increased parallel to a decrease in less dense virions. Sensitization with early immunoglobulin G, composed mainly of complement-requiring neutralizing antibody, caused the density transition, and subsequent addition of complement resulted in a further increase in the buoyant density of the sensitized virions.

  13. Partial purification of the mu opioid receptor irreversibly labeled with (/sup 3/H)b-funaltrexamine

    SciTech Connect

    Liu-Chen, L.Y.; Phillips, C.A.; Tam, S.W.

    1986-03-01

    The mu opioid receptor in bovine striatal membranes was specifically and irreversibly labeled by incubation with 5 nM (/sup 3/H)..beta..-funaltrexamine (approx.-FNA) at 37/sup 0/C for 90 min in the presence of 100 mM NaCl. The specific and irreversible binding of (/sup 3/H)..beta..-FNA as defined by that blocked by 1 /sup +/M naloxone was about 60% of total irreversible binding. The specific irreversible binding was saturable, stereospecific, time-, temperature, and tissue-dependent. Mu opioid ligands were much more potent than delta or kappa ligands in inhibiting the specific irreversible labeling. SDS polyacrylamide gel electrophoresis of solubilized membranes in the presence of 2-mercaptoethanol yielded a major radiolabeled broad band of MW 68-97K daltons, characteristic of a glycoprotein band. This band was not observed in membranes labeled in the presence of excess unlabeled naloxone. The glycoprotein nature of the (/sup 3/H)..beta..-FNA-labeled opioid receptor was confirmed by its binding to a wheat germ agglutinin-Sepharose column and its elution with N-acetylglucosamine.

  14. Inactivation of arginine esterase E-I of Bitis gabonica venom by irreversible inhibitors including a water-soluble carbodiimide, a chloromethyl ketone and isatoic anhydride.

    PubMed

    Gravett, P S; Viljoen, C C; Oosthuizen, M M

    1991-01-01

    1. Esterase E-I from Bitis gabonica was inactivated with irreversible inhibitors which included studies with a water-soluble carbodiimide, an affinity labelling peptide and a mechanism-based inactivator. 2. The reaction with 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide was biphasic and the dominant part followed saturation kinetics. At pH 5.5 a rate constant of 0.4 min-1 for inactive enzyme formation was calculated and a dissociation constant (Ki) of 0.2 M for the enzyme-inhibitor complex. 3. Inactivation with D-Phe-Pro-Arg-chloromethyl ketone indicated a two-step mechanism, for which the reaction parameters at pH 8.0 were determined. The Ki value was 0.2 microM and the inactivation rate was 2.5 min-1. 4. With isatoic anhydride pseudo-first-order kinetics was observed. At pH 8.0 a rate constant of 0.9 min-1 and a Ki of 2.0 mM were obtained. The inactivation of the enzyme was found to be governed by a group in the enzyme showing a pK value of 7.3.

  15. Characterization of CM572, a Selective Irreversible Partial Agonist of the Sigma-2 Receptor with Antitumor Activity.

    PubMed

    Nicholson, Hilary; Comeau, Anthony; Mesangeau, Christophe; McCurdy, Christopher R; Bowen, Wayne D

    2015-08-01

    The sigma-2 receptors are promising therapeutic targets because of their significant upregulation in tumor cells compared with normal tissue. Here, we characterize CM572 [3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)-6-isothiocyanatobenzo[d]oxazol-2(3H)-one] (sigma-1 Ki ≥ 10 µM, sigma-2 Ki = 14.6 ± 6.9 nM), a novel isothiocyanate derivative of the putative sigma-2 antagonist, SN79 [6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one]. CM572 bound irreversibly to sigma-2 receptors by virtue of the isothiocyanate moiety but not to sigma-1. Studies in human SK-N-SH neuroblastoma cells revealed that CM572 induced an immediate dose-dependent increase in cytosolic calcium concentration. A 24-hour treatment of SK-N-SH cells with CM572 induced dose-dependent cell death, with an EC50 = 7.6 ± 1.7 µM. This effect was sustained over 24 hours even after a 60-minute pretreatment with CM572, followed by extensive washing to remove ligand, indicating an irreversible effect consistent with the irreversible binding data. Western blot analysis revealed that CM572 also induced cleavage activation of proapoptotic BH3-interacting domain death agonist. These data suggest irreversible agonist-like activity. Low concentrations of CM572 that were minimally effective were able to attenuate significantly the calcium signal and cell death induced by the sigma-2 agonist CB-64D [(+)-1R,5R-(E)-8-benzylidene-5-(3-hydroxyphenyl)-2-methylmorphan-7-one]. CM572 was also cytotoxic against PANC-1 pancreatic and MCF-7 breast cancer cell lines. The cytotoxic activity of CM572 was selective for cancer cells over normal cells, being much less potent against primary human melanocytes and human mammary epithelial cells. Taken together, these data show that CM572 is a selective, irreversible sigma-2 receptor partial agonist. This novel irreversible ligand may further our understanding of the endogenous role of this receptor, in addition to having potential use in targeted

  16. Characterization of CM572, a Selective Irreversible Partial Agonist of the Sigma-2 Receptor with Antitumor Activity

    PubMed Central

    Nicholson, Hilary; Comeau, Anthony; Mesangeau, Christophe; McCurdy, Christopher R.

    2015-01-01

    The sigma-2 receptors are promising therapeutic targets because of their significant upregulation in tumor cells compared with normal tissue. Here, we characterize CM572 [3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)-6-isothiocyanatobenzo[d]oxazol-2(3H)-one] (sigma-1 Ki ≥ 10 µM, sigma-2 Ki = 14.6 ± 6.9 nM), a novel isothiocyanate derivative of the putative sigma-2 antagonist, SN79 [6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one]. CM572 bound irreversibly to sigma-2 receptors by virtue of the isothiocyanate moiety but not to sigma-1. Studies in human SK-N-SH neuroblastoma cells revealed that CM572 induced an immediate dose-dependent increase in cytosolic calcium concentration. A 24-hour treatment of SK-N-SH cells with CM572 induced dose-dependent cell death, with an EC50 = 7.6 ± 1.7 µM. This effect was sustained over 24 hours even after a 60-minute pretreatment with CM572, followed by extensive washing to remove ligand, indicating an irreversible effect consistent with the irreversible binding data. Western blot analysis revealed that CM572 also induced cleavage activation of proapoptotic BH3-interacting domain death agonist. These data suggest irreversible agonist-like activity. Low concentrations of CM572 that were minimally effective were able to attenuate significantly the calcium signal and cell death induced by the sigma-2 agonist CB-64D [(+)-1R,5R-(E)-8-benzylidene-5-(3-hydroxyphenyl)-2-methylmorphan-7-one]. CM572 was also cytotoxic against PANC-1 pancreatic and MCF-7 breast cancer cell lines. The cytotoxic activity of CM572 was selective for cancer cells over normal cells, being much less potent against primary human melanocytes and human mammary epithelial cells. Taken together, these data show that CM572 is a selective, irreversible sigma-2 receptor partial agonist. This novel irreversible ligand may further our understanding of the endogenous role of this receptor, in addition to having potential use in targeted

  17. Active site directed irreversible inactivation of brewers' yeast pyruvate decarboxylase by the conjugated substrate analogue (E)-4-(4-chlorophenyl)-2-oxo-3-butenoic acid: development of a suicide substrate.

    PubMed

    Kuo, D J; Jordan, F

    1983-08-02

    (E)-4-(4-Chlorophenyl)-2-oxo-3-butenoic acid (CPB) was found to irreversibly inactivate brewers' yeast pyruvate decarboxylase (PDC, EC 4.1.1.1) in a biphasic, sigmoidal manner, as is found for the kinetic behavior of substrate. An expression was derived for two-site irreversible inhibition of allosteric enzymes, and the kinetic behavior of CPB fit the expression for two-site binding. The calculated Ki's of 0.7 mM and 0.3 mM for CPB were assigned to the catalytic site and the regulatory site, respectively. The presence of pyruvic acid at high concentrations protected PDC from inactivation, whereas low concentrations of pyruvic acid accelerated inactivation by CPB. Pyruvamide, a known allosteric activator of PDC, was found to enhance inactivation by CPB. The results can be explained if pyruvamide binds only to a regulatory site, but CPB and pyruvic acid compete for both the regulatory and the catalytic centers. [1-14C]CPB was found to lose 14CO2 concurrently with the inactivation of the enzyme. Therefore, CPB was being turned over by PDC, in addition to inactivating it. CPB can be labeled a suicide-type inactivator for PDC.

  18. Partial hydrogenation induced interaction in a graphene-SiO2 interface: irreversible modulation of device characteristics.

    PubMed

    Iwasaki, Takuya; Muruganathan, Manoharan; Schmidt, Marek E; Mizuta, Hiroshi

    2017-01-26

    The transformation of systematic vacuum and hydrogen annealing effects in graphene devices on the SiO2 surface is reported based on experimental and van der Waals interaction corrected density functional theory (DFT) simulation results. Vacuum annealing removes p-type dopants and reduces charged impurity scattering in graphene. Moreover, it induces n-type doping into graphene, leading to the improvement of the electron mobility and conductivity in the electron transport regime, which are reversed by exposing to atmospheric environment. On the other hand, annealing in hydrogen/argon gas results in smaller n-type doping along with a decrease in the overall conductivity and carrier mobility. This degradation of the conductivity is irreversible even the graphene devices are exposed to ambience. This was clarified by DFT simulations: initially, silicon dangling bonds were partially terminated by hydrogen, subsequently, the remaining dangling bonds became active and the distance between the graphene and SiO2 surface decreased. Moreover, both annealing methods affect the graphene channel including the vicinity of the metal contacts, which plays an important role in asymmetric carrier transport.

  19. Interactions of peptide triazole thiols with Env gp120 induce irreversible breakdown and inactivation of HIV-1 virions

    PubMed Central

    2013-01-01

    Background We examined the underlying mechanism of action of the peptide triazole thiol, KR13 that has been shown previously to specifically bind gp120, block cell receptor site interactions and potently inhibit HIV-1 infectivity. Results KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein release. The resulting virion post virolysis had an altered morphology, contained no gp120, but retained gp41 that bound to neutralizing gp41 antibodies. Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks formation of the gp41 6-helix bundle during membrane fusion, while no inhibition of p24 release occurred for enfuvirtide-resistant virus. KR13 thus appears to induce structural changes in gp41 normally associated with membrane fusion and cell entry. The HIV-1 p24 release induced by KR13 was observed in several clades of HIV-1 as well as in fully infectious HIV-1 virions. Conclusions The antiviral activity of KR13 and its ability to inactivate virions prior to target cell engagement suggest that peptide triazole thiols could be highly effective in inhibiting HIV transmission across mucosal barriers and provide a novel probe to understand biochemical signals within envelope that are involved in membrane fusion. PMID:24330857

  20. Pharmacokinetics and Disposition of the Thiouracil Derivative PF-06282999, an Orally Bioavailable, Irreversible Inactivator of Myeloperoxidase Enzyme, Across Animals and Humans.

    PubMed

    Dong, Jennifer Q; Varma, Manthena V; Wolford, Angela; Ryder, Tim; Di, Li; Feng, Bo; Terra, Steven G; Sagawa, Kazuko; Kalgutkar, Amit S

    2016-02-01

    The thiouracil derivative PF-06282999 [2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide] is an irreversible inactivator of myeloperoxidase and is currently in clinical trials for the potential treatment of cardiovascular diseases. Concerns over idiosyncratic toxicity arising from bioactivation of the thiouracil motif to reactive species in the liver have been largely mitigated through the physicochemical (molecular weight, lipophilicity, and topological polar surface area) characteristics of PF-06282999, which generally favor elimination via nonmetabolic routes. To test this hypothesis, pharmacokinetics and disposition studies were initiated with PF-06282999 using animals and in vitro assays, with the ultimate goal of predicting human pharmacokinetics and elimination mechanisms. Consistent with its physicochemical properties, PF-06282999 was resistant to metabolic turnover from liver microsomes and hepatocytes from animals and humans and was devoid of cytochrome P450 inhibition. In vitro transport studies suggested moderate intestinal permeability and minimal transporter-mediated hepatobiliary disposition. PF-06282999 demonstrated moderate plasma protein binding across all of the species. Pharmacokinetics in preclinical species characterized by low to moderate plasma clearances, good oral bioavailability at 3- to 5-mg/kg doses, and renal clearance as the projected major clearance mechanism in humans. Human pharmacokinetic predictions using single-species scaling of dog and/or monkey pharmacokinetics were consistent with the parameters observed in the first-in-human study, conducted in healthy volunteers at a dose range of 20-200 mg PF-06282999. In summary, disposition characteristics of PF-06282999 were relatively similar across preclinical species and humans, with renal excretion of the unchanged parent emerging as the principal clearance mechanism in humans, which was anticipated based on its physicochemical properties and

  1. An inactivated influenza D virus vaccine partially protects cattle from respiratory disease caused by homologous challenge.

    PubMed

    Hause, Ben M; Huntimer, Lucas; Falkenberg, Shollie; Henningson, Jamie; Lechtenberg, Kelly; Halbur, Tom

    2017-02-01

    Originally isolated from swine, the proposed influenza D virus has since been shown to be common in cattle. Inoculation of IDV to naïve calves resulted in mild respiratory disease histologically characterized by tracheitis. As several studies have associated the presence of IDV with acute bovine respiratory disease (BRD), we sought to investigate the efficacy of an inactivated IDV vaccine. Vaccinated calves seroconverted with hemagglutination inhibition titers 137-169 following two doses. Non-vaccinated calves challenged with a homologous virus exhibited signs of mild respiratory disease from days four to ten post challenge which was significantly different than negative controls at days five and nine post challenge. Peak viral shedding of approximately 5 TCID50/mL was measured in nasal and tracheal swabs and bronchoalveolar lavage fluids four to six days post challenge. Viral titers were significantly (P<0.05) decreased 1.4 TCID50/mL, 3.6 TCID50/mL and 5.0 TCID50/mL, respectively, in the aforementioned samples collected from vaccinated animals compared to non-vaccinated controls at peak shedding. Viral antigen was detected in the respiratory epithelium of the nasal turbinates and trachea by immunohistochemistry from all unvaccinated calves but in significantly fewer vaccinates. Inflammation characterized by neutrophils was observed in the nasal turbinate and trachea but not appreciably in lungs. Together these results support an etiologic role for IDV in BRD and demonstrate that partial protection is afforded by an inactivated vaccine.

  2. Partial X chromosome trisomy with functional disomy of Xp due to failure of X inactivation

    SciTech Connect

    Gustashaw, K.M.; Zurcher, V.; Dickerman, L.H.; Stallard, R.; Willard, H.F.

    1994-10-15

    A 5-month-old girl with mild phenotypic abnormalities, developmental delay, and seizures was found to have the de novo karyotype 46,XX,-13,+der(13)t(X;13)(p21.2;p11.1). The partial trisomy of Xp21.2 {yields} pter was confirmed with fluorescence in situ hybridization, using an X chromosome painting probe and several cosmid and YAC probes for Xp sequences. Replication banding showed that one of the structurally normal X chromosomes was late-replicating, but that the Xp segment of the der(13) was early-replicating in all cells examined. Since segments of the X chromosome separated from the X inactivation center in Xq13.2 cannot undergo X inactivation, the result is functional disomy of distal Xp. As the loss of short arm material from chromosome 13 is not considered to be clinically significant, the genomic imbalance of Xp expressed in this patient most likely accounts for her abnormal phenotype. 39 refs., 5 figs., 1 tab.

  3. Partially irreversible paresis of the deep peroneal nerve caused by osteocartilaginous exostosis of the fibula without affecting the tibialis anterior muscle.

    PubMed

    Paprottka, Felix Julian; Machens, Hans-Günther; Lohmeyer, Jörn Andreas

    2012-08-01

    Dysfunction of the lower limb's muscles can cause severe impairment and immobilisation of the patient. As one of the leg's major motor and sensory nerves, the deep peroneal nerve (synonym: deep fibular nerve) plays a very important role in muscle innervation in the lower extremities. We report the case of a 19-year-old female patient, who suffered from a brace-like exostosis 6-cm underneath her left fibular head causing a partially irreversible paresis of her deep peroneal nerve. This nerve damage resulted in complete atrophy of her extensor digitorum longus and extensor hallucis longus muscle, and in painful sensory disturbance at her left shin and first web space. The tibialis anterior muscle stayed intact because its motor branch left the deep peroneal nerve proximal to the nerve lesion. Diagnosis was first verified 6 years after the onset of symptoms by a magnetic resonance imaging (MRI) scan of her complete left lower leg. Subsequently, the patient was operated on in our clinic, where a neurolysis was performed and the 4-cm-long osteocartilaginous exostosis was removed. Paralysis was already irreversible but sensibility returned completely after neurolysis. The presented case shows that an osteocartilaginous exostosis can be the cause for partial deep peroneal nerve paresis. If this disorder is diagnosed at an early stage, nerve damage is reversible. Typical for an exostosis is its first appearance during the juvenile growth phase.

  4. Irreversible Electroporation

    PubMed Central

    Narayanan, Govindarajan

    2015-01-01

    Irreversible electroporation (IRE) is a predominantly nonthermal ablative technology that uses high-voltage, low-energy DC current pulses to induce cell death. Thermal ablative technologies such as radiofrequency ablation, microwave ablation, and cryoablation have several applications in oncology but have limitations that have been established. IRE has shown promise to overcome some of these limitations. This article reviews the basics of the technology, patient selection, clinical applications, practical pointers, and the published data. PMID:26622097

  5. X inactivation in Rett syndrome: A preliminary study showing partial preferential inactivation of paternal X with the M27{beta} probe

    SciTech Connect

    Camus, P.; Abbadi, N.; Gilgenkrantz, S.

    1994-04-15

    Rett syndrome (RS) is a severe progressive neurological disorder occurring exclusively in females. Most cases are sporadic. The few familial cases (less than 1%) cannot be explained by a simple mode of inheritance. Several hypotheses have been proposed: X-linked male lethal mutation, maternal uniparental disomy, fresh mutation on the X chromosome, involvement of mitochondrial DNA and differential inactivation with metabolic interference of X-borne alleles. The authors have examined the pattern of X inactivation in 10 affected girls who were selected according to the clinical criteria previously described and accepted by the French Rett Scientific Committee. The X inactivation pattern was studied by analysis of methylation at the hypervariable locus DXS255 with the M27{beta} probe. The results show a more-or-less skewed inactivation of paternal X in 8 Rett females, and 2 cases of symmetrical inactivation. In control girls, inactivation was symmetrical cases and the maternal X has been preferentially inactivated in the other 2 cases. In no case was a total skewed inactivation observed. Though there was clear evidence for a preferential paternal X inactivation that was statistically significant further studies are necessary to establish a relationship between X inactivation pattern and Rett syndrome.

  6. Irreversible cycle in linear irreversible thermodynamics

    NASA Astrophysics Data System (ADS)

    Wang, Xian-Zhi

    2010-10-01

    The reversible Carnot cycle in reversible thermodynamics is composed of two reversible heat exchange processes and two reversible adiabatic processes. We construct an irreversible cycle in linear irreversible thermodynamics by analogy with the reversible Carnot cycle. The irreversible cycle is composed of two linear irreversible heat exchange processes and two linear irreversible adiabatic processes. It is found that the Curzon-Alhborn efficiency can be attained if the power for each of the four linear irreversible processes reaches its maximum. The maximum efficiency is the Carnot efficiency. The strong coupling condition is prerequisite for the respective attainment of the Curzon-Alhborn efficiency and the Carnot efficiency.

  7. Specific labeling and partial inactivation of cytochrome oxidase by fluorescein mercuric acetate.

    PubMed

    Stonehuerner, J; O'Brien, P; Kendrick, L; Hall, J; Millett, F

    1985-09-25

    Addition of 1 eq of fluorescein mercuric acetate (FMA) to beef heart cytochrome oxidase was found to inhibit the steady-state electron transfer activity by 50%, but further additions up to 10 eq had no additional effect on activity. The partial inhibition caused by FMA is thus similar to that observed with other mercury compounds (Mann, A. J., and Auer, H. E. (1980) J. Biol. Chem. 255, 454-458). The fluorescence of FMA was quenched by a factor of 10 upon binding to cytochrome oxidase, consistent with the involvement of a sulfhydryl group. However, addition of mercuric chloride to FMA-cytochrome oxidase resulted in an increase in fluorescence, suggesting that FMA was displaced from the high affinity binding site. Cytochrome c binding to FMA-cytochrome oxidase resulted in a 10% decrease in the fluorescence, possibly caused by Forster energy transfer from FMA to the cytochrome c heme. The binding site for FMA in cytochrome oxidase was investigated by carrying out sodium dodecyl sulfate gel electrophoresis under progressively milder dissociation conditions. When FMA-cytochrome oxidase was dissociated with 3% sodium dodecyl sulfate and 6 M urea, FMA was predominantly bound to subunit II following electrophoresis. However, when the dissociation was carried out at 4 degrees C in the absence of urea with progressively smaller amounts of lithium dodecyl sulfate, the labeling of subunit II decreased and that of subunit I increased. These experiments demonstrate that mercury compounds bind to a high affinity site on cytochrome oxidase, possibly located in subunit I, but then migrate to subunit II under the normal sodium dodecyl sulfate gel electrophoresis conditions. A definitive assignment of the high affinity binding site in the native enzyme cannot be made, however, because it is possible that mercury compounds can migrate from one sulfhydryl to another under even the mildest electrophoresis conditions.

  8. Differences in dopamine receptor reserve for N-n-propylnorapomorphine enantiomers: single unit recording studies after partial inactivation of receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline.

    PubMed

    Cox, R F; Waszczak, B L

    1989-01-01

    Previous studies with (S)-(+)-N-n-propylnorapomorphine (NPA), an enantiomer of the potent dopaminergic agonist (R)-(-)-NPA, showed that this compound had a complex pharmacological profile. For example, (S)-(+)NPA had weak dopaminergic agonist potency, in that it could slow and ultimately stop firing of substantia nigra and ventral tegmental area dopamine neurons. However, antagonist properties were also evident inasmuch as immediate pretreatment with a low dose of (S)-(+)-NPA caused a significant rightward shift of the (R)-(-)-NPA dose-response curve. This dual agonist-antagonist nature of (S)-(+)-NPA suggested a low intrinsic efficacy for (S)-(+)-NPA. To test this hypothesis, we conducted dose-response studies for the inhibition of rat substantia nigra dopamine cell firing by (R)-(-)- and (S)-(+)-NPA 1 day after partial irreversible dopamine receptor inactivation with 6 mg/kg N-ethoxycarbonyl-2-ethoxy-1-2-dihydroquinoline (EEDQ) in an ethanol vehicle. This degree of inactivation resulted in a significant, parallel, rightward shift of the (R)-(-)-NPA dose-response curve relative to ethanol-treated control rats, with no loss of maximal response. After pretreatment with the same dose of EEDQ, however, the maximal response to (S)-(+)-NPA was reduced by 22% with no shift on the dose axis. The dose-response curves for control and EEDQ-treated groups were subjected to Furchgott analysis to determine per cent response versus fractional occupancy relationships for each drug. A steep hyperbolic relationship was revealed for (R)-(-)-NPA. Fifty per cent and maximal (greater than 95%) inhibitions of cell firing occurred at 3.5% and approximately 32% receptor occupancies, respectively. Hence, for (R)-(-)-NPA there is about a 68% receptor reserve in this model. The same analysis for (S)-(+)-NPA yielded an occupancy versus response plot that was more shallow and linear. Half-maximal effects occurred at 66% occupancy and the maximal response (96% inhibition) required 94% occupancy

  9. The inactivation of the sortilin gene leads to a partial disruption of prosaposin trafficking to the lysosomes

    SciTech Connect

    Zeng, Jibin; Racicott, Jesse; Morales, Carlos R.

    2009-11-01

    Lysosomes are intracellular organelles which contain enzymes and activator proteins involved in the digestion and recycling of a variety of cellular and extracellular substances. We have identified a novel sorting receptor, sortilin, which is involved in the lysosomal trafficking of the sphingolipid activator proteins, prosaposin and GM{sub 2}AP, and the soluble hydrolases cathepsin D, cathepsin H, and acid sphingomyelinase. Sortilin belongs to a growing family of receptors with homology to the yeast Vps10 protein, which acts as a lysosomal sorting receptor for carboxypeptidase Y. In this study we examined the effects of the sortilin gene inactivation in mice. The inactivation of this gene did not yield any noticeable lysosomal pathology. To determine the existence of an alternative receptor complementing the sorting function of sortilin, we quantified the concentration of prosaposin in the lysosomes of the nonciliated epithelial cells lining the efferent ducts. These cells were chosen because they express sortilin and have a large number of lysosomes containing prosaposin. In addition, the nonciliated cells are known to endocytose luminal prosaposin that is synthesized and secreted by Sertoli cells into the seminiferous luminal fluids. Consequently, the nonciliated cells are capable of targeting both exogenous and endogenous prosaposin to the lysosomes. Using electron microscope immunogold labeling and quantitative analysis, our results demonstrate that inactivation of the sortilin gene produces a significant decrease of prosaposin in the lysosomes. When luminal prosaposin was excluded from the efferent ducts, the level of prosaposin in lysosomes was even lower in the mutant mice. Nonetheless, a significant amount of prosaposin continues to reach the lysosomal compartment. These results strongly suggest the existence of an alternative receptor that complements the function of sortilin and explains the lack of lysosomal storage disorders in the sortilin

  10. Potentiality, irreversibility, and death.

    PubMed

    Lizza, John P

    2005-02-01

    There has been growing concern about whether individuals who satisfy neurological criteria for death or who become non-heart-beating organ donors are really dead. This concern has focused on the issue of the potential for recovery that these individuals may still have and whether their conditions are irreversible. In this article I examine the concepts of potentiality and irreversibility that have been invoked in the discussions of the definition of death and non-heart-beating organ donation. I initially focus on the recent challenge by D. Alan Shewmon to accepting any neurological criterion of death. I argue that Shewmon relies on a problematic and unrealistic concept of potentiality, and that a better, more realistic concept of potentiality is consistent with accepting a neurological criterion for death. I then turn to an analysis of how the concept of irreversibility has been used in discussion of non-heart-beating organ donation. Similarly, I argue that some participants in this discussion have invoked a problematic and unrealistic concept of irreversibility. I then propose an alternative, more realistic account of irreversibility that explains how "irreversibility" should be understood in the definition and criteria of death.

  11. Structural Analysis of Mammalian Cytochrome P450 2B4 Covalently Bound to the Mechanism-Based Inactivator tert-Butylphenylacetylene: Insight into Partial Enzymatic Activity†‡

    PubMed Central

    Gay, Sean C.; Zhang, Haoming; Wilderman, P. Ross; Roberts, Arthur G.; Liu, Tong; Li, Sheng; Lin, Hsia-lien; Zhang, Qinghai; Woods, Virgil L.; Stout, C. David; Hollenberg, Paul F.; Halpert, James R.

    2011-01-01

    A combined structural and computational analysis of rabbit cytochrome P450 2B4 covalently bound to the mechanism-based inactivator tert-butylphenylacetylene (tBPA) has yielded insight into how the enzyme retains partial activity. Since conjugation to tBPA modifies a highly conserved active site residue, the residual activity of tBPA-labeled 2B4 observed in previous studies was puzzling. Here we describe the first crystal structures of a modified mammalian P450, which show an oxygenated metabolite of tBPA conjugated to Thr 302 of helix I. These results are consistent with previous studies that identified Thr 302 as the site of conjugation. In each structure, the core of 2B4 remains unchanged, but the arrangement of plastic regions differs. This results in one structure that is compact and closed. In this conformation, tBPA points toward helix B′, making a 31° angle with the heme plane. This conformation is in agreement with previously performed in silico experiments. However, dimerization of 2B4 in the other structure, which is caused by movement of the B/C loop and helices F through G, alters the position of tBPA. In this case, tBPA lies almost parallel to the heme plane due to the presence of helix F′ of the opposite monomer entering the active site to stabilize the dimer. However, docking experiments using this open form show that tBPA is able to rotate upward to give testosterone and 7-ethoxy-4-trifluoromethylcoumarin access to the heme, which could explain the previously observed partial activity. PMID:21510666

  12. Irreversibility time scale.

    PubMed

    Gallavotti, G

    2006-06-01

    Entropy creation rate is introduced for a system interacting with thermostats (i.e., for a system subject to internal conservative forces interacting with "external" thermostats via conservative forces) and a fluctuation theorem for it is proved. As an application, a time scale is introduced, to be interpreted as the time over which irreversibility becomes manifest in a process leading from an initial to a final stationary state of a mechanical system in a general nonequilibrium context. The time scale is evaluated in a few examples, including the classical Joule-Thompson process (gas expansion in a vacuum).

  13. Human 5-HT7 receptor-induced inactivation of forskolin-stimulated adenylate cyclase by risperidone, 9-OH-risperidone and other "inactivating antagonists".

    PubMed

    Toohey, Nicole; Klein, Michael T; Knight, Jessica; Smith, Carol; Teitler, Milt

    2009-09-01

    We have previously reported on the unusual human 5-hydroxytryptamine(7) (h5-HT(7)) receptor-inactivating properties of risperidone, 9-OH-risperidone, bromocriptine, methiothepin, metergoline, and lisuride. Inactivation was defined as the inability of 10 microM 5-HT to stimulate cAMP accumulation after brief exposure and thorough removal of the drugs from HEK293 cells expressing h5-HT(7) receptors. Herein we report that brief exposure of the h5-HT(7) receptor-expressing cells to inactivating drugs, followed by removal of the drugs, results in potent and efficacious irreversible inhibition of forskolin-stimulated adenylate cyclase activity. Pretreatment, followed by removal of the inactivating drugs inhibited 10 microM forskolin-stimulated adenylate cyclase activity with potencies similar to the drugs' affinities for the h5-HT(7) receptor. The actions of the inactivating drugs were pertussis toxin-insensitive, indicating the lack of G(i) in their mechanism(s) of action. Methiothepin and bromocriptine maximally inhibited 10 microM forskolin-stimulated adenylate cyclase, whereas the other drugs produced partial inhibition, indicating the drugs are inducing slightly different inactive conformations of the h5-HT(7) receptor. Maximal effects of these inactivating drugs occurred within 15 to 30 min of exposure of the cells to the drugs. A G(s)-mediated inhibition of forskolin-stimulated activity has never been reported. The inactivating antagonists seem to induce a stable conformation of the h5-HT(7) receptor, which induces an altered state of G(s), which, in turn, inhibits forskolin-mediated stimulation of adenylate cyclase. These and previous observations indicate that the inactivating antagonists represent a unique class of drugs and may reveal GPCR regulatory mechanisms previously unknown. These drugs may produce innovative approaches to the development of therapeutic drugs.

  14. Partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza A/H1N1 2009: case-control study in Mexico City

    PubMed Central

    Garcia-Garcia, Lourdes; Valdespino-Gómez, Jose Luis; Lazcano-Ponce, Eduardo; Jimenez-Corona, Aida; Higuera-Iglesias, Anjarath; Cruz-Hervert, Pablo; Cano-Arellano, Bulmaro; Garcia-Anaya, Antonio; Ferreira-Guerrero, Elizabeth; Baez-Saldaña, Renata; Ferreyra-Reyes, Leticia; Ponce-de-León-Rosales, Samuel; Alpuche-Aranda, Celia; Rodriguez-López, Mario Henry; Perez-Padilla, Rogelio; Hernandez-Avila, Mauricio

    2009-01-01

    Objective To evaluate the association of 2008-9 seasonal trivalent inactivated vaccine with cases of influenza A/H1N1 during the epidemic in Mexico. Design Frequency matched case-control study. Setting Specialty hospital in Mexico City, March to May 2009. Participants 60 patients with laboratory confirmed influenza A/H1N1 and 180 controls with other diseases (not influenza-like illness or pneumonia) living in Mexico City or the State of Mexico and matched for age and socioeconomic status. Main outcome measures Odds ratio and effectiveness of trivalent inactivated vaccine against influenza A/H1N1. Results Cases were more likely than controls to be admitted to hospital, undergo invasive mechanical ventilation, and die. Controls were more likely than cases to have chronic conditions that conferred a higher risk of influenza related complications. In the multivariate model, influenza A/H1N1 was independently associated with trivalent inactivated vaccine (odds ratio 0.27, 95% confidence interval 0.11 to 0.66) and underlying conditions (0.15, 0.08 to 0.30). Vaccine effectiveness was 73% (95% confidence interval 34% to 89%). None of the eight vaccinated cases died. Conclusions Preliminary evidence suggests some protection from the 2008-9 trivalent inactivated vaccine against pandemic influenza A/H1N1 2009, particularly severe forms of the disease, diagnosed in a specialty hospital during the influenza epidemic in Mexico City. PMID:19808768

  15. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  16. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-12-25

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat. 11 figs.

  17. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, John C.; Swift, Gregory W.; Migliori, Albert

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. the second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  18. Chemical studies on the inactivation of Escherichia coli RTEM beta-lactamase by clavulanic acid.

    PubMed

    Charnas, R L; Fisher, J; Knowles, J R

    1978-05-30

    Incubation of clavulanic acid with the beta-lactamase from Escherichia coli RTEM leads to enzyme-catalyzed depletion of clavulanic acid, to transient inhibition, and to irreversible inactivation of the enzyme. Both the transiently inhibited and the irreversibly inactivated species show a marked increase in the absorbance at 281 nm that is proportional to the decrease in enzyme activity. Hydroxylamine treatment of irreversibly inactivated enzyme restores about one-third of the catalytic activity, with a concomitant decrease in absorbance at 281 nm. Polyacrylamide isoelectric focusing of the irreversibly inactivated enzyme shows three bands of approximately equal intensity, different from native enzyme. Upon hydroxylamine treatment, one of the three bands disappears and now focuses identically with native enzyme. It is evident that the irreversible inactivation of enzyme by an excess of clavulanic acid generates three products, one of which can be reactivated by hydroxylamine.

  19. Origin of irreversibility of cell cycle start in budding yeast.

    PubMed

    Charvin, Gilles; Oikonomou, Catherine; Siggia, Eric D; Cross, Frederick R

    2010-01-19

    Budding yeast cells irreversibly commit to a new division cycle at a regulatory transition called Start. This essential decision-making step involves the activation of the SBF/MBF transcription factors. SBF/MBF promote expression of the G1 cyclins encoded by CLN1 and CLN2. Cln1,2 can activate their own expression by inactivating the Whi5 repressor of SBF/MBF. The resulting transcriptional positive feedback provides an appealing, but as yet unproven, candidate for generating irreversibility of Start. Here, we investigate the logic of the Start regulatory module by quantitative single-cell time-lapse microscopy, using strains in which expression of key regulators is efficiently controlled by changes of inducers in a microfluidic chamber. We show that Start activation is ultrasensitive to G1 cyclin. In the absence of CLN1,2-dependent positive feedback, we observe that Start transit is reversible, due to reactivation of the Whi5 transcriptional repressor. Introduction of the positive feedback loop makes Whi5 inactivation and Start activation irreversible, which therefore guarantees unidirectional entry into S phase. A simple mathematical model to describe G1 cyclin turn on at Start, entirely constrained by empirically measured parameters, shows that the experimentally measured ultrasensitivity and transcriptional positive feedback are necessary and sufficient dynamical characteristics to make the Start transition a bistable and irreversible switch. Our study thus demonstrates that Start irreversibility is a property that arises from the architecture of the system (Whi5/SBF/Cln2 loop), rather than the consequence of the regulation of a single component (e.g., irreversible protein degradation).

  20. Selective inactivation of parvulin-like peptidyl-prolyl cis/trans isomerases by juglone.

    PubMed

    Hennig, L; Christner, C; Kipping, M; Schelbert, B; Rücknagel, K P; Grabley, S; Küllertz, G; Fischer, G

    1998-04-28

    In contrast to FK506 binding proteins and cyclophilins, the parvulin family of peptidyl-prolyl cis/trans isomerases (PPIases; E.C. 5.2.1.8) cannot be inhibited by either FK506 or cyclosporin A. We have found that juglone, 5-hydroxy-1,4-naphthoquinone, irreversibly inhibits the enzymatic activity of several parvulins, like the E. coli parvulin, the yeast Ess1/Ptf1, and human Pin1, in a specific manner, thus allowing selective inactivation of these enzymes in the presence of other PPIases. The mode of action was studied by analyzing the inactivation kinetics and the nature of products of the reaction of E. coli parvulin and its Cys69Ala variant with juglone. For all parvulins investigated, complete inactivation was obtained by a slow process that is characterized by pseudo-first-order rate constants in the range of 5.3 x 10(-)4 to 4. 5 x 10(-)3 s-1. The inactivated parvulin contains two juglone molecules that are covalently bound to the side chains of Cys41 and Cys69 because of a Michael addition of the thiol groups to juglone. Redox reactions did not contribute to the inactivation process. Because thiol group modification was shown to proceed 5-fold faster than the rate of enzyme inactivation, it was considered as a necessary but not sufficient condition for inactivation. When measured by far-UV circular dichroism (CD), the rate of structural alterations following thiol group modification parallels exactly the rate of inactivation. Thus, partial unfolding of the active site of the parvulins was thought to be the cause of the deterioration of PPIase activity.

  1. Cell wall as a target for bacteria inactivation by pulsed electric fields

    PubMed Central

    Pillet, Flavien; Formosa-Dague, Cécile; Baaziz, Houda; Dague, Etienne; Rols, Marie-Pierre

    2016-01-01

    The integrity and morphology of bacteria is sustained by the cell wall, the target of the main microbial inactivation processes. One promising approach to inactivation is based on the use of pulsed electric fields (PEF). The current dogma is that irreversible cell membrane electro-permeabilisation causes the death of the bacteria. However, the actual effect on the cell-wall architecture has been poorly explored. Here we combine atomic force microscopy and electron microscopy to study the cell-wall organization of living Bacillus pumilus bacteria at the nanoscale. For vegetative bacteria, exposure to PEF led to structural disorganization correlated with morphological and mechanical alterations of the cell wall. For spores, PEF exposure led to the partial destruction of coat protein nanostructures, associated with internal alterations of cortex and core. Our findings reveal for the first time that the cell wall and coat architecture are directly involved in the electro-eradication of bacteria. PMID:26830154

  2. Cyanide inactivation of hydrogenase from Azotobacter vinelandii

    SciTech Connect

    Seefeldt, L.C.; Arp, D.J. )

    1989-06-01

    The effects of cyanide on membrane-associated and purified hydrogenase from Azotobacter vinelandii were characterized. Inactivation of hydrogenase by cyanide was dependent on the activity (oxidation) state of the enzyme. Active (reduced) hydrogenase showed no inactivation when treated with cyanide over several hours. Treatment of reversibly inactive (oxidized) states of both membrane-associated and purified hydrogenase, however, resulted in a time-dependent, irreversible loss of hydrogenase activity. The rate of cyanide inactivation was dependent on the cyanide concentration and was an apparent first-order process for purified enzyme (bimolecular rate constant, 23.1 M{sup {minus}1} min{sup {minus}1} for CN{sup {minus}}). The rate of inactivation decreased with decreasing pH. ({sup 14}C)cyanide remained associated with cyanide-inactivated hydrogenase after gel filtration chromatography, with a stoichiometry of 1.7 mol of cyanide bound per mol of inactive enzyme. The presence of saturating concentrations of CO had no effect on the rate or extent of cyanide inactivation of hydrogenases. The results indicate that cyanide can cause a time-dependent, irreversible inactivation of hydrogenase in the oxidized, activatable state but has no effect when hydrogenase is in the reduced, active state.

  3. Cyanide inactivation of hydrogenase from Azotobacter vinelandii.

    PubMed Central

    Seefeldt, L C; Arp, D J

    1989-01-01

    The effects of cyanide on membrane-associated and purified hydrogenase from Azotobacter vinelandii were characterized. Inactivation of hydrogenase by cyanide was dependent on the activity (oxidation) state of the enzyme. Active (reduced) hydrogenase showed no inactivation when treated with cyanide over several hours. Treatment of reversibly inactive (oxidized) states of both membrane-associated and purified hydrogenase, however, resulted in a time-dependent, irreversible loss of hydrogenase activity. The rate of cyanide inactivation was dependent on the cyanide concentration and was an apparent first-order process for purified enzyme (bimolecular rate constant, 23.1 M-1 min-1 for CN-). The rate of inactivation decreased with decreasing pH. [14C]cyanide remained associated with cyanide-inactivated hydrogenase after gel filtration chromatography, with a stoichiometry of 1.7 mol of cyanide bound per mol of inactive enzyme. The presence of saturating concentrations of CO had no effect on the rate or extent of cyanide inactivation of hydrogenases. The results indicate that cyanide can cause a time-dependent, irreversible inactivation of hydrogenase in the oxidized, activatable state but has no effect when hydrogenase is in the reduced, active state. PMID:2656648

  4. Irreversible thermal denaturation of Torpedo californica acetylcholinesterase.

    PubMed Central

    Kreimer, D. I.; Shnyrov, V. L.; Villar, E.; Silman, I.; Weiner, L.

    1995-01-01

    Thermal denaturation of Torpedo californica acetylcholinesterase, a disulfide-linked homodimer with 537 amino acids in each subunit, was studied by differential scanning calorimetry. It displays a single calorimetric peak that is completely irreversible, the shape and temperature maximum depending on the scan rate. Thus, thermal denaturation of acetylcholinesterase is an irreversible process, under kinetic control, which is described well by the two-state kinetic scheme N-->D, with activation energy 131 +/- 8 kcal/mol. Analysis of the kinetics of denaturation in the thermal transition temperature range, by monitoring loss of enzymic activity, yields activation energy of 121 +/- 20 kcal/mol, similar to the value obtained by differential scanning calorimetry. Thermally denatured acetylcholinesterase displays spectroscopic characteristics typical of a molten globule state, similar to those of partially unfolded enzyme obtained by modification with thiol-specific reagents. Evidence is presented that the partially unfolded states produced by the two different treatments are thermodynamically favored relative to the native state. PMID:8563632

  5. Kinetic studies on the inactivation of Escherichia coli RTEM beta-lactamase by clavulanic acid.

    PubMed

    Fisher, J; Charnas, R L; Knowles, J R

    1978-05-30

    The kinetic details of the irreversible inactivation of the Escherichia coli RTEM beta-lactamase by clavulanic acid have been elucidated. Clavulanate is destroyed by the enzyme and simultaneously inhibits it by producing two catalytically inactive forms. One of these is transiently stable and decomposes to free enzyme (k = 3.8 X 10(-3) S-1), while the other corresponds to an irreversibly inactivated form. The transient complex is formed from the Michaelis complex at a rate (k approximately 3 X 10(-2) S-1) which is some threefold faster than the rate of formation of the irreversibly inactivated complex. The transient complex is, therefore, the principle enzyme form present after short time periods. In the presence of excess clavulanate, however, all the enzyme accumulates into the irreversibly inactivated form. The number of clavulanate turnovers that occur prior to complete enzyme inactivation is 115.

  6. Drought stress and carbon assimilation in a warming climate: Reversible and irreversible impacts.

    PubMed

    Feller, Urs

    2016-09-20

    Global change is characterized by increased CO2 concentration in the atmosphere, increasing average temperature and more frequent extreme events including drought periods, heat waves and flooding. Especially the impacts of drought and of elevated temperature on carbon assimilation are considered in this review. Effects of extreme events on the subcellular level as well as on the whole plant level may be reversible, partially reversible or irreversible. The photosynthetically active biomass depends on the number and the size of mature leaves and the photosynthetic activity in this biomass during stress and subsequent recovery phases. The total area of active leaves is determined by leaf expansion and senescence, while net photosynthesis per leaf area is primarily influenced by stomatal opening (stomatal conductance), mesophyll conductance, activity of the photosynthetic apparatus (light absorption and electron transport, activity of the Calvin cycle) and CO2 release by decarboxylation reactions (photorespiration, dark respiration). Water status, stomatal opening and leaf temperature represent a "magic triangle" of three strongly interacting parameters. The response of stomata to altered environmental conditions is important for stomatal limitations. Rubisco protein is quite thermotolerant, but the enzyme becomes at elevated temperature more rapidly inactivated (decarbamylation, reversible effect) and must be reactivated by Rubisco activase (carbamylation of a lysine residue). Rubisco activase is present under two forms (encoded by separate genes or products of alternative splicing of the pre-mRNA from one gene) and is very thermosensitive. Rubisco activase was identified as a key protein for photosynthesis at elevated temperature (non-stomatal limitation). During a moderate heat stress Rubisco activase is reversibly inactivated, but during a more severe stress (higher temperature and/or longer exposure) the protein is irreversibly inactivated, insolubilized and

  7. Tumor Ablation with Irreversible Electroporation

    PubMed Central

    Al-Sakere, Bassim; André, Franck; Bernat, Claire; Connault, Elisabeth; Opolon, Paule; Davalos, Rafael V.; Rubinsky, Boris; Mir, Lluis M.

    2007-01-01

    We report the first successful use of irreversible electroporation for the minimally invasive treatment of aggressive cutaneous tumors implanted in mice. Irreversible electroporation is a newly developed non-thermal tissue ablation technique in which certain short duration electrical fields are used to permanently permeabilize the cell membrane, presumably through the formation of nanoscale defects in the cell membrane. Mathematical models of the electrical and thermal fields that develop during the application of the pulses were used to design an efficient treatment protocol with minimal heating of the tissue. Tumor regression was confirmed by histological studies which also revealed that it occurred as a direct result of irreversible cell membrane permeabilization. Parametric studies show that the successful outcome of the procedure is related to the applied electric field strength, the total pulse duration as well as the temporal mode of delivery of the pulses. Our best results were obtained using plate electrodes to deliver across the tumor 80 pulses of 100 µs at 0.3 Hz with an electrical field magnitude of 2500 V/cm. These conditions induced complete regression in 12 out of 13 treated tumors, (92%), in the absence of tissue heating. Irreversible electroporation is thus a new effective modality for non-thermal tumor ablation. PMID:17989772

  8. Comments to Irreversibility in Thermodynamics

    NASA Technical Reports Server (NTRS)

    Zak, M.

    1995-01-01

    The problem of irreversibility in thermodynamics was revisited and analyzed on the microscopic, stochastic, and macroscopic levels of description. It was demonstrated that Newtonian dynamics can be represented in the Reynolds form, a new phenomenological force with non-Lipschitz properties was introduced, and additional non- Lipschitz thermodynamical forces were incorporated into macroscopic models of transport phenomena.

  9. Benzene-Induced Uncoupling of Naphthalene Dioxygenase Activity and Enzyme Inactivation by Production of Hydrogen Peroxide

    PubMed Central

    Lee, Kyoung

    1999-01-01

    Naphthalene dioxygenase (NDO) is a multicomponent enzyme system that oxidizes naphthalene to (+)-cis-(1R,2S)-1,2-dihydroxy-1,2-dihydronaphthalene with consumption of O2 and two electrons from NAD(P)H. In the presence of benzene, NADH oxidation and O2 utilization were partially uncoupled from substrate oxidation. Approximately 40 to 50% of the consumed O2 was detected as hydrogen peroxide. The rate of benzene-dependent O2 consumption decreased with time, but it was partially increased by the addition of catalase in the course of the O2 consumption by NDO. Detailed experiments showed that the total amount of O2 consumed and the rate of benzene-induced O2 consumption increased in the presence of hydrogen peroxide-scavenging agents, and further addition of the terminal oxygenase component (ISPNAP) of NDO. Kinetic studies showed that ISPNAP was irreversibly inactivated in the reaction that contained benzene, but the inactivation was relieved to a high degree in the presence of catalase and partially relieved in the presence of 0.1 mM ferrous ion. Benzene- and naphthalene-reacted ISPNAP gave almost identical visible absorption spectra. In addition, hydrogen peroxide added at a range of 0.1 to 0.6 mM to the reaction mixtures inactivated the reduced ISPNAP containing mononuclear iron. These results show that hydrogen peroxide released during the uncoupling reaction acts both as an inhibitor of benzene-dependent O2 consumption and as an inactivator of ISPNAP. It is proposed that the irreversible inactivation of ISPNAP occurs by a Fenton-type reaction which forms a strong oxidizing agent, hydroxyl radicals (·OH), from the reaction of hydrogen peroxide with ferrous mononuclear iron at the active site. Furthermore, when [14C]benzene was used as the substrate, cis-benzene 1,2-dihydrodiol formed by NDO was detected. This result shows that NDO also couples a trace amount of benzene to both O2 consumption and NADH oxidation. PMID:10217759

  10. Ecological optimization for generalized irreversible Carnot refrigerators

    NASA Astrophysics Data System (ADS)

    Chen, Lingen; Xiaoqin, Zhu; Sun, Fengrui; Wu, Chih

    2005-01-01

    The optimal ecological performance of a Newton's law generalized irreversible Carnot refrigerator with the losses of heat resistance, heat leakage and internal irreversibility is derived by taking an ecological optimization criterion as the objective, which consists of maximizing a function representing the best compromise between the exergy output rate and exergy loss rate (entropy production rate) of the refrigerator. Numerical examples are given to show the effects of heat leakage and internal irreversibility on the optimal performance of generalized irreversible refrigerators.

  11. Irreversible evolution of quantum chaos

    NASA Astrophysics Data System (ADS)

    Ugulava, A.; Chotorlishvili, L.; Nickoladze, K.

    2005-05-01

    The pendulum is the simplest system having all the basic properties inherent in dynamic stochastic systems. In the present paper we investigate the pendulum with the aim to reveal the properties of a quantum analogue of dynamic stochasticity or, in other words, to obtain the basic properties of quantum chaos. It is shown that a periodic perturbation of the quantum pendulum (similarly to the classical one) in the neighborhood of the separatrix can bring about irreversible phenomena. As a result of recurrent passages between degenerate states, the system gets self-chaotized and passes from the pure state to the mixed one. Chaotization involves the states, the branch points of whose levels participate in a slow “drift” of the system along the Mathieu characteristics this “drift” being caused by a slowly changing variable field. Recurrent relations are obtained for populations of levels participating in the irreversible evolution process. It is shown that the entropy of the system first grows and, after reaching the equilibrium state, acquires a constant value.

  12. Irreversible inhibition of delta 5-3-oxosteroid isomerase by 2-substituted progesterones.

    PubMed Central

    Penning, T M

    1985-01-01

    2 alpha-Cyanoprogesterone (I) and 2-hydroxymethyleneprogesterone (II) were synthesized and screened as irreversible active-site-directed inhibitors of the delta 5-3-oxosteroid isomerase (EC 5.3.3.1) from Pseudomonas testosteroni. Both compounds were found to inhibit the purified bacterial enzyme in a time-dependent manner. In either case the inactivated enzyme could be dialysed without return of activity, indicating that a stable covalent bond had formed between the inhibitor and the enzyme. Inactivation mediated by compounds (I) and (II) followed pseudo-first-order kinetics, and at higher inhibitor concentrations saturation was observed. The competitive inhibitor 17 beta-oestradiol offered protection against the inactivation mediated by both compounds, and initial-rate studies indicated that compounds (I) and (II) can also act as competitive inhibitors yielding Ki values identical with those generated during inactivation experiments. 2 alpha-Cyanoprogesterone (I) and 2-hydroxymethyleneprogesterone (II) thus appear to be active-site-directed. To compare the reactivity of these 2-substituted progesterones with other irreversible inhibitors of the isomerase, 3 beta-spiro-oxiranyl-5 alpha-pregnan-20 beta-ol (III) was synthesized as the C21 analogue of 3 beta-spiro-oxiranyl-5 alpha-androstan-17 beta-ol, which is a potent inactivator of the isomerase [Pollack, Kayser & Bevins (1979) Biochem. Biophys. Res. Commun. 91, 783-790]. Comparison of the bimolecular rate constants for inactivation (k+3/Ki) mediated by compounds (I)-(III) indicated the following order of reactivity: (III) greater than (II) greater than (I). 2-Mercaptoethanol offers complete protection against the inactivation of the isomerase mediated by 2 alpha-cyanoprogesterone (I). Under the conditions of inactivation compound (I) appears to be completely stable, and no evidence could be obtained for enolate ion formation in the presence or absence of enzyme. It is suggested that cyanoprogesterone inactivates

  13. Beta-lactamase inactivation by mechanism-based reagents.

    PubMed

    Fisher, J; Belasco, J G; Charnas, R L; Khosla, S; Knowles, J R

    1980-05-16

    The mechanistic pathway followed by the E. coli RTEM beta-lactamase has been studied with a view to clarifying the mode of action of a number of recently discovered inactivators of the enzyme. There is clear evidence that the beta-lactamase-catalysed hydrolysis of the 7-alpha-methoxycephem, cefoxitin, proceeds via an acyl-enzyme intermediate. An analysis of the inactivation reactions of all the known beta-lactam derivatives that result in irreversible loss of enzyme activity permits the identification of three structural features required for a beta-lactamase inactivator. The application of these principles suggests a new group of mechanism-based inactivators of the enzyme: the sulphones of N-acyl derivatives of 6-beta-aminopenicillanic acid that are themselves poor substrates for the enzyme. These sulphones are powerful inactivators of the beta-lactamase.

  14. Trypsin inactivation by intact Hymenolepis diminuta (Cestoda): some characteristics of the inactivated enzyme.

    PubMed

    Schroeder, L L; Pappas, P W; Means, G E

    1981-06-01

    In the presence of intact Hymenolepis diminuta, trypsin was inactivated; intact worms had no apparent effect on subtilisin, pepsin, or papain. Inactivation of trypsin was demonstrable using azoalbumin as a substrate, but the inactivated enzyme retained full catalytic activity against benzoyl-DL-arginine-p-nitroanilide, p-tosyl-L-arginine methyl ester (low molecular weight synthetic trypsin substrates) and p-nitro-p-guanidinobenzoate (an active site titrant). Inactivation was not reversible under conditions of heating, freezing and thawing, or prolonged dialysis of the enzyme. Analyses of inactivated 3H-trypsin by cationic and SDS-polyacrylamide gel electrophoresis, and gel chromatography failed to indicate the presence of a high molecular weight trypsin inhibitor associated with the inactivated enzyme; no low molecular weight, dissociable inhibitor was demonstrable following thermal denaturation of the inactivated enzyme. Analyses of trypsin after incubation in the presence of pulse-labeled worms also failed to demonstrate the presence of any inhibitor of worm origin associated with the inactivated enzyme. The data suggest that inactivation is the result of a small structural or conformational change in the enzyme molecule, a change which partially (rather than totally) inactivates the enzyme towards protein substrates.

  15. Inactivation of Caliciviruses

    PubMed Central

    Nims, Raymond; Plavsic, Mark

    2013-01-01

    The Caliciviridae family of viruses contains clinically important human and animal pathogens, as well as vesivirus 2117, a known contaminant of biopharmaceutical manufacturing processes employing Chinese hamster cells. An extensive literature exists for inactivation of various animal caliciviruses, especially feline calicivirus and murine norovirus. The caliciviruses are susceptible to wet heat inactivation at temperatures in excess of 60 °C with contact times of 30 min or greater, to UV-C inactivation at fluence ≥30 mJ/cm2, to high pressure processing >200 MPa for >5 min at 4 °C, and to certain photodynamic inactivation approaches. The enteric caliciviruses (e.g.; noroviruses) display resistance to inactivation by low pH, while the non-enteric species (e.g.; feline calicivirus) are much more susceptible. The caliciviruses are inactivated by a variety of chemicals, including alcohols, oxidizing agents, aldehydes, and β-propiolactone. As with inactivation of viruses in general, inactivation of caliciviruses by the various approaches may be matrix-, temperature-, and/or contact time-dependent. The susceptibilities of the caliciviruses to the various physical and chemical inactivation approaches are generally similar to those displayed by other small, non-enveloped viruses, with the exception that the parvoviruses and circoviruses may require higher temperatures for inactivation, while these families appear to be more susceptible to UV-C inactivation than are the caliciviruses. PMID:24276023

  16. Blueberry polyphenol oxidase: Characterization and the kinetics of thermal and high pressure activation and inactivation.

    PubMed

    Terefe, Netsanet Shiferaw; Delon, Antoine; Buckow, Roman; Versteeg, Cornelis

    2015-12-01

    Partially purified blueberry polyphenol oxidase (PPO) in Mcllvaine buffer (pH=3.6, typical pH of blueberry juice) was subjected to processing at isothermal-isobaric conditions at temperatures from 30 to 80 °C and pressure from 0.1 to 700 MPa. High pressure processing at 30-50 °C at all pressures studied caused irreversible PPO activity increase with a maximum of 6.1 fold increase at 500 MPa and 30 °C. Treatments at mild pressure-mild temperature conditions (0.1-400 MPa, 60 °C) also caused up to 3 fold PPO activity increase. Initial activity increase followed by a decrease occurred at relatively high pressure-mild temperature (400-600 MPa, 60 °C) and mild pressure-high temperature (0.1-400 MPa, 70-80 °C) combinations. At temperatures higher than 76 °C, monotonic decrease in PPO activity occurred at 0.1 MPa and pressures higher than 500 MPa. The activation/inactivation kinetics of the enzyme was successfully modelled assuming consecutive reactions in series with activation followed by inactivation.

  17. Photosensitized oxidation and inactivation of pyocyanin, a virulence factor of Pseudomonas aeruginosa.

    PubMed

    Reszka, Krzysztof J; Denning, Gerene M; Britigan, Bradley E

    2006-01-01

    Pyocyanin (PyO-) (1-hydroxy-5-methylphenazine) is a cytotoxic compound secreted by Pseudomonas aeruginosa, an omnipresent bacterium and a human pathogen. We report that visible light illumination in the presence of rose bengal, or riboflavin, in aerated solutions (pH 7.0-7.2) induces irreversible loss of the pigment's characteristic absorption band at 690 nm, indicating its oxidation. This photobleaching was paralleled by generation of a multiline Electron Paramagnetic Resonance (EPR) spectrum attributed to a PyO(-)-derived radical. The reaction was dependent on the presence of air, sensitizers and light, was inhibited by sodium azide and was unaffected by ethanol. This suggests that PyO- was oxidized largely via singlet oxygen and that hydroxyl radicals were not involved. The photochemically modified pigment was less efficient in oxidizing NAD(P)H and generated less superoxide (by approximately 50%) than the intact PyO-, indicating its partial inactivation. 1-Methoxy-5-methylphenazine, a PyO- analog in which the -O- moiety was replaced by the methoxy group (-OMe), was resistant to oxidation, suggesting that oxidation of PyO- involves its phenolate moiety. These results also suggest that photosensitization could be a potentially useful method for inactivation of PyO- and, possibly, detoxification of superficial wounds (skin, eye) infected with P. aeruginosa.

  18. N-Alkoxyheterocycles As Irreversible Photooxidants†

    PubMed Central

    Wosinska, Zofia M.; Stump, Faye L.; Ranjan, Rajeev; Lorance, Edward D.; Finley, GeNita N.; Patel, Priya P.; Khawaja, Muzamil A.; Odom, Katie L.; Kramer, Wolfgang H.; Gould, Ian R.

    2015-01-01

    Irreversible photooxidation based on N–O bond fragmentation is demonstrated for N-methoxyheterocycles in both the singlet and triplet excited state manifolds. The energetic requirements for bond fragmentation are studied in detail. Bond fragmentation in the excited singlet manifold is possible for ππ* singlet states with energies significantly larger than the N–O bond dissociation energy of ca 55 kcal mol−1. For the nπ* triplet states, N–O bond fragmentation does not occur in the excited state for orbital overlap and energetic reasons. Irreversible photooxidation occurs in the singlet states by bond fragmentation followed by electron transfer. Irreversible photooxidation occurs in the triplet states via bimolecular electron transfer to the donor followed by bond fragmentation. Using these two sensitization schemes, donors can be irreversibly oxidized with oxidation potentials ranging from ca 1.6–2.2 V vs SCE. The corresponding N-ethylheterocycles are characterized as conventional reversible photooxidants in their triplet states. The utility of these sensitizers is demonstrated by irreversibly generating the guanosine radical cation in buffered aqueous solution. PMID:24354634

  19. A Case of SSRI Induced Irreversible Parkinsonism

    PubMed Central

    Khan, Shahbaj A; Azad, Sudip

    2015-01-01

    Serotonin specific reuptake inhibitors (SSRI) are widely used antidepressants for variety of clinical conditions and have found popularity. They are sometimes associated with extrapyramidal side effects including Parkinsonism. We report a case of generalized anxiety disorder on treatment with SSRI (fluoxetine / sertraline) who developed irreversible Parkinsonism. SSRI are known to cause reversible or irreversible motor disturbances through pathophysiological changes in basal ganglion motor system by altering the dopamine receptors postsynaptically. Clinician should keep risk benefit ratio in mind and change of antidepressant of different class may be considered. Case is reported to alert physicians to possibility of motor system damage while treating with SSRI. PMID:25859504

  20. Efficiency of Rectification: Reversible vs. Irreversible Regimes

    NASA Astrophysics Data System (ADS)

    Sokolov, I. M.

    2002-11-01

    Both man-made locomotive devices and molecular motors use gears to transform a reciprocating motion into a directed one. One of the most common gears is a rectifier, a mechanically irreversible appliance. The maximal energetic efficiency of an isothermic gear is bounded by unity, as a consequence of the Second Law. However, approaching this ideal efficiency does not imply approaching reversibility. We discuss what properties of a rectifier mostly influence the transduction efficiency and show that an appliance which locks under backward force is just the one which can approach the ideal efficiency either in the reversible or in the irreversible regime.

  1. Pilot Decision-Making in Irreversible Emergencies

    ERIC Educational Resources Information Center

    Winter, Scott R.

    2013-01-01

    The purpose of this study was to determine if a reflexive learning treatment utilizing select case studies could enhance the decision-making of pilots who encounter an irreversible emergency. Participants, who consisted of members of the subject university's professional pilot program, were divided into either a control or experimental group and…

  2. Absorption media for irreversibly gettering thionyl chloride

    DOEpatents

    Buffleben, George; Goods, Steven H.; Shepodd, Timothy; Wheeler, David R.; Whinnery, Jr., LeRoy

    2002-01-01

    Thionyl chloride is a hazardous and reactive chemical used as the liquid cathode in commercial primary batteries. Contrary to previous thinking, ASZM-TEDA.RTM. carbon (Calgon Corporation) reversibly absorbs thionyl chloride. Thus, several candidate materials were examined as irreversible getters for thionyl chloride. The capacity, rate and effect of temperature were also explored. A wide variety of likely materials were investigated through screening experiments focusing on the degree of heat generated by the reaction as well as the material absorption capacity and irreversibility, in order to help narrow the group of possible getter choices. More thorough, quantitative measurements were performed on promising materials. The best performing getter was a mixture of ZnO and ASZM-TEDA.RTM. carbon. In this example, the ZnO reacts with thionyl chloride to form ZnCl.sub.2 and SO.sub.2. The SO.sub.2 is then irreversibly gettered by ASZM-TEDA.RTM. carbon. This combination of ZnO and carbon has a high capacity, is irreversible and functions effectively above -20.degree. C.

  3. Markov Chain Monte Carlo and Irreversibility

    NASA Astrophysics Data System (ADS)

    Ottobre, Michela

    2016-06-01

    Markov Chain Monte Carlo (MCMC) methods are statistical methods designed to sample from a given measure π by constructing a Markov chain that has π as invariant measure and that converges to π. Most MCMC algorithms make use of chains that satisfy the detailed balance condition with respect to π; such chains are therefore reversible. On the other hand, recent work [18, 21, 28, 29] has stressed several advantages of using irreversible processes for sampling. Roughly speaking, irreversible diffusions converge to equilibrium faster (and lead to smaller asymptotic variance as well). In this paper we discuss some of the recent progress in the study of nonreversible MCMC methods. In particular: i) we explain some of the difficulties that arise in the analysis of nonreversible processes and we discuss some analytical methods to approach the study of continuous-time irreversible diffusions; ii) most of the rigorous results on irreversible diffusions are available for continuous-time processes; however, for computational purposes one needs to discretize such dynamics. It is well known that the resulting discretized chain will not, in general, retain all the good properties of the process that it is obtained from. In particular, if we want to preserve the invariance of the target measure, the chain might no longer be reversible. Therefore iii) we conclude by presenting an MCMC algorithm, the SOL-HMC algorithm [23], which results from a nonreversible discretization of a nonreversible dynamics.

  4. A new microscopic level of irreversibility

    SciTech Connect

    Prigogine, I.

    1987-01-01

    In this paper, the non-exponential decay is analyzed with the help of simple computer experiments performed by T. Petrosky, simulating classical radiation damping. The non-exponential decay is studied and shown to depend on the preparation of the system. However, whatever the initial preparation, the system reaches the decay predicted by classical radiation theory after a short time we call the Zeno's time. The similitude of Petrosky's results with computer experiments for the approach to equilibrium in many-body systems is emphasized. However, while there one deals with times which are multiple of the relaxation time, the irreversibility manifest in radiation theory occurs always over a much shorter time scale, the Zeno's time. In atomic systems, this would be a time order of 10/sup /minus/18/ seconds. These results are of great interest for the understanding of the microscopic mechanism of radiation. Let us consider a charged oscillator. In a first stage, this oscillator has to produce the field oscillators to which it may transfer energy through the usual resonance mechanism. Radiation appears therefore as a kind of non linear autocatalytic process, involving a self-organization mechanism. The behavior during the Zeno period can be explained easily in terms of subdynamics as introduced by the Brussel's group. We see that there is no transition from reversibility to irreversibility. Irreversible processes start at the very moment at which the system is prepared. It is important to stress that an unstable particle is itself the result of irreversible processes. As a result, an unstable particle (or an excited atomic state) can no more be described in terms of wave functions, as irreversible processes are not included in Schroedinger's equation. 14 refs., 3 figs.

  5. Metabolically Labile Fumarate Esters Impart Kinetic Selectivity to Irreversible Inhibitors.

    PubMed

    Zaro, Balyn W; Whitby, Landon R; Lum, Kenneth M; Cravatt, Benjamin F

    2016-12-14

    Electrophilic small molecules are an important class of chemical probes and drugs that produce biological effects by irreversibly modifying proteins. Examples of electrophilic drugs include covalent kinase inhibitors that are used to treat cancer and the multiple sclerosis drug dimethyl fumarate. Optimized covalent drugs typically inactivate their protein targets rapidly in cells, but ensuing time-dependent, off-target protein modification can erode selectivity and diminish the utility of reactive small molecules as chemical probes and therapeutics. Here, we describe an approach to confer kinetic selectivity to electrophilic drugs. We show that an analogue of the covalent Bruton's tyrosine kinase (BTK) inhibitor Ibrutinib bearing a fumarate ester electrophile is vulnerable to enzymatic metabolism on a time-scale that preserves rapid and sustained BTK inhibition, while thwarting more slowly accumulating off-target reactivity in cell and animal models. These findings demonstrate that metabolically labile electrophilic groups can endow covalent drugs with kinetic selectivity to enable perturbation of proteins and biochemical pathways with greater precision.

  6. Irreversible inhibition of human cathepsins B, L, S and K by hypervalent tellurium compounds.

    PubMed

    Cunha, Rodrigo L O R; Gouvêa, Iuri E; Feitosa, Geovana P V; Alves, Márcio F M; Brömme, Dieter; Comasseto, João V; Tersariol, Ivarne L S; Juliano, Luiz

    2009-11-01

    The inhibition of human cysteine cathepsins B, L, S and K was evaluated by a set of hypervalent tellurium compounds (telluranes) comprising both organic and inorganic derivatives. All telluranes studied showed a time- and concentration-dependent irreversible inhibition of the cathepsins, and their second-order inactivation rate constants were determined. The organic derivatives were potent inhibitors of the cathepsins and clear specificities were detected, which were parallel to their known substrate specificities. In all cases, the activity of the tellurane-inhibited cathepsins was recovered by treatment of the inactivated enzymes with reducing agents. The maximum stoichiometry of the reaction between cysteine residues and telluranes were also determined. The presented data indicate that it is possible to design organic compounds with a tellurium(IV) moiety as a novel warhead that covalently modifies the catalytic cysteine, and which also form strong interactions with subsites of cathepsins B, L, S and K, resulting in more specific inhibition.

  7. Maximum power, ecological function and efficiency of an irreversible Carnot cycle: a cost and effectiveness optimization

    NASA Astrophysics Data System (ADS)

    Aragón-González, G.; Canales-Palma, A.; León-Galicia, A.; Morales-Gómez, J. R.

    2008-12-01

    In this work we include, for the Carnot cycle, irreversibilities of linear finite rate of heat transferences between the heat engine and its reservoirs, heat leak between the reservoirs and internal dissipations of the working fluid. A first optimization of the power output, the efficiency and ecological function of an irreversible Carnot cycle, with respect to: internal temperature ratio, time ratio for the heat exchange and the allocation ratio of the heat exchangers; is performed. For the second and third optimizations, the optimum values for the time ratio and internal temperature ratio are substituted into the equation of power and, then, the optimizations with respect to the cost and effectiveness ratio of the heat exchangers are performed. Finally, a criterion of partial optimization for the class of irreversible Carnot engines is herein presented.

  8. Substituted isatoic anhydrides: selective inactivators of trypsin-like serine proteases.

    PubMed

    Gelb, M H; Abeles, R H

    1986-04-01

    Derivatives of isatoic anhydride were prepared and tested as inhibitors of serine proteases. A number of isatoic anhydrides with positively charged substituents irreversibly inactivated several trypsin-like enzymes and preferentially inactivated trypsin over chymotrypsin. Further selectivity was obtained by introduction of an aromatic group on the N-1 position of isatoic anhydride. 7-(Aminomethyl)-1-benzylisatoic anhydride was prepared and was a selective inactivator of thrombin; thus it is possible to prepare derivatives of isatoic anhydride that are highly enzyme selective without attaching peptide recognition structures.

  9. Irreversible enzyme inhibition kinetics and drug-drug interactions.

    PubMed

    Mohutsky, Michael; Hall, Stephen D

    2014-01-01

    This chapter describes the types of irreversible inhibition of drug-metabolizing enzymes and the methods commonly employed to quantify the irreversible inhibition and subsequently predict the extent and time course of clinically important drug-drug interactions.

  10. Multiscale multifractal time irreversibility analysis of stock markets

    NASA Astrophysics Data System (ADS)

    Jiang, Chenguang; Shang, Pengjian; Shi, Wenbin

    2016-11-01

    Time irreversibility is one of the most important properties of nonstationary time series. Complex time series often demonstrate even multiscale time irreversibility, such that not only the original but also coarse-grained time series are asymmetric over a wide range of scales. We study the multiscale time irreversibility of time series. In this paper, we develop a method called multiscale multifractal time irreversibility analysis (MMRA), which allows us to extend the description of time irreversibility to include the dependence on the segment size and statistical moments. We test the effectiveness of MMRA in detecting multifractality and time irreversibility of time series generated from delayed Henon map and binomial multifractal model. Then we employ our method to the time irreversibility analysis of stock markets in different regions. We find that the emerging market has higher multifractality degree and time irreversibility compared with developed markets. In this sense, the MMRA method may provide new angles in assessing the evolution stage of stock markets.

  11. Meiotic sex chromosome inactivation.

    PubMed

    Turner, James M A

    2007-05-01

    X chromosome inactivation is most commonly studied in the context of female mammalian development, where it performs an essential role in dosage compensation. However, another form of X-inactivation takes place in the male, during spermatogenesis, as germ cells enter meiosis. This second form of X-inactivation, called meiotic sex chromosome inactivation (MSCI) has emerged as a novel paradigm for studying the epigenetic regulation of gene expression. New studies have revealed that MSCI is a special example of a more general mechanism called meiotic silencing of unsynapsed chromatin (MSUC), which silences chromosomes that fail to pair with their homologous partners and, in doing so, may protect against aneuploidy in subsequent generations. Furthermore, failure in MSCI is emerging as an important etiological factor in meiotic sterility.

  12. Irreversible photoinhibition of photosystem II is caused by exposure of Synechocystis cells to strong light for a prolonged period.

    PubMed

    Allakhverdiev, Suleyman I; Tsvetkova, Nelly; Mohanty, Prasanna; Szalontai, Balász; Moon, Byoung Yong; Debreczeny, Mónika; Murata, Norio

    2005-07-15

    Irreversible photoinhibition of photosystem II (PSII) occurred when Synechocystis sp. PCC 6803 cells were exposed to very strong light for a prolonged period. When wild-type cells were illuminated at 20 degrees C for 2 h with light at an intensity of 2,500 micromol photons m(-2) s(-1), the oxygen-evolving activity of PSII was almost entirely and irreversibly lost, whereas the photochemical reaction center in PSII was inactivated only reversibly. The extent of irreversible photoinhibition was enhanced at lower temperatures and by the genetically engineered rigidification of membrane lipids. Western and Northern blotting demonstrated that, after cells had undergone irreversible photoinhibition, the precursor to D1 protein in PSII was synthesized but not processed properly. These observations may suggest that exposure of Synechocystis cells to strong light results in the irreversible photoinhibition of the oxygen-evolving activity of PSII via impairment of the processing of pre-D1 and that this effect of strong light is enhanced by the rigidification of membrane lipids.

  13. Inactivated pepsin inhibits neutrophil activation by Fcgamma-receptor-dependent and independent stimuli.

    PubMed

    Kustiawan, Iwan; Derksen, Ninotska; Rispens, Theo

    2016-08-01

    Pepsin is widely used to produce F(ab')2 fragments of immunoglobulin G (IgG). In many cases, at least part of the pepsin will remain present in the F(ab')2 preparation, albeit in (irreversibly) inactivated form. Here we report on a potent immunomodulatory effect of irreversibly inactivated pepsin on activated human neutrophils. Degranulation, induced by coated IgG or via cytochalasin B/N-formyl-Met-Leu-Phe, was measured by quantifying elastase release, and was found to be inhibited in a dose-dependent manner by inactivated pepsin. Since a number of intravenous immunoglobulin (IVIg) products are also treated by limited digestion with pepsin, we investigated if pepsin would be present in quantities large enough to inhibit neutrophil activation. The amounts of pepsin detected in three different pepsin-treated IVIg products were found to be too low to induce an effect, at least in an in vitro setting.

  14. The connection between logical and thermodynamic irreversibility

    NASA Astrophysics Data System (ADS)

    Ladyman, James; Presnell, Stuart; Short, Anthony J.; Groisman, Berry

    There has recently been a good deal of controversy about Landauer's Principle, which is often stated as follows: the erasure of one bit of information in a computational device is necessarily accompanied by a generation of kT ln 2 heat. This is often generalised to the claim that any logically irreversible operation cannot be implemented in a thermodynamically reversible way. Norton [2005. Eaters of the lotus: Landauer's principle and the return of Maxwell's demon. Studies in History and Philosophy of Modern Physics, 36, 375-411] and Maroney [2005. The (absence of a) relationship between thermodynamic and logical reversibility. Studies in History and Philosophy of Modern Physics, 36, 355-374] both argue that Landauer's Principle has not been shown to hold in general, and Maroney offers a method that he claims instantiates the operation Reset in a thermodynamically reversible way. In this paper we defend the qualitative form of Landauer's Principle, and clarify its quantitative consequences (assuming the second law of thermodynamics). We analyse in detail what it means for a physical system to implement a logical transformation L, and we make this precise by defining the notion of an L-machine. Then we show that logical irreversibility of L implies thermodynamic irreversibility of every corresponding L-machine. We do this in two ways. First, by assuming the phenomenological validity of the Kelvin statement of the second law, and second, by using information-theoretic reasoning. We illustrate our results with the example of the logical transformation 'Reset', and thereby recover the quantitative form of Landauer's Principle.

  15. Irreversible translation arrest in the reperfused brain

    PubMed Central

    DeGracia, Donald J; Hu, Bingren R

    2012-01-01

    Irreversible translation arrest occurs in reperfused neurons that will die by delayed neuronal death. It is now recognized that suppression of protein synthesis is a general response of eukaryotic cells to exogenous stressors. Indeed, stress-induced translation arrest can be viewed as a component of cell stress responses, and consists of initiation, maintenance, and termination phases that work in concert with stress-induced transcriptional mechanisms. Within this framework, we review translation arrest in reperfused neurons. This framework provides a basis to recognize that phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is the initiator of translation arrest, and a key marker indicating activation of neuronal stress responses. However, eIF2 alpha phosphorylation is reversible. Other phases of stress-induced translation arrest appear to contribute to irreversible translation arrest specifically in ischemic vulnerable neuron populations. We detail two lines of evidence supporting this view. First, ischemia, as a stress stimulus, induces irreversible co-translational protein misfolding and aggregation after 4 to 6 h of reperfusion, trapping protein synthesis machinery into functionally inactive protein aggregates. Second, ischemia and reperfusion leads to modifications of stress granules (SGs) that sequester functionally inactive 48S preinitiation complexes to maintain translation arrest. At later reperfusion durations, these mechanisms may converge such that SGs become sequestered in protein aggregates. These mechanisms result in elimination of functionally active ribosomes and preclude recovery of protein synthesis in selectively vulnerable neurons. Thus, recognizing translation arrest as a component of endogenous cellular stress response pathways will aid in making sense of the complexities of postischemic translation arrest. PMID:16926841

  16. Chaos and irreversibility in simple model systems.

    PubMed

    Hoover, Wm. G.; Posch, Harald A.

    1998-06-01

    The multifractal link between chaotic time-reversible mechanics and thermodynamic irreversibility is illustrated for three simple chaotic model systems: the Baker Map, the Galton Board, and many-body color conductivity. By scaling time, or the momenta, or the driving forces, it can be shown that the dissipative nature of the three thermostated model systems has analogs in conservative Hamiltonian and Lagrangian mechanics. Links between the microscopic nonequilibrium Lyapunov spectra and macroscopic thermodynamic dissipation are also pointed out. (c) 1998 American Institute of Physics.

  17. Ascorbate-induced oxidative inactivation of Zn2+-glycerophosphocholine cholinephosphodiesterase.

    PubMed

    Sok, D E

    1998-03-01

    Zn2+-glycerophosphocholine cholinephosphodiesterase, responsible for the conversion of glycerophosphocholine into glycerol and phosphocholine, was inactivated during incubation with ascorbic acid at 38 degrees C. The inclusion of copper ions or Fe2+ accelerated the ascorbate-induced inactivation, with Cu2+ or Cu+ being much more effective than Fe2+, suggestive of ascorbate-mediated oxidation. Dehydroascorbic acid had no effect on the phosphodiesterase, but H2O2 inactivated the enzyme in a concentration-dependent manner. Also, the enzyme was inactivated partially by a superoxide anion-generating system but not an HOCl generator. In support of involvement of H2O2 in the ascorbate action, catalase and superoxide dismutase expressed a complete and a partial protection, respectively. However, hydroxy radical scavengers such as mannitol, benzoate, or dimethyl sulfoxide were incapable of preventing the ascorbate action, excluding the participation of extraneous .OH. Although p-nitrophenylphosphocholine exhibited a modest protection against the ascorbate action, a remarkable protection was expressed by amino acids, especially by histidine. In addition, imidazole, an electron donor, showed a partial protection. Separately, when Cu2+-induced inactivation of the phosphodiesterase was compared with the ascorbate-mediated one, the protection and pH studies indicate that the mechanism for the ascorbate action is different from that for the Cu2+ action. Here, it is proposed that Zn2+-glycerophosphocholine cholinephosphodiesterase is one of brain membrane proteins susceptible to oxidative inactivation.

  18. Kv4 channels exhibit modulation of closed-state inactivation in inside-out patches.

    PubMed Central

    Beck, E J; Covarrubias, M

    2001-01-01

    The mechanisms of inactivation gating of the neuronal somatodendritic A-type K(+) current and the cardiac I(to) were investigated in Xenopus oocyte macropatches expressing Kv4.1 and Kv4.3 channels. Upon membrane patch excision (inside-out), Kv4.1 channels undergo time-dependent acceleration of macroscopic inactivation accompanied by a parallel partial current rundown. These changes are readily reversible by patch cramming, suggesting the influence of modulatory cytoplasmic factors. The consequences of these perturbations were investigated in detail to gain insights into the biophysical basis and mechanisms of inactivation gating. Accelerated inactivation at positive voltages (0 to +110 mV) is mainly the result of reducing the time constant of slow inactivation and the relative weight of the slow component of inactivation. Concomitantly, the time constants of closed-state inactivation at negative membrane potentials (-90 to -50 mV) are substantially decreased in inside-out patches. Deactivation is moderately accelerated, and recovery from inactivation and the peak G--V curve exhibit little or no change. In agreement with more favorable closed-state inactivation in inside-out patches, the steady-state inactivation curve exhibits a hyperpolarizing shift of approximately 10 mV. Closed-state inactivation was similarly enhanced in Kv4.3. An allosteric model that assumes significant closed-state inactivation at all relevant voltages can explain Kv4 inactivation gating and the modulatory changes. PMID:11463631

  19. Structure of suicide-inactivated. beta. -hydroxydecanoyl-thioester dehydrase

    SciTech Connect

    Schwab, J.M.; Ho, C.K.; Li, W.B.; Townsend, C.A.; Salituro, G.M.

    1986-05-01

    ..beta..-Hydroxydecanoylthioester dehydrase, the key enzyme in biosynthesis of unsaturated fatty acids under anaerobic conditions, equilibrates thioesters of (R)-3-hydroxydecanoic acid, E-2-decenoic acid, and Z-3-decenoic acid. Dehydrase is irreversibly inactivated by the N-acetylcysteamine thioester of 3-decynoic acid (3-decynoyl-NAC), via dehydrase-catalyzed isomerization to 2,3-decadienoyl-NAC. To probe the relationship between normal catalysis and suicide inactivation, the structure of the inactivated enzyme has been studied. 3-(2-/sup 13/C)Decynoyl-NAC was synthesized and incubated with dehydrase. /sup 13/C NMR showed that attack of 2,3-decadienoyl-NAC by the active site histidine gives 3-histidinyl-3-decenoyl-NAC, which slowly rearranges to the more stable ..delta../sup 2/ isomer. Model histidine-allene adducts have been made and characterized. Analysis of NMR data show that the C=C configuration of the decenoyl moiety of enzyme-bound inactivator is E. The suggestion that the mechanism of dehydrase inactivation parallels its normal mechanism of action is supported these findings.

  20. Inactivation of Anopheles gambiae Glutathione Transferase ε2 by Epiphyllocoumarin

    PubMed Central

    Marimo, Patience; Hayeshi, Rose; Mukanganyama, Stanley

    2016-01-01

    Glutathione transferases (GSTs) are part of a major family of detoxifying enzymes that can catalyze the reductive dehydrochlorination of dichlorodiphenyltrichloroethane (DDT). The delta and epsilon classes of insect GSTs have been implicated in conferring resistance to this insecticide. In this study, the inactivation of Anopheles gambiae GSTε2 by epiphyllocoumarin (Tral 1) was investigated. Recombinant AgGSTε2 was expressed in Escherichia coli cells containing a pET3a-AGSTε2 plasmid and purified by affinity chromatography. Tral 1 was shown to inactivate GSTε2 both in a time-dependent manner and in a concentration-dependent manner. The half-life of GSTε2 in the presence of 25 μM ethacrynic acid (ETA) was 22 minutes and with Tral 1 was 30 minutes, indicating that Tral 1 was not as efficient as ETA as an inactivator. The inactivation parameters kinact and KI were found to be 0.020 ± 0.001 min−1 and 7.5 ± 2.1 μM, respectively, after 90 minutes of incubation. Inactivation of GSTε2 by Tral 1 implies that Tral 1 covalently binds to this enzyme in vitro and would be expected to exhibit time-dependent effects on the enzyme in vivo. Tral 1, therefore, would produce irreversible effects when used together with dichlorodiphenyltrichloroethane (DDT) in malaria control programmes where resistance is mediated by GSTs. PMID:26925266

  1. Magnetic Irreversibility in VO2/Ni Bilayers

    NASA Astrophysics Data System (ADS)

    de La Venta, Jose; Lauzier, Josh; Sutton, Logan

    The temperature dependence of the coercivity and magnetization of VO2/Ni bilayers was studied. VO2 exhibits a well-known Structural Phase Transition (SPT) at 330-340 K, from a low temperature monoclinic (M) to a high temperature rutile (R) structure. The SPT of VO2 induces an inverse magnetoelastic effect that strongly modifies the coercivity and magnetization of the Ni films. In addition, the growth conditions allow tuning of the magnetic properties. Ni films deposited on top of VO2 (M) show an irreversible change in the coercivity after the first cycle through the high temperature phase, with a corresponding change in the surface morphology of VO2. On the other hand, the Ni films grown on top of VO2 (R) do not show this irreversibility. These results indicate that properties of magnetic films are strongly affected by the strain induced by materials that undergo SPT and that it is possible to control the magnetic properties by tuning the growth conditions.

  2. Irreversible sediment formation in green tea infusions.

    PubMed

    Xu, Yong-Quan; Chen, Gen-Sheng; Wang, Qiu-Shuang; Yuan, Hai-Bo; Feng, Chun-Hong; Yin, Jun-Feng

    2012-03-01

    The formation of irreversible tea sediment (IRS) and its chemical components in green tea infusions were investigated. The results showed that the amounts of IRS in the green tea infusions from various tea cultivars ranged from 0.10 to 1.47 mg/mL. The amount of IRS was influenced remarkably by the chemical components in the green tea infusion. Principal component analysis and regression analysis indicated that gallated catechins, Mn, Ca, caffeine, Na, and (-)-gallocatechin gallate (GCG) were the principal components. IRS (mg/mL) = -4.226 + 0.275 gallated catechins + 79.551 Na + 7.321 Mn + 21.055 Ca + 0.513 caffeine - 0.129 GCG (R2 = 0.697). The contents of the main chemical components in the reversible tea sediment (RTS) and IRS were markedly different, especially the minerals. Large amount of minerals participated in the formation of irreversible green tea sediment. The amount of IRS increased with the extraction temperature.

  3. Probabilistic Gompertz model of irreversible growth.

    PubMed

    Bardos, D C

    2005-05-01

    Characterizing organism growth within populations requires the application of well-studied individual size-at-age models, such as the deterministic Gompertz model, to populations of individuals whose characteristics, corresponding to model parameters, may be highly variable. A natural approach is to assign probability distributions to one or more model parameters. In some contexts, size-at-age data may be absent due to difficulties in ageing individuals, but size-increment data may instead be available (e.g., from tag-recapture experiments). A preliminary transformation to a size-increment model is then required. Gompertz models developed along the above lines have recently been applied to strongly heterogeneous abalone tag-recapture data. Although useful in modelling the early growth stages, these models yield size-increment distributions that allow negative growth, which is inappropriate in the case of mollusc shells and other accumulated biological structures (e.g., vertebrae) where growth is irreversible. Here we develop probabilistic Gompertz models where this difficulty is resolved by conditioning parameter distributions on size, allowing application to irreversible growth data. In the case of abalone growth, introduction of a growth-limiting biological length scale is then shown to yield realistic length-increment distributions.

  4. Irreversibility-inversions in 2D turbulence

    NASA Astrophysics Data System (ADS)

    Bragg, Andrew; de Lillo, Filippo; Boffetta, Guido

    2016-11-01

    We consider a recent theoretical prediction that for inertial particles in 2D turbulence, the nature of the irreversibility of their pair dispersion inverts when the particle inertia exceeds a certain value. In particular, when the particle Stokes number, St , is below a certain value, the forward-in-time (FIT) dispersion should be faster than the backward-in-time (BIT) dispersion, but for St above this value, this should invert so that BIT becomes faster than FIT dispersion. This non-trivial behavior arises because of the competition between two physically distinct irreversibility mechanisms that operate in different regimes of St . In 3D turbulence, both mechanisms act to produce faster BIT than FIT dispersion, but in 2D, the two mechanisms have opposite effects because of the inverse energy cascade in the turbulent velocity field. We supplement the qualitative argument given by Bragg et al. by deriving quantitative predictions of this effect in the short-time dispersion limit. These predictions are then confirmed by results of inertial particle dispersion in a direct numerical simulation of 2D turbulence.

  5. Irreversible heavy chain transfer to chondroitin.

    PubMed

    Lauer, Mark E; Hascall, Vincent C; Green, Dixy E; DeAngelis, Paul L; Calabro, Anthony

    2014-10-17

    We have recently demonstrated that the transfer of heavy chains (HCs) from inter-α-inhibitor, via the enzyme TSG-6 (tumor necrosis factor-stimulated gene 6), to hyaluronan (HA) oligosaccharides is an irreversible event in which subsequent swapping of HCs between HA molecules does not occur. We now describe our results of HC transfer experiments to chondroitin sulfate A, chemically desulfated chondroitin, chemoenzymatically synthesized chondroitin, unsulfated heparosan, heparan sulfate, and alginate. Of these potential HC acceptors, only chemically desulfated chondroitin and chemoenzymatically synthesized chondroitin were HC acceptors. The kinetics of HC transfer to chondroitin was similar to HA. At earlier time points, HCs were more widely distributed among the different sizes of chondroitin chains. As time progressed, the HCs migrated to lower molecular weight chains of chondroitin. Our interpretation is that TSG-6 swaps the HCs from the larger, reversible sites on chondroitin chains, which function as HC acceptors, onto smaller chondroitin chains, which function as irreversible HC acceptors. HCs transferred to smaller chondroitin chains were unable to be swapped off the smaller chondroitin chains and transferred to HA. HCs transferred to high molecular weight HA were unable to be swapped onto chondroitin. We also present data that although chondroitin was a HC acceptor, HA was the preferred acceptor when chondroitin and HA were in the same reaction mixture.

  6. Irreversible electroporation: state of the art.

    PubMed

    Wagstaff, Peter Gk; Buijs, Mara; van den Bos, Willemien; de Bruin, Daniel M; Zondervan, Patricia J; de la Rosette, Jean Jmch; Laguna Pes, M Pilar

    2016-01-01

    The field of focal ablative therapy for the treatment of cancer is characterized by abundance of thermal ablative techniques that provide a minimally invasive treatment option in selected tumors. However, the unselective destruction inflicted by thermal ablation modalities can result in damage to vital structures in the vicinity of the tumor. Furthermore, the efficacy of thermal ablation intensity can be impaired due to thermal sink caused by large blood vessels in the proximity of the tumor. Irreversible electroporation (IRE) is a novel ablation modality based on the principle of electroporation or electropermeabilization, in which electric pulses are used to create nanoscale defects in the cell membrane. In theory, IRE has the potential of overcoming the aforementioned limitations of thermal ablation techniques. This review provides a description of the principle of IRE, combined with an overview of in vivo research performed to date in the liver, pancreas, kidney, and prostate.

  7. Model simplification and loss of irreversibility

    NASA Astrophysics Data System (ADS)

    Jia, Chen

    2016-05-01

    In this paper, we reveal a general relationship between model simplification and irreversibility based on the model of continuous-time Markov chains with time-scale separation. According to the topological structure of the fast process, we divide the states of the chain into the transient states and the recurrent states. We show that a two-time-scale chain can be simplified to a reduced chain in two different ways: removal of the transient states and aggregation of the recurrent states. Both the two operations will lead to a decrease in the entropy production rate and its adiabatic part and will keep its nonadiabatic part the same. This suggests that although model simplification can retain almost all the dynamic information of the chain, it will lose some thermodynamic information as a trade-off.

  8. Geroconversion: irreversible step to cellular senescence

    PubMed Central

    Blagosklonny, Mikhail V

    2014-01-01

    Cellular senescence happens in 2 steps: cell cycle arrest followed, or sometimes preceded, by gerogenic conversion (geroconversion). Geroconvesrion is a form of growth, a futile growth during cell cycle arrest. It converts reversible arrest to irreversible senescence. Geroconversion is driven by growth-promoting, mitogen-/nutrient-sensing pathways such as mTOR. Geroconversion leads to hyper-secretory, hypertrophic and pro-inflammatory cellular phenotypes, hyperfunctions and malfunctions. On organismal level, geroconversion leads to age-related diseases and death. Rapamycin, a gerosuppressant, extends life span in diverse species from yeast to mammals. Stress–and oncogene-induced accelerated senescence, replicative senescence in vitro and life-long cellular aging in vivo all can be described by 2-step model. PMID:25483060

  9. Exergetic sustainability evaluation of irreversible Carnot refrigerator

    NASA Astrophysics Data System (ADS)

    Açıkkalp, Emin

    2015-10-01

    Purpose of this paper is to assess irreversible refrigeration cycle by using exergetic sustainability index. In literature, there is no application of exergetic sustainability index for the refrigerators and, indeed, this index has not been derived for refrigerators. In this study, exergetic sustainability indicator is presented for the refrigeration cycle and its relationships with other thermodynamics parameters including COP, exergy efficiency, cooling load, exergy destruction, ecological function and work input are investigated. Calculations are conducted for endoreversible and reversible cycles and then results obtained from the ecological function are compared. It is found that exergy efficiency, exergetic sustainable index reduce 47.595% and 59.689% and rising at the COP is 99.888% is obtained for endoreversible cycle. Similarly, exergy efficiency and exergetic sustainability index reduce 90.163% and 93.711% and rising of the COP is equal to 99.362%.

  10. Irreversible electroporation: state of the art

    PubMed Central

    Wagstaff, Peter GK; Buijs, Mara; van den Bos, Willemien; de Bruin, Daniel M; Zondervan, Patricia J; de la Rosette, Jean JMCH; Laguna Pes, M Pilar

    2016-01-01

    The field of focal ablative therapy for the treatment of cancer is characterized by abundance of thermal ablative techniques that provide a minimally invasive treatment option in selected tumors. However, the unselective destruction inflicted by thermal ablation modalities can result in damage to vital structures in the vicinity of the tumor. Furthermore, the efficacy of thermal ablation intensity can be impaired due to thermal sink caused by large blood vessels in the proximity of the tumor. Irreversible electroporation (IRE) is a novel ablation modality based on the principle of electroporation or electropermeabilization, in which electric pulses are used to create nanoscale defects in the cell membrane. In theory, IRE has the potential of overcoming the aforementioned limitations of thermal ablation techniques. This review provides a description of the principle of IRE, combined with an overview of in vivo research performed to date in the liver, pancreas, kidney, and prostate. PMID:27217767

  11. Calcium-binding parameter of Bacillus amyloliquefaciens alpha-amylase determined by inactivation kinetics.

    PubMed Central

    Tanaka, Atsushi; Hoshino, Eiichi

    2002-01-01

    The irreversible thermal inactivation and the thermodynamics of calcium ion binding of Bacillus amyloliquefaciens alpha-amylase in the absence of substrates were studied. The enzyme inactivation on heating was apparently followed by first-order kinetics. The enzyme was stabilized with an increased concentration of calcium ion and thus the inactivation was highly dependent on the state of calcium binding. The activation parameter for the inactivation suggests an unfolding of the enzyme protein upon heating. Values of both the activation enthalpy and entropy were increased with a higher calcium ion concentration. An inactivation kinetic model is based on the assumption of a two-stage unfolding transition in which the bivalent ion dissociation occurs in the first step followed by the secondary structural unfolding. This simple kinetic model provides both a qualitative and quantitative interpretation of calcium ion binding to the enzyme and its effect on the inactivation properties. The specific approximations of the kinetic model were strictly followed in the analysis to calculate the apparent inactivation rate at each calcium ion concentration in terms of the calcium-binding parameters. The enthalpy and entropy changes for the calcium ion binding were calculated to be -149 kJ/mol and -360 J.mol(-1).K(-1) respectively and these values suggest a strong enthalpic affinity for the bivalent ion binding to the enzyme protein. The thermodynamical interpretation attempts to provide clear relations between the terms of an apparent inactivation rate and the calcium binding. PMID:12049626

  12. Monte Carlo simulations of the short time dynamics of a first-order irreversible phase transition

    NASA Astrophysics Data System (ADS)

    Albano, Ezequiel V.

    2001-09-01

    The ZGB model (Ziff-Gulari-Barshad, Phys. Rev. Lett. 56 (1986) 2553) for the catalytic oxidation of carbon monoxide has a single parameter given by the normalized partial pressure of CO molecules ( PCO). For PCO⩾ PCOCoex≃0.52583 the surface of the catalyst becomes irreversibly covered by CO molecules and the system cannot escape from this state. However, for PCO slightly below PCOCoex the system reaches an active stationary state. So, just at PCOCoex a sharp first-order irreversible phase transition is observed. It is shown that a study of the short time dynamics of the ZGB model allows to obtain a fairly accurate evaluation of the upper spinodal point given by PCOUsp≃0.52675(5). This figure is in excellent agreement with extensive simulations performed using the constant coverage ensemble.

  13. Mesoscopic systems: classical irreversibility and quantum coherence.

    PubMed

    Barbara, Bernard

    2012-09-28

    Mesoscopic physics is a sub-discipline of condensed-matter physics that focuses on the properties of solids in a size range intermediate between bulk matter and individual atoms. In particular, it is characteristic of a domain where a certain number of interacting objects can easily be tuned between classical and quantum regimes, thus enabling studies at the border of the two. In magnetism, such a tuning was first realized with large-spin magnetic molecules called single-molecule magnets (SMMs) with archetype Mn(12)-ac. In general, the mesoscopic scale can be relatively large (e.g. micrometre-sized superconducting circuits), but, in magnetism, it is much smaller and can reach the atomic scale with rare earth (RE) ions. In all cases, it is shown how quantum relaxation can drastically reduce classical irreversibility. Taking the example of mesoscopic spin systems, the origin of irreversibility is discussed on the basis of the Landau-Zener model. A classical counterpart of this model is described enabling, in particular, intuitive understanding of most aspects of quantum spin dynamics. The spin dynamics of mesoscopic spin systems (SMM or RE systems) becomes coherent if they are well isolated. The study of the damping of their Rabi oscillations gives access to most relevant decoherence mechanisms by different environmental baths, including the electromagnetic bath of microwave excitation. This type of decoherence, clearly seen with spin systems, is easily recovered in quantum simulations. It is also observed with other types of qubits such as a single spin in a quantum dot or a superconducting loop, despite the presence of other competitive decoherence mechanisms. As in the molecular magnet V(15), the leading decoherence terms of superconducting qubits seem to be associated with a non-Markovian channel in which short-living entanglements with distributions of two-level systems (nuclear spins, impurity spins and/or charges) leading to 1/f noise induce τ(1)-like

  14. Enterovirus inactivation in soil.

    PubMed Central

    Yeager, J G; O'Brien, R T

    1979-01-01

    The inactivation of radioactively labeled poliovirus type 1 and coxsackievirus B 1 in soils saturated with surface water, groundwater, and septic tank liquor was directly proportional to temperature. Virus persistence was also related to soil type and the liquid amendment in which viruses were suspended. At 37 degrees C, no infectivity was recovered from saturated soil after 12 days; at 4 degrees C, viruses persisted for at least 180 days. No infectivity was recovered from dried soil regardless of temperature, soil type, or liquid amendment. Additional experiments showed that evaporation of soil water was largely responsible for the decreased recovery of infectivity from drying soil. Increased rates of virus inactivation at low soil moisture levels were also demonstrated. PMID:44178

  15. Hydrazine inactivates bacillus spores

    NASA Technical Reports Server (NTRS)

    Schubert, Wayne; Plett, G. A.; Yavrouian, A. H.; Barengoltz, J.

    2005-01-01

    Planetary Protection places requirements on the maximum number of viable bacterial spores that may be delivered by a spacecraft to another solar system body. Therefore, for such space missions, the spores that may be found in hydrazine are of concern. A proposed change in processing procedures that eliminated a 0.2 um filtration step propmpted this study to ensure microbial contamination issue existed, especially since no information was found in the literature to substantiate bacterial spore inactivation by hydrazine.

  16. Thermal Inactivation of Viruses

    DTIC Science & Technology

    1977-10-01

    Hammon. 1966. Studies on Japanese B encephalitis virus vaccines from tissue culture. VI. Development of a hamster kidney tissue culture inactivated... tissue culture passage, storage, temperature and drying on viability of SE polyoma virus. Exper. Biol. and Hed. Proc. of the Soc. for Exper. Biol...studies of heated tissue suspensions containing foot- and-mouth disease virus. Amer. J. Vet. Res. 20:510-521. Dupre’, M. V., and M. Frobisher. 1966

  17. Inactivation and covalent modification of CTP synthetase by thiourea dioxide.

    PubMed Central

    Robertson, J. G.; Sparvero, L. J.; Villafranca, J. J.

    1992-01-01

    Thiourea dioxide was used in chemical modification studies to identify functionally important amino acids in Escherichia coli CTP synthetase. Incubation at pH 8.0 in the absence of substrates led to rapid, time dependent, and irreversible inactivation of the enzyme. The second-order rate constant for inactivation was 0.18 M-1 s-1. Inactivation also occurred in the absence of oxygen and in the presence of catalase, thereby ruling out mixed-function oxidation/reduction as the mode of amino acid modification. Saturating concentrations of the substrates ATP and UTP, and the allosteric activator GTP prevented inactivation by thiourea dioxide, whereas saturating concentrations of glutamine (a substrate) did not. The concentration dependence of nucleotide protection revealed cooperative behavior with respect to individual nucleotides and with respect to various combinations of nucleotides. Mixtures of nucleotides afforded greater protection against inactivation than single nucleotides alone, and a combination of the substrates ATP and UTP provided the most protection. The Hill coefficient for nucleotide protection was approximately 2 for ATP, UTP, and GTP. In the presence of 1:1 ratios of ATP:UTP, ATP:GTP, and UTP:GTP, the Hill coefficient was approximately 4 in each case. Fluorescence and circular dichroism measurements indicated that modification by thiourea dioxide causes detectable changes in the structure of the protein. Modification with [14C]thiourea dioxide demonstrated that complete inactivation correlates with incorporation of 3 mol of [14C]thiourea dioxide per mole of CTP synthetase monomer. The specificity of thiourea dioxide for lysine residues indicates that one or more lysines are most likely involved in CTP synthetase activity. The data further indicate that nucleotide binding prevents access to these functionally important residues. PMID:1303749

  18. Irreversible thermodynamics of creep in crystalline solids

    NASA Astrophysics Data System (ADS)

    Mishin, Y.; Warren, J. A.; Sekerka, R. F.; Boettinger, W. J.

    2013-11-01

    We develop an irreversible thermodynamics framework for the description of creep deformation in crystalline solids by mechanisms that involve vacancy diffusion and lattice site generation and annihilation. The material undergoing the creep deformation is treated as a nonhydrostatically stressed multicomponent solid medium with nonconserved lattice sites and inhomogeneities handled by employing gradient thermodynamics. Phase fields describe microstructure evolution, which gives rise to redistribution of vacancy sinks and sources in the material during the creep process. We derive a general expression for the entropy production rate and use it to identify of the relevant fluxes and driving forces and to formulate phenomenological relations among them taking into account symmetry properties of the material. As a simple application, we analyze a one-dimensional model of a bicrystal in which the grain boundary acts as a sink and source of vacancies. The kinetic equations of the model describe a creep deformation process accompanied by grain boundary migration and relative rigid translations of the grains. They also demonstrate the effect of grain boundary migration induced by a vacancy concentration gradient across the boundary.

  19. Combustion irreversibilities: Numerical simulation and analysis

    NASA Astrophysics Data System (ADS)

    Silva, Valter; Rouboa, Abel

    2012-08-01

    An exergy analysis was performed considering the combustion of methane and agro-industrial residues produced in Portugal (forest residues and vines pruning). Regarding that the irreversibilities of a thermodynamic process are path dependent, the combustion process was considering as resulting from different hypothetical paths each one characterized by four main sub-processes: reactant mixing, fuel oxidation, internal thermal energy exchange (heat transfer), and product mixing. The exergetic efficiency was computed using a zero dimensional model developed by using a Visual Basic home code. It was concluded that the exergy losses were mainly due to the internal thermal energy exchange sub-process. The exergy losses from this sub-process are higher when the reactants are preheated up to the ignition temperature without previous fuel oxidation. On the other hand, the global exergy destruction can be minored increasing the pressure, the reactants temperature and the oxygen content on the oxidant stream. This methodology allows the identification of the phenomena and processes that have larger exergy losses, the understanding of why these losses occur and how the exergy changes with the parameters associated to each system which is crucial to implement the syngas combustion from biomass products as a competitive technology.

  20. Greenland's pronounced glacier retreat not irreversible

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2012-02-01

    In recent decades, the combined forces of climate warming and short-term variability have forced the massive glaciers that blanket Greenland into retreat, with some scientists worrying that deglaciation could become irreversible. The short history of detailed glacier observations, however, makes pinning the ice loss to either short-term dynamics or long-term change difficult. Research by Young et al. detailing the effects of two bouts of sudden and temporary cooling during an otherwise warm phase in Greenland's climate history could help answer that question by showing just how heavy a hand short-term variability can have in dictating glacier dynamics. Along the western edge of Greenland the massive Jakobshavn Isbræ glacier reaches out to the coast, its outflow dropping icebergs into Baffin Bay during the summer months. Flanking the glacier's tongue are the Tasiussaq and Marrait moraines—piles of rock marking the glacier's former extent. Researchers suspected the moraines were tied to two periods of abrupt cooling that hit Greenland 9300 and 8200 years ago, and that association was reinforced by the authors' radiocarbon and beryllium isotope analyses of the area surrounding the moraines. Beryllium-10 forms when cosmic radiation travels through the atmosphere and strikes the Earth's surface, with surface rock concentrations indicating how long it has been ice-free.

  1. Simulations of kinetically irreversible protein aggregate structure.

    PubMed Central

    Patro, S Y; Przybycien, T M

    1994-01-01

    We have simulated the structure of kinetically irreversible protein aggregates in two-dimensional space using a lattice-based Monte-Carlo routine. Our model specifically accounts for the intermolecular interactions between hydrophobic and hydrophilic protein surfaces and a polar solvent. The simulations provide information about the aggregate density, the types of inter-monomer contacts and solvent content within the aggregates, the type and extent of solvent exposed perimeter, and the short- and long-range order all as a function of (i) the extent of monomer hydrophobic surface area and its distribution on the model protein surface and (ii) the magnitude of the hydrophobic-hydrophobic contact energy. An increase in the extent of monomer hydrophobic surface area resulted in increased aggregate densities with concomitant decreased system free energies. These effects are accompanied by increases in the number of hydrophobic-hydrophobic contacts and decreases in the solvent-exposed hydrophobic surface area of the aggregates. Grouping monomer hydrophobic surfaces in a single contiguous stretch resulted in lower aggregate densities and lower short range order. More favorable hydrophobic-hydrophobic contact energies produced structures with higher densities but the number of unfavorable protein-protein contacts was also observed to increase; greater configurational entropy produced the opposite effect. Properties predicted by our model are in good qualitative agreement with available experimental observations. Images FIGURE 6 FIGURE 13 PMID:8061184

  2. Irreversible electroporation on the small intestine

    PubMed Central

    Phillips, M A; Narayan, R; Padath, T; Rubinsky, B

    2012-01-01

    Background: Non-thermal irreversible electroporation (NTIRE) has recently been conceived as a new minimally invasive ablation method, using microsecond electric fields to produce nanoscale defects in the cell membrane bilayer and induce cell death while keeping all other molecules, including the extracellular matrix, intact. Here, we present the first in vivo study that examines the effects of NTIRE on the small intestine, an organ whose collateral damage is of particular concern in the anticipated use of NTIRE for treatment of abdominal cancers. Methods: A typical NTIRE electrical protocol was applied directly to the rat small intestine and histological analysis was used to examine the effect of NTIRE over time. Results: The application of NTIRE led to complete cell ablation in the targeted tissue, but the animal did not show any physiological effects of the procedure and the intestine showed signs of recovery, developing an epithelial layer 3 days post treatment and regenerating its distinct layers within a week. Conclusion: Our results indicate that this novel procedure can be used for abdominal cancer treatment while minimising collateral damage to adjacent tissues because of the unique ability of the NTIRE ablation method to target the cell membrane. PMID:22223084

  3. Identification of new peptide amides as selective cathepsin L inhibitors: the first step towards selective irreversible inhibitors?

    PubMed

    Torkar, Ana; Lenarčič, Brigita; Lah, Tamara; Dive, Vincent; Devel, Laurent

    2013-05-15

    A small library of peptide amides was designed to profile the cathepsin L active site. Within the cathepsin family of cysteine proteases, the first round of selection was on cathepsin L and cathepsin B, and then selected hits were further evaluated for binding to cathepsin K and cathepsin S. Five highly selective sequences with submicromolar affinities towards cathepsin L were identified. An acyloxymethyl ketone warhead was then attached to these sequences. Although these original irreversible inhibitors inactivate cathepsin L, it appears that the nature of the warhead drastically impact the selectivity profile of the resulting covalent inhibitors.

  4. The Anesthetic Efficacy of the Intraosseous Injection in Irreversible Pulpitis.

    DTIC Science & Technology

    1995-01-01

    The purpose of this study was to evaluate the anesthetic efficacy of an intraosseous injection in teeth diagnosed with irreversible pulpitis . Fifty...one healthy human subjects with symptomatic maxillary or mandibular posterior teeth diagnosed with irreversible pulpitis were used in this study. The

  5. Guinea pig ductus arteriosus. II - Irreversible closure after birth.

    NASA Technical Reports Server (NTRS)

    Fay, F. S.; Cooke, P. H.

    1972-01-01

    To investigate the mechanism underlying irreversibility of ductal closure after birth, studies were undertaken to determine the exact time course for the onset of irreversible closure of the guinea pig ductus arteriosus. Parallel studies of the reactivity of ductal smooth muscle to oxygen and studies of the postpartum cellular changes within the vessel were also carried out.

  6. Recent advances in the uses and applications of ribosome-inactivating proteins from plants.

    PubMed

    Girbés, T; Ferreras, J M; Iglesias, R; Citores, L; De Torre, C; Carbajales, M L; Jiménez, P; De Benito, F M; Muñoz, R

    1996-06-01

    Plant ribosome-inactivating proteins (RIPs) are inhibitors present in all parts of plants that irreversibly inactivate eukaryotic ribosomes, thus impairing protein synthesis. RIPs are enzymes with N-glycosidase activity on the large rRNA. Their powerful inhibitory activity has been made use of advantageously to construct conjugates with suitable carriers targeted to altered specific cells. RIPs may be used to inhibit replication of both animal and plant viruses. The introduction of genes coding for RIPs into the genome of plants leads to an increase in resistance towards fungal pathogens and viruses. RIPs are important tools for the treatment of cancer and AIDS and for the protection of crop production.

  7. Irreversible Electroporation in a Swine Lung Model

    SciTech Connect

    Dupuy, Damian E.; Aswad, Bassam; Ng, Thomas

    2011-04-15

    Purpose: This study was designed to evaluate the safety and tissue effects of IRE in a swine lung model. Methods: This study was approved by the institutional animal care committee. Nine anesthetized domestic swine underwent 15 percutaneous irreversible electroporation (IRE) lesion creations (6 with bipolar and 3 with 3-4 monopolar electrodes) under fluoroscopic guidance and with pancuronium neuromuscular blockade and EKG gating. IRE electrodes were placed into the central and middle third of the right mid and lower lobes in all animals. Postprocedure PA and lateral chest radiographs were obtained to evaluate for pneumothorax. Three animals were sacrificed at 2 weeks and six at 4 weeks. Animals underwent high-resolution CT scanning and PA and lateral radiographs 1 h before sacrifice. The treated lungs were removed en bloc, perfused with formalin, and sectioned. Gross pathologic and microscopic changes after standard hematoxylin and eosin staining were analyzed within the areas of IRE lesion creation. Results: No significant adverse events were identified. CT showed focal areas of spiculated high density ranging in greatest diameter from 1.1-2.2 cm. On gross inspection of the sectioned lung, focal areas of tan discoloration and increased density were palpated in the areas of IRE. Histological analysis revealed focal areas of diffuse alveolar damage with fibrosis and inflammatory infiltration that respected the boundaries of the interlobular septae. No pathological difference could be discerned between the 2- and 4-week time points. The bronchioles and blood vessels within the areas of IRE were intact and did not show signs of tissue injury. Conclusion: IRE creates focal areas of diffuse alveolar damage without creating damage to the bronchioles or blood vessels. Short-term safety in a swine model appears to be satisfactory.

  8. Irreversible Sorption of Contaminants During Ferrihydrite Transformation

    SciTech Connect

    Anderson, H.L.; Arthur, S.E.; Brady, P.V.; Cygan, R.T.; Nagy, K.L.; Westrich, H.R.

    1999-05-19

    A better understanding of the fraction of contaminants irreversibly sorbed by minerals is necessary to effectively quantify bioavailability. Ferrihydrite, a poorly crystalline iron oxide, is a natural sink for sorbed contaminants. Contaminants may be sorbed/occluded as ferrihydrite precipitates in natural waters or as it ages and transforms to more crystalline iron oxides such as goethite or hematite. Laboratory studies indicate that Cd, Co, Cr, Cu, Ni, Np, Pb, Sr, U, and Zn are irreversibly sorbed to some extent during the aging and transformation of synthetic ferrihydrite. Barium, Ra and Sr are known to sorb on ferrihydrite in the pH range of 6 to 10 and sorb more strongly at pH values above its zero point of charge (pH> 8). We will review recent literature on metal retardation, including our laboratory and modeling investigation of Ba (as an analogue for Ra) and Sr adsorption/resorption, during ferrihydrite transformation to more crystalline iron oxides. Four ferrihydrite suspensions were aged at pH 12 and 50 °C with or without Ba in 0.01 M KN03 for 68 h or in 0.17 M KN03 for 3424 h. Two ferrihydrite suspensions were aged with and without Sr at pH 8 in 0.1 M KN03 at 70°C. Barium or Sr sorption, or resorption, was measured by periodically centrifuging suspension subsamples, filtering, and analyzing the filtrate for Ba or Sr. Solid subsamples were extracted with 0.2 M ammonium oxalate (pH 3 in the dark) and with 6 M HCl to determine the Fe and Ba or Sr attributed to ferrihydrite (or adsorbed on the goethite/hematite stiace) and the total Fe and Ba or Sr content, respectively. Barium or Sr occluded in goethite/hematite was determined by the difference between the total Ba or Sr and the oxalate extractable Ba or Sr. The percent transformation of ferrihydrite to goethite/hematite was estimated from the ratio of oxalate and HC1 extractable Fe. All Ba was retained in the precipitates for at least 20 h. Resorption of Ba reached a maximum of 7 to 8% of the Ba2+ added

  9. Inactivation and reactivation of B. megatherium phage.

    PubMed

    NORTHROP, J H

    1955-11-20

    Preparation of Reversibly Inactivated (R.I.) Phage.- If B. megatherium phage (of any type, or in any stage of purification) is suspended in dilute salt solutions at pH 5-6, it is completely inactivated; i.e., it does not form plaques, or give rise to more phage when mixed with a sensitive organism (Northrop, 1954). The inactivation occurs when the phage is added to the dilute salt solution. If a suspension of the inactive phage in pH 7 peptone is titrated to pH 5 and allowed to stand, the activity gradually returns. The inactivation is therefore reversible. Properties of R.I. Phage.- The R.I. phage is adsorbed by sensitive cells at about the same rate as the active phage. It kills the cells, but no active phage is produced. The R.I. phage therefore has the properties of phage "ghosts" (Herriott, 1951) or of colicines (Gratia, 1925), or phage inactivated by ultraviolet light (Luria, 1947). The R.I. phage is sedimented in the centrifuge at the same rate as active phage. It is therefore about the same size as the active phage. The R.I. phage is most stable in pH 7, 5 per cent peptone, and may be kept in this solution for weeks at 0 degrees C. The rate of digestion of R.I. phage by trypsin, chymotrypsin, or desoxyribonuclease is about the same as that of active phage (Northrop, 1955 a). Effect of Various Substances on the Formation of R.I. Phage.- There is an equilibrium between R.I. phage and active phage. The R.I. form is the stable one in dilute salt solution, pH 5 to 6.5 and at low temperature (<20 degrees C.). At pH >6.5, in dilute salt solution, the R.I. phage changes to the active form. The cycle, active right harpoon over left harpoon inactive phage, may be repeated many times at 0 degrees C. by changing the pH of the solution back and forth between pH 7 and pH 6. Irreversible inactivation is caused by distilled water, some heavy metals, concentrated urea or quanidine solutions, and by l-arginine. Reversible inactivation is prevented by all salts tested (except

  10. Inactivation of biofilm bacteria.

    PubMed Central

    LeChevallier, M W; Cawthon, C D; Lee, R G

    1988-01-01

    The current project was developed to examine inactivation of biofilm bacteria and to characterize the interaction of biocides with pipe surfaces. Unattached bacteria were quite susceptible to the variety of disinfectants tested. Viable bacterial counts were reduced 99% by exposure to 0.08 mg of hypochlorous acid (pH 7.0) per liter (1 to 2 degrees C) for 1 min. For monochloramine, 94 mg/liter was required to kill 99% of the bacteria within 1 min. These results were consistent with those found by other investigators. Biofilm bacteria grown on the surfaces of granular activated carbon particles, metal coupons, or glass microscope slides were 150 to more than 3,000 times more resistant to hypochlorous acid (free chlorine, pH 7.0) than were unattached cells. In contrast, resistance of biofilm bacteria to monochloramine disinfection ranged from 2- to 100-fold more than that of unattached cells. The results suggested that, relative to inactivation of unattached bacteria, monochloramine was better able to penetrate and kill biofilm bacteria than free chlorine. For free chlorine, the data indicated that transport of the disinfectant into the biofilm was a major rate-limiting factor. Because of this phenomenon, increasing the level of free chlorine did not increase disinfection efficiency. Experiments where equal weights of disinfectants were used suggested that the greater penetrating power of monochloramine compensated for its limited disinfection activity. These studies showed that monochloramine was as effective as free chlorine for inactivation of biofilm bacteria. The research provides important insights into strategies for control of biofilm bacteria. Images PMID:2849380

  11. Suicide inactivation of catechol 2,3-dioxygenase from Pseudomonas putida mt-2 by 3-halocatechols

    SciTech Connect

    Bartels, I.; Knackmuss, H.J.; Reineke, W.

    1984-03-01

    The inactivation of catechol 2,3-dioxygenase from Pseudomonas putida mt-2 by 3-chloro- and 3-fluorocatechol and the iron-chelating agent Tiron (catechol-3,5-disulfonate) was studied. Whereas inactivation by Tiron is an oxygen-independent and mostly reversible process, inactivation by the 3-halocatechols was only observed in the presence of oxygen and was largely irreversible. The rate constants for inactivation (K/sub 2/) were 1.62 x 10/sup -3/ sec/sup -1/ for 3-chlorocatechol and 2.38 x 10/sup -3/ sec/sup -1/ for 3-fluorocatechol. The inhibitor constants (K/sub i/) were 23 ..mu..M for 3-chlorocatechol and 17 ..mu..M for 3-fluorocatechol. The kinetic data for 3-fluorocatechol could only be obtained in the presence of 2-mercaptoethanol. Besides inactivated enzyme, some 2-hydroxyhexa-2,4-dienoic acid as the actual suicide product of meta-cleavage. A side product of 3-fluorocatechol cleavage is a yellow compound with the spectral characteristics of a 2-hydroxy-6-oxohexa-2,4-dienoci acid indicating 1,6-cleavage. Rates of inactivation by 3-fluorocatechol were reduced in the presence of superoxide dismutase, catalase, formate, and mannitol, which implies that superoxide anion, hydrogen peroxide, and hydroxyl radical exhibit additional inactivation. 64 references.

  12. Irreversibility transition of colloidal polycrystals under cyclic deformation

    PubMed Central

    Jana, Pritam Kumar; Alava, Mikko J.; Zapperi, Stefano

    2017-01-01

    Cyclically loaded disordered particle systems, such as granular packings and amorphous media, display a non-equilibrium phase transition towards irreversibility. Here, we investigate numerically the cyclic deformation of a colloidal polycrystal with impurities and reveal a transition to irreversible behavior driven by the displacement of dislocations. At the phase transition we observe enhanced particle diffusion, system size effects and broadly distributed strain bursts. In addition to provide an analogy between the deformation of amorphous and polycrystalline materials, our results allow to reinterpret Zener pinning of grain boundaries as a way to prevent the onset of irreversible crystal ordering. PMID:28358018

  13. Inactivation of pectin methylesterase by immobilized trypsins from cunner fish and bovine pancreas.

    PubMed

    Li, Dan; Matos, Madyu; Simpson, Benjamin K

    2013-01-01

    Immobilized cunner fish trypsin was used to inactivate pectin methylesterase (PME). The effects of different reaction conditions (e.g., incubation time, PME concentration, and temperature) on PME inactivation and kinetics of inactivation were investigated. Temperature, incubation time, and PME concentration significantly affected the extent of PME inactivation. Generally, higher temperature, longer incubation time, and low PME concentration caused more PME inactivation. The immobilized fish trypsin had higher capacity to inactivate PME than immobilized bovine trypsin. The inactivation efficiency of the immobilized fish trypsin was about 20% higher than that of its bovine counterpart. However, PME inactivated by both trypsins regained partial activity during storage at 4°C, with immobilized fish trypsin-treated PME regaining more of its original activity than the immobilized bovine trypsin-treated PME. Heat-denatured PME was hydrolyzed more extensively by immobilized fish trypsin than by its bovine counterpart. The rate constants increased, whereas the D-values decreased with temperature for both immobilized fish and bovine trypsins. The inactivation rate constants of immobilized fish trypsin at all the temperatures investigated (i.e., 15-35°C) were higher than those of immobilized bovine trypsin. Furthermore, the activation energy (Ea ) of PME inactivation by immobilized fish trypsin was lower than that of immobilized bovine trypsin.

  14. Ultrarapid delayed rectifier current inactivation in human atrial myocytes: properties and consequences.

    PubMed

    Feng, J; Xu, D; Wang, Z; Nattel, S

    1998-11-01

    The ultrarapid delayed rectifier current (IK,ur) plays a significant role in human atrial repolarization and is generally believed to show little rate dependence because of slow and partial inactivation. This study was designed to evaluate in detail the properties and consequences of IK,ur inactivation in isolated human atrial myocytes. IK,ur inactivated with a biexponential time course and a half-inactivation voltage of -7.5 +/- 0.6 mV (mean +/- SE), with complete inactivation during 50-s pulses to voltages positive to +10 mV (37 degreesC). Recovery from inactivation proceeded slowly, with time constants of 0.42 +/- 0.06 and 7.9 +/- 0.9 s at -80 mV (37 degreesC). Substantial frequency dependence was observed at 37 degreesC over a clinically relevant range of frequencies. Inactivation was faster and occurred at more positive voltages at 37 degreesC compared with room temperature. The voltage and time dependencies of Kv1.5 inactivation were studied in Xenopus oocytes to avoid overlapping currents and strongly resembled those of IK,ur in native myocytes. We conclude that, while IK,ur inactivation is slow, it is extensive, and slow recovery from inactivation confers important frequency dependence with significant consequences for understanding the role of IK,ur in human atrial repolarization.

  15. Fourteen. beta. -(bromoacetamido)morphine irreversibly labels. mu. opioid receptors in rat brain membranes

    SciTech Connect

    Bidlack, J.M.; Frey, D.K.; Seyed-Mozaffari, A.; Archer, S. )

    1989-05-16

    The binding properties of 14{beta}-(bromoacetamido)morphine (BAM) and the ability of BAM to irreversibly inhibit opioid binding to rat brain membranes were examined to characterize the affinity and selectivity of BAM as an irreversible affinity ligand for opioid receptors. BAM had the same receptor selectivity as morphine, with a 3-5-fold decrease in affinity for the different types of opioid receptors. When brain membranes were incubated with BAM, followed by extensive washing, opioid binding was restored to control levels. However, when membranes were incubated with dithiothreitol (DTT), followed by BAM, and subsequently washed, 90% of the 0.25 nM ({sup 3}H)(D-Ala{sup 2},(Me)Phe{sup 4},Gly(ol){sup 5})enkephalin (DAGO) binding was irreversibly inhibited as a result of the specific alkylation of a sulfhydryl group at the {mu} binding site. This inhibition was dependent on the concentrations of both DTT and BAM. The {mu} receptor specificity of BAM alkylation was demonstrated by the ability of BAM alkylated membranes to still bind the {delta}-selective peptide ({sup 3}H)(D-penicillamine{sup 2},D-penicillamine{sup 5})enkephalin (DPDPE) and (-)-({sup 3}H)bremazocine in the presence of {mu} and {delta} blockers, selective for {kappa} binding sites. Morphine and naloxone partially protected the binding site from alkylation with BAM, while ligands that did not bind to the {mu}s site did not afford protection. These studies have demonstrated that when a disulfide bond at or near {mu} opioid binding sites was reduced, BAM could then alkylate this site, resulting in the specific irreversible labeling of {mu} opioid receptors.

  16. Irreversibility and dissipation in finite-state automata

    NASA Astrophysics Data System (ADS)

    Ganesh, Natesh; Anderson, Neal G.

    2013-12-01

    Irreversibility and dissipation in finite-state automata (FSA) are considered from a physical-information-theoretic perspective. A quantitative measure for the computational irreversibility of finite automata is introduced, and a fundamental lower bound on the average energy dissipated per state transition is obtained and expressed in terms of FSA irreversibility. The irreversibility measure and energy bound are germane to any realization of a deterministic automaton that faithfully registers abstract FSA states in distinguishable states of a physical system coupled to a thermal environment, and that evolves via a sequence of interactions with an external system holding a physical instantiation of a random input string. The central result, which is shown to follow from quantum dynamics and entropic inequalities alone, can be regarded as a generalization of Landauer's Principle applicable to FSAs and tailorable to specified automata. Application to a simple FSA is illustrated.

  17. Microscopic reversibility and macroscopic irreversibility: A lattice gas model

    NASA Astrophysics Data System (ADS)

    Pérez-Cárdenas, Fernando C.; Resca, Lorenzo; Pegg, Ian L.

    2016-09-01

    We present coarse-grained descriptions and computations of the time evolution of a lattice gas system of indistinguishable particles, whose microscopic laws of motion are exactly reversible, in order to investigate how or what kind of macroscopically irreversible behavior may eventually arise. With increasing coarse-graining and number of particles, relative fluctuations of entropy rapidly decrease and apparently irreversible behavior unfolds. Although that behavior becomes typical in those limits and within a certain range, it is never absolutely irreversible for any individual system with specific initial conditions. Irreversible behavior may arise in various ways. We illustrate one possibility by replacing detailed integer occupation numbers at lattice sites with particle probability densities that evolve diffusively.

  18. Irreversible adsorption/desorption of PAHs in sediment/water

    SciTech Connect

    Fu, G.; Kan, A.T.; Tomson, M.B.

    1996-10-01

    Successive adsorption isotherm of phenanthrene on soil corresponds to a constant partition of phenanthrene between the bulk solution and solid phase. This shows that the hydrophobic reaction is a dominant mechanism in adsorption process. However, desorption of PAHs appears irreversibility. Cyclic and multiple adsorption and desorption experiments indicated that there is an irreversibly adsorbed intrinsic capacity in the interaction of PAHs (naphthalene and phenanthrene) and soil in aqueous solution. This irreversible fraction for PAHs (naphthalene and phenanthrene) is about 1000-5000 {mu}g/g normalized on the basis of soil organic carbon. The desorption of PAHs from soil appears biphasic when the total adsorbed capacity is greater than the intrinsic irreversibly adsorbed value. In phase, the partitioning coefficient of desorption of PAHs is similar to that of adsorption. However, the other mechanism may be responsible to control the release of PAHs in phase 2.

  19. Gibbs Paradox Revisited from the Fluctuation Theorem with Absolute Irreversibility

    NASA Astrophysics Data System (ADS)

    Murashita, Yûto; Ueda, Masahito

    2017-02-01

    The inclusion of the factor ln (1 /N !) in the thermodynamic entropy proposed by Gibbs is shown to be equivalent to the validity of the fluctuation theorem with absolute irreversibility for gas mixing.

  20. Ecological optimization of an irreversible harmonic oscillators Carnot heat engine

    NASA Astrophysics Data System (ADS)

    Liu, Xiaowei; Chen, Lingen; Wu, Feng; Sun, Fengrui

    2009-12-01

    A model of an irreversible quantum Carnot heat engine with heat resistance, internal irreversibility and heat leakage and many non-interacting harmonic oscillators is established in this paper. Based on the quantum master equation and semi-group approach, equations of some important performance parameters, such as power output, efficiency, exergy loss rate and ecological function for the irreversible quantum Carnot heat engine are derived. The optimal ecological performance of the heat engine in the classical limit is analyzed with numerical examples. Effects of internal irreversibility and heat leakage on the ecological performance are discussed. A performance comparison of the quantum heat engine under maximum ecological function and maximum power conditions is also performed.

  1. Recovery of prostacyclin synthesis in vascular smooth muscle cells following self-inactivation and requirement for growth factors

    SciTech Connect

    Bailey, J.M.; Hla, T.T.; Pash, J.M.

    1986-05-01

    The cyclooxygenase enzyme system is a prime example of a metabolic pathway that is regulated by self inactivation. This is believed to occur in part via the irreversible reaction of the endoperoxide intermediate species with the cyclooxygenase enzyme. This inactivation and recovery of activity is similar to the inactivation observed with aspirin which irreversibly acetylates the enzyme. Self inactivation was studied in cultured rat and bovine aorta smooth muscle cells. The production of the prostanoid PGI2 was demonstrated by incubation of a monolayer of cells with 12 ..mu..M C-14 labeled arachidonic acid. Products were analyzed by thin layer chromatography and identified by their comigration with authentic standards and confirmed by gas chromatography/mass spectrometry. Preincubation of the cells for 10 minutes with arachidonic acid at concentrations as low as 1 ..mu..g/mL inactivated the cells to a second challenge with radiolabeled arachidonic acid. Recovery from self inactivation took place over a three hour time period and was similar to the recovery observed with aspirin pretreatment. Recovery was inhibited by addition of 10 ..mu..g/mL cycloheximide to the medium indicating that it involves synthesis of cyclooxygenase protein. Epidermal growth factor was identified as a serum factor responsible for the rapid recovery of cyclooxygenase activity in rat and bovine aorta smooth muscle cells.

  2. Irreversible pulpitis and achieving profound anesthesia: Complexities and managements

    PubMed Central

    Modaresi, Jalil; Davoudi, Amin; Badrian, Hamid; Sabzian, Roya

    2016-01-01

    Dental pain management is one of the most critical aspects of modern dentistry. Irreversible pulpitis and further root canal therapy might cause an untolerated pain to the patients. The improvements in anesthetic agents and techniques were one of the advantages of studying nerve biology and stimulation. This article tried to overview of the nerve activities in inflammatory environments or induced pain. Furthermore, the proper advises, and supplementary techniques were reviewed for better pain management of irreversible pulpitis. PMID:26957681

  3. Optimization of Irreversible Cogeneration Systems under Alternative Performance Criteria

    NASA Astrophysics Data System (ADS)

    Atmaca, M.; Gumus, M.; Inan, A. T.; Yilmaz, T.

    2009-10-01

    In this study, an exergy optimization has been performed for a cogeneration plant consisting of an irreversible Carnot heat engine. In the analysis, different objective functions have been defined based on alternative performance criteria and the optimum values of the design parameters of a cogeneration cycle were determined for different criteria. In this context, the effects of irreversibilities on the exergetic performance are investigated, and the results are discussed.

  4. The incidence of mechanical allodynia in patients with irreversible pulpitis.

    PubMed

    Owatz, Christopher B; Khan, Asma A; Schindler, William G; Schwartz, Scott A; Keiser, Karl; Hargreaves, Kenneth M

    2007-05-01

    The mechanisms of odontogenic pain are complex and incompletely understood. Cases of irreversible pulpitis are thought to represent a localized inflammatory response to bacterial challenge in dental pulp tissue. The presenting symptoms are classically defined by exaggerated painful episodes to thermal stimuli that may linger after cessation of the stimulus. However, the associated incidence of mechanical allodynia, defined as reduced mechanical pain threshold to masticatory forces, has not been characterized. This study evaluated pain intensity ratings and the presence of mechanical allodynia reported by 993 consecutive dental patients presenting for tooth extraction in a community health center. After clinical and radiographic examinations, the pulpal/periradicular diagnostic categories were normal pulp/normal periradicular (n=792 patients), irreversible pulpitis/normal periradicular (n=86), or irreversible pulpitis/acute periradicular periodontitis (n=115). The rank order for the mean values of pain intensity ratings was irreversible pulpitis/acute periradicular periodontitis > irreversible pulpitis/normal periradicular > normal/normal (p<0.05 for all comparisons). The incidence of mechanical allodynia in patients presenting with irreversible pulpitis was 57.2%, indicating that periradicular mechanical allodynia contributes to early stages of odontogenic pain because of inflammation of vital pulpal tissue.

  5. Inactivation of Microorganisms

    NASA Astrophysics Data System (ADS)

    Alzamora, Stella Maris; Guerrero, Sandra N.; Schenk, Marcela; Raffellini, Silvia; López-Malo, Aurelio

    Minimal processing techniques for food preservation allow better retention of product flavor, texture, color, and nutrient content than comparable conventional treatments. A wide range of novel alternative physical factors have been intensely investigated in the last two decades. These physical factors can cause inactivation of microorganisms at ambient or sublethal temperatures (e.g., high hydrostatic pressure, pulsed electric fields, ultrasound, pulsed light, and ultraviolet light). These technologies have been reported to reduce microorganism population in foods while avoiding the deleterious effects of severe heating on quality. Among technologies, high-energy ultrasound (i.e., intensities higher than 1 W/cm2, frequencies between 18 and 100 kHz) has attracted considerable interest for food preservation applications (Mason et al., 1996; Povey and Mason, 1998).

  6. Long-term hydroxytamoxifen treatment of an MCF-7-derived breast cancer cell line irreversibly inhibits the expression of estrogenic genes through chromatin remodeling.

    PubMed

    Badia, E; Duchesne, M J; Semlali, A; Fuentes, M; Giamarchi, C; Richard-Foy, H; Nicolas, J C; Pons, M

    2000-08-01

    Antiestrogen resistance is frequently observed in patients after longterm treatment with tamoxifen, a nonsteroidal antiestrogen widely used for endocrine therapy of breast cancer. In vitro studies in resistant cells showed that the expression of natural estrogen-responsive genes is frequently altered. Using MVLN cells, an MCF-7-derived cell model, we previously demonstrated that 4-hydroxytamoxifen (OHT) treatment irreversibly inactivated an estrogen-regulated chimeric luciferase response by a direct effect of the drug and not through a cell selection process (E. Badia et al., Cancer Res., 54: 5860-5866, 1994). In the present study, we present tamoxifen-resistant but still estrogen-dependent clones isolated after long-term treatment of MVLN cells with OHT and show that progesterone receptor (PR) expression was irreversibly decreased in some of these clones, whereas the PRA:PRB ratio of residual PR remained unchanged. The irreversible inactivation of both chimeric luciferase gene and PR gene expression was associated with the disappearance of DNase 1-hypersensitive sites. In the case of the chimeric gene, at least one of these sites was close to the estrogen responsive element. Genomic sequencing analysis of a clone with very low PR content did not reveal any methylation on CpG dinucleotides or any mutation in the PR gene promoter region. In all of the resistant clones tested and independently of their PR content, estrogen receptor expression was only lowered by half and remained functional, whereas pS2 expression was not modified. We also observed that the residual luciferase activity level (1-2%) of the MVLN clones, the luciferase expression of which had been irreversibly inactivated, was raised 4-fold by trichostatin A treatment. We conclude that long-term OHT treatment may modify the chromatin structure and thus could contribute to differentially silencing natural target genes.

  7. [Mechanisms for protecting nitrogenase from inactivation by oxygen].

    PubMed

    Soto-Urzúa, L; Baca, B E

    2001-01-01

    The biological fixation of dinitrogen is the most important way to access of N to organisms, this process requires a fairly high proportion of the ATP; which is generated in the course of respiratory electron transport reactions with O2 as electron acceptor. The Nitrogenase enzyme complex (the nitrogen. fixing enzyme) is sensitive to O2, that irreversible inactivates the enzyme. Diazotrophs must employ mechanisms which, on the other hand, permit the supply of O2 required for energy regeneration and protect Nase from the deleterious effect of O2. They have developed several strategies for limiting O2 access to Nase: 1).--It could avoid O2 and live in environments which are permanently anaerobic, 2).--Alternatively, it could generate a physical barrier around its Nase and in this way prevent O2 from diffusing to the enzyme, 3).--The microorganism could, by its metabolism, reduce the concentration of O2 within the vicinity of Nasa, 4).--They could modify its Nasa in such manner as to render it resistant to inactivation by O2 (conformational protection). 5).--Finally, the microorganism could simply balance Nasa inactivation with the synthesis of new enzyme. In this article we examine the antipathy between Nasa and O2, particularly with strict aerobic and photosynthetic microorganisms.

  8. Thermal stability of Artemia HGPRT: effect of substrates on inactivation kinetics.

    PubMed

    Montero, C; Llorente, P; Argomaniz, L; Menendez, M

    1996-06-01

    Hypoxanthine-guanine phosphoribosyltransferase (HGPRT, E.C.2.4.2.8) from Artemia cysts exhibits maximum activity at 70 degrees C. Its thermal stability has been examined following enzymatic activity as a function of temperature. Cold-induced renaturation experiments of samples heated at increasing temperatures showed that reversibility of thermal inactivation depends on the incubation time and final temperature. Prolonged incubation of the thermoinactivated enzyme at 0 degree C did not afford any further increase of the catalytic activity at 37 degrees C. The complex substrate PRPP:Mg protects HGPRT from thermal inactivation. However, incubations with hypoxanthine rendered a less thermostable enzyme at any temperature tested. The irreversible inactivation of HGPRT proceeds in two exponential steps. The analysis of the apparent rate constants for the fast and the slow phases, lambda 1 and lambda 2 as per the Lumry and Eyring model suggests the existence of more than three states in the thermal denaturation pathway of the free enzyme. In the presence of PRPP:Mg the irreversible process follows a single exponential and proceeds very slowly below 70 degrees C. PRPP:Mg also protects the enzyme from inactivation by NEM and pCMB, suggesting that -SH groups may be in the vicinity of the active site.

  9. Comparative thermal inactivation analysis of Aspergillus oryzae and Thiellavia terrestris cutinase: Role of glycosylation.

    PubMed

    Shirke, Abhijit N; Su, An; Jones, J Andrew; Butterfoss, Glenn L; Koffas, Mattheos A G; Kim, Jin Ryoun; Gross, Richard A

    2017-01-01

    Cutinase thermostability is important so that the enzymes can function above the glass transition of what are often rigid polymer substrates. A detailed thermal inactivation analysis was performed for two well-characterized cutinases, Aspergillus oryzae Cutinase (AoC) and Thiellavia terrestris Cutinase (TtC). Both AoC and TtC are prone to thermal aggregation upon unfolding at high temperature, which was found to be a major reason for irreversible loss of enzyme activity. Our study demonstrates that glycosylation stabilizes TtC expressed in Pichia pastoris by inhibiting its thermal aggregation. Based on the comparative thermal inactivation analyses of non-glycosylated AoC, glycosylated (TtC-G), and non-glycosylated TtC (TtC-NG), a unified model for thermal inactivation is proposed that accounts for thermal aggregation and may be applicable to other cutinase homologues. Inspired by glycosylated TtC, we successfully employed glycosylation site engineering to inhibit AoC thermal aggregation. Indeed, the inhibition of thermal aggregation by AoC glycosylation was greater than that achieved by conventional use of trehalose under a typical condition. Collectively, this study demonstrates the excellent potential of implementing glycosylation site engineering for thermal aggregation inhibition, which is one of the most common reasons for the irreversible thermal inactivation of cutinases and many proteins. Biotechnol. Bioeng. 2017;114: 63-73. © 2016 Wiley Periodicals, Inc.

  10. [Nourseothricin (streptothricin) inactivated by plasmid pIE 636-encoded acetyltransferase: detection of N-acetyl-beta-lysine in the inactivated product].

    PubMed

    Seltmann, G

    1985-12-01

    Nourseothricin (streptothricin) can be inactivated by an acetyl transferase synthesized by E. coli strains containing plasmid pIE 636. Nourseothricin inactivated in the presence of 14C-acetyl-coenzyme A was purified and submitted to partial acidic hydrolysis. By electrophoresis of the hydrolysate a 14C-containing substance moving only slowly towards the cathode could be isolated. This substance after complete hydrolysis yields only unlabelled beta-lysine.

  11. Attribution of irreversible loss to anthropogenic climate change

    NASA Astrophysics Data System (ADS)

    Huggel, Christian; Bresch, David; Hansen, Gerrit; James, Rachel; Mechler, Reinhard; Stone, Dáithí; Wallimann-Helmer, Ivo

    2016-04-01

    The Paris Agreement (2015) under the UNFCCC has anchored loss and damage in a separate article which specifies that understanding and support should be enhanced in areas addressing loss and damage such as early warning, preparedness, insurance and resilience. Irreversible loss is a special category under loss and damage but there is still missing clarity over what irreversible loss actually includes. Many negative impacts of climate change may be handled or mitigated by existing risk management, reduction and absorption approaches. Irreversible loss, however, is thought to be insufficiently addressed by risk management. Therefore, countries potentially or actually affected by irreversible loss are calling for other measures such as compensation, which however is highly contested in international climate policy. In Paris (2015) a decision was adopted that loss and damage as defined in the respective article of the agreement does not involve compensation and liability. Nevertheless, it is likely that some sort of mechanism will eventually need to come into play for irreversible loss due to anthropogenic climate change, which might involve compensation, other forms of non-monetary reparation, or transformation. Furthermore, climate litigation has increasingly been attempted to address negative effects of climate change. In this context, attribution is important to understand the drivers of change, what counts as irreversible loss due to climate change, and, possibly, who or what is responsible. Here we approach this issue by applying a detection and attribution perspective on irreversible loss. We first analyze detected climate change impacts as assessed in the IPCC Fifth Assessment Report. We distinguish between irreversible loss in physical, biological and human systems, and accordingly identify the following candidates of irreversible loss in these systems: loss of glaciers and ice sheets, loss of subsurface ice (permafrost) and related loss of lake systems; loss

  12. Irreversible stimulation of adenylate cyclase activity of fat cell membranes of phosphoramidate and phosphonate analogs of GTP.

    PubMed

    Cuatrecasas, P; Bennett, V; Jacobs, S

    1975-01-01

    The ability of 5'-guanylylimidodiphosphate (Gpp(NH)p) to stimulate irreversibly the adenylate cyclease activity of fat cell membranes has been studied by preincubating the membranes with this or related analogs followed by assaying after thoroughly washing the membranes. Activation can occur in a simple Tris-HCl buffer, in the absence of added divalent cations and in the presence of EDTA. Dithiothreitol enhances the apparent degree of activation, perhaps by stabilization. The importance of utilizing optimal conditions for stabilizing enzyme activity, and of measuring the simultaneous changes in the control enzyme, is illustrated. The organomercurial, p-aminophenylmercuric acetate, inhibits profoundly the activity of the native as well as the Gpp(NH)p-stimulated adenylate cyclase, but in both cases subsequent exposure to dithiothreitol restores fully the original enzyme activity. However, the mercurial-inactivated enzyme does not react with Gpp(NP)p, as evidenced by the subsequent restoration of only the control enzyme activity upon exposure to dithiothreitol. Thus, reaction with Gpp(NH)p requires intact sulfhydryl groups, but the activated state is not irreversibly destroyed by the inactivation caused by sulfhydryl blockade. GTP and, less effectively, GDP and ATP inhibit activation by Gpp(NH)p, but interpretations are complicated by the facts that this inhibition is overcome with time and that GTP and ATP can protect potently from spontaneous inactivation. These two nucleotides can be used in the Gpp(NH)p preincubation to stabilize the enzyme. The Gpp(NH)p-activated enzyme cannot be reversed spontaneously during prolonged incubation at 30 degrees C in the absence or presence of GTP, ATP, MgCl2, glycine, dithiothreitol, NaF or EDTA. The strong nucleophile, neutral hydroxylamine, decreases the Gpp(NH)p-activated enzyme activity and no subsequent activation is detected upon re-exposure to the nucleotide.

  13. Imperatorin is a mechanism-based inactivator of CYP2B6.

    PubMed

    Zheng, Liwei; Cao, Jiaojiao; Lu, Dan; Ji, Lin; Peng, Ying; Zheng, Jiang

    2015-01-01

    Imperatorin (IMP) is the major active ingredient in many common medicinal herbs. We examined the irreversible inhibitory effect of IMP on CYP2B6. IMP produced a time- and concentration-dependent inactivation of CYP2B6. About 70% of activity of CYP2B6 was suppressed after its incubation with 1.5 μM IMP for 9 minutes. KI and kinact were found to be 0.498 μM and 0.079 min(-1), respectively. The loss of CYP2B6 activity required the presence of NADPH. Glutathione and catalase/superoxide dismutase showed little protection against the IMP-induced enzyme inactivation. Ticlopidine, a substrate of CYP2B6, showed protection of the enzyme against the inactivation induced by IMP. The estimated partition ratio of the inactivation was approximately 4. Additionally, a γ-ketoenal intermediate was identified in microsomal incubations with IMP. CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, CYP3A4, and CYP3A5 were found to be involved in bioactivation of IMP. In conclusion, IMP is a mechanism-based inactivator of CYP2B6. The formation of γ-ketoenal intermediate may account for the enzyme inactivation.

  14. INACTIVATION OF SEXUAL AGGLUTINATION IN HANSENULA WINGEI AND SACCHAROMYCES KLUYVERI BY DISULFIDE-CLEAVING AGENTS.

    PubMed

    TAYLOR, N W

    1964-10-01

    Taylor, Neil W. (Northern Regional Research Laboratory, Peoria, Ill.). Inactivation of sexual agglutination in Hansenula wingei and Saccharomyces kluyveri by disulfide-cleaving agents. J. Bacteriol. 88:929-936. 1964.-Mating types of both Hansenula wingei and Saccharomyces kluyveri can be activated to produce uniformly strong sexual agglutination by treatments with various solvents, such as 8 m LiBr. The strongly agglutinative mating-type preparations were irreversibly inactivated for sexual agglutination by various chemical treatments. Type 5 of H. wingei was inactivated by disulfide-cleaving reagents, but type 21 of H. wingei was not. Type 3 of S. kluyveri was more sensitive than type 26 of S. kluyveri to inactivation by disulfide-cleaving reagents. Comparison of sensitivities to these and other treatments, plus a moderately strong cross-agglutination between type 3 and type 21, indicated that the sexually agglutinative elements on type 3 are similar to type 5, and those of type 21 are similar to those of type 26. Inactivation-rate experiments showed a loss of agglutinative ability according to a sigmoid decrement with time for both types 5 and 21. The apparent extent of inactivation depended markedly on agglutination test conditions. Results of these experiments were interpreted to indicate tentatively, first, that the agglutinative elements of both types of a species are proteins and, second, that several agglutinating linkages are formed between any two cells in sexual agglutination.

  15. Cyclooxygenase inactivation kinetics during reaction of prostaglandin H synthase-1 with peroxide.

    PubMed

    Wu, Gang; Kulmacz, Richard J; Tsai, Ah-Lim

    2003-11-25

    The peroxidase and cyclooxygenase activities of prostaglandin H synthase-1 (PGHS-1) both become irreversibly inactivated during reaction with peroxide. Sequential stopped-flow absorbance measurements with a chromogenic peroxidase cosubstrate previously were used to evaluate the kinetics of peroxidase inactivation during reaction of PGHS-1 with peroxide [Wu, G., et al. (1999) J. Biol. Chem. 274, 9231-7]. This approach has now been adapted to use a chromogenic cyclooxygenase substrate to analyze the detailed kinetics of cyclooxygenase inactivation during reaction of PGHS-1 with several hydroperoxides. In the absence of added reducing cosubstrates, which maximizes the levels of oxidized enzyme intermediates expected to lead to inactivation, cyclooxygenase activity was lost as fast as, or somewhat faster than, peroxidase activity. Cyclooxygenase inactivation kinetics appeared to be sensitive to the structure of the peroxide used. The addition of reducing cosubstrate during reaction of PGHS-1 with peroxide protected the peroxidase activity to a much greater degree than the cyclooxygenase activity. The results suggest a new concept of PGHS inactivation: that distinct damage can occur at the two active sites during side reactions of Intermediate II, which forms during reaction of PGHS with peroxide and which contains two oxidants, a ferryl heme in the peroxidase site, and a tyrosyl free radical in the cyclooxygenase site.

  16. Irreversible climate change due to carbon dioxide emissions

    PubMed Central

    Solomon, Susan; Plattner, Gian-Kasper; Knutti, Reto; Friedlingstein, Pierre

    2009-01-01

    The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility. This paper shows that the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop. Following cessation of emissions, removal of atmospheric carbon dioxide decreases radiative forcing, but is largely compensated by slower loss of heat to the ocean, so that atmospheric temperatures do not drop significantly for at least 1,000 years. Among illustrative irreversible impacts that should be expected if atmospheric carbon dioxide concentrations increase from current levels near 385 parts per million by volume (ppmv) to a peak of 450–600 ppmv over the coming century are irreversible dry-season rainfall reductions in several regions comparable to those of the “dust bowl” era and inexorable sea level rise. Thermal expansion of the warming ocean provides a conservative lower limit to irreversible global average sea level rise of at least 0.4–1.0 m if 21st century CO2 concentrations exceed 600 ppmv and 0.6–1.9 m for peak CO2 concentrations exceeding ≈1,000 ppmv. Additional contributions from glaciers and ice sheet contributions to future sea level rise are uncertain but may equal or exceed several meters over the next millennium or longer. PMID:19179281

  17. Irreversible climate change due to carbon dioxide emissions.

    PubMed

    Solomon, Susan; Plattner, Gian-Kasper; Knutti, Reto; Friedlingstein, Pierre

    2009-02-10

    The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility. This paper shows that the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop. Following cessation of emissions, removal of atmospheric carbon dioxide decreases radiative forcing, but is largely compensated by slower loss of heat to the ocean, so that atmospheric temperatures do not drop significantly for at least 1,000 years. Among illustrative irreversible impacts that should be expected if atmospheric carbon dioxide concentrations increase from current levels near 385 parts per million by volume (ppmv) to a peak of 450-600 ppmv over the coming century are irreversible dry-season rainfall reductions in several regions comparable to those of the "dust bowl" era and inexorable sea level rise. Thermal expansion of the warming ocean provides a conservative lower limit to irreversible global average sea level rise of at least 0.4-1.0 m if 21st century CO(2) concentrations exceed 600 ppmv and 0.6-1.9 m for peak CO(2) concentrations exceeding approximately 1,000 ppmv. Additional contributions from glaciers and ice sheet contributions to future sea level rise are uncertain but may equal or exceed several meters over the next millennium or longer.

  18. A criterion to maximize the irreversible efficiency in heat engines

    NASA Astrophysics Data System (ADS)

    Aragón-González, G.; Canales-Palma, A.; León-Galicia, A.; Musharrafie-Martínez, M.

    2003-02-01

    The purpose of this work is to obtain a more precise calculation of the effective limits to the efficiency, of several cyclic heat engines. This calculation is based, first, on the equations describing the irreversible efficiency, and second, on a method which results from a general criterion to maximize this efficiency, applicable to several heat engines. With this method, we apply the criterion to maximize efficiencies; establish lower and upper bounds, corresponding to the efficiencies of Curzon-Ahlborn-like and Carnot-like heat engines; and, finally, find analytical or numerical expressions for the efficiencies etame and etamax. etamax is the maximum irreversible efficiency; etame is the efficiency in which the irreversible efficiency achieves its maximum, in a similar way to the Curzon-Ahlborn efficiency (maximum work or power). The method was applied to a Brayton cycle, presenting internal dissipations of the working fluid and irreversibilities due to the finite-rate heat transfer between the heat engine and its reservoirs. Also, we applied this method to a Carnot cycle including the irreversibilities of a finite-rate heat transfer between the heat engine and its reservoirs, heat leak between the reservoirs, and internal dissipations of the working fluid. The results obtained for the Brayton cycle are more general and useful than those in the relevant literature.

  19. Free radical inactivation of pepsin

    NASA Astrophysics Data System (ADS)

    Josimović, Lj; Ruvarac, I.; Janković, I.; Jovanović, S. V.

    1994-06-01

    Alkylperoxy radicals containing one, two or three chlorine atoms, CO -2, O 2 - were reacted with pepsin in aqueous solutions. It was found that only Cl 3COO and CO -2 inactive pepsin, attacking preferentially the disulfide bridge. Transient spectra obtained upon completion of the Cl 3COO + pepsin reaction at pH 5 indicate that 20% of initially produced Cl 3COO radicals oxidizes tryptophan residues, and 40% disulfide bridges. The inactivation induced by the Cl 3COO radical increases at lower pH, and the maximal inactivation, Gin = 5.8, was observed at pH 1.5. The inactivation of pepsin by CO -2 radicals depends on the absorbed dose. The maximal inactivation, Gin = 4.5, was determined in the dose range from 38 to 53 Gy.

  20. CHLORINE INACTIVATION OF BACILLUS ENDOSPORES

    EPA Science Inventory

    The possibility of a bioterrorism event resulting in the release of Bacillus anthracis endospores into a drinking water distribution system necessitates research into means by which these endospores can be inactivated. This study was designed to determine the chlorine resistance...

  1. Influenza Vaccine, Inactivated or Recombinant

    MedlinePlus

    ... die from flu, and many more are hospitalized.Flu vaccine can:keep you from getting flu, make flu ... inactivated or recombinant influenza vaccine?A dose of flu vaccine is recommended every flu season. Children 6 months ...

  2. 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase.

    PubMed

    Alston, T A; Mela, L; Bright, H J

    1977-09-01

    We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] as follows. (i) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O(2) consumption decreases exponentially to a zero value. This pattern is duplicated by subsequent additions of mitochondria. The dependence of the apparent first-order rate constant for enzyme inhibition, as well as the number of enzyme turnovers completed before inhibition, on the concentrations of 3-nitropropionate carbanion and succinate are those expected for an active site-directed and irreversible inhibitor. (ii) The inactivated enzyme is not resuscitated by centrifugation and washing of the mitochondria, in contrast to malonate-treated enzyme, and malonate protects against irreversible, inhibition. (iii) The inhibitor species is 3-nitropropionate carbanion and no external nucleophile is required for inhibition. (iv) The respiratory rates, respiratory control ratios, and ADP/O ratios obtained with NAD-linked substrates are unaffected by 3-nitropropionate carbanion. These results show that 3-nitropropionate carbanion is a highly specific, time-dependent, and irreversible inhibitor of succinate dehydrogenase. By analogy with the reaction of nitroethane with D-amino acid oxidase, the data are consistent with the hypothesis that the carbanionic inhibitor forms a covalent N-5 adduct with the active site flavin. However, the precise mechanism of inactivation, as well as mechanistic extrapolations to the oxidation of succinate, must await the elucidation of the structure of the modified enzyme. We can now explain the toxicity of plants such as Indigofera endecaphylla for mammals and fowl as being due to the irreversible blockage of the Krebs cycle by 3-nitropropionate carbanion.

  3. 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase

    PubMed Central

    Alston, Theodore A.; Mela, Leena; Bright, Harold J.

    1977-01-01

    We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] as follows. (i) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O2 consumption decreases exponentially to a zero value. This pattern is duplicated by subsequent additions of mitochondria. The dependence of the apparent first-order rate constant for enzyme inhibition, as well as the number of enzyme turnovers completed before inhibition, on the concentrations of 3-nitropropionate carbanion and succinate are those expected for an active site-directed and irreversible inhibitor. (ii) The inactivated enzyme is not resuscitated by centrifugation and washing of the mitochondria, in contrast to malonate-treated enzyme, and malonate protects against irreversible, inhibition. (iii) The inhibitor species is 3-nitropropionate carbanion and no external nucleophile is required for inhibition. (iv) The respiratory rates, respiratory control ratios, and ADP/O ratios obtained with NAD-linked substrates are unaffected by 3-nitropropionate carbanion. These results show that 3-nitropropionate carbanion is a highly specific, time-dependent, and irreversible inhibitor of succinate dehydrogenase. By analogy with the reaction of nitroethane with D-amino acid oxidase, the data are consistent with the hypothesis that the carbanionic inhibitor forms a covalent N-5 adduct with the active site flavin. However, the precise mechanism of inactivation, as well as mechanistic extrapolations to the oxidation of succinate, must await the elucidation of the structure of the modified enzyme. We can now explain the toxicity of plants such as Indigofera endecaphylla for mammals and fowl as being due to the irreversible blockage of the Krebs cycle by 3-nitropropionate carbanion. PMID:269430

  4. Inhibition of Retinoblastoma Protein Inactivation

    DTIC Science & Technology

    2015-09-01

    intracellular growth signals to the cell cycle machinery that drives cell division . Inactivation of Rb pathway function is found in most human cancers...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The objective of this project is to discover and characterize molecules that inhibit breast cancer cell ...proliferation by maintaining activity of the retinoblastoma protein (Rb). Rb is inactivated to drive proliferation in normal and cancer cells by

  5. Slow inactivation in human cardiac sodium channels.

    PubMed Central

    Richmond, J E; Featherstone, D E; Hartmann, H A; Ruben, P C

    1998-01-01

    The available pool of sodium channels, and thus cell excitability, is regulated by both fast and slow inactivation. In cardiac tissue, the requirement for sustained firing of long-duration action potentials suggests that slow inactivation in cardiac sodium channels may differ from slow inactivation in skeletal muscle sodium channels. To test this hypothesis, we used the macropatch technique to characterize slow inactivation in human cardiac sodium channels heterologously expressed in Xenopus oocytes. Slow inactivation was isolated from fast inactivation kinetically (by selectively recovering channels from fast inactivation before measurement of slow inactivation) and structurally (by modification of fast inactivation by mutation of IFM1488QQQ). Time constants of slow inactivation in cardiac sodium channels were larger than previously reported for skeletal muscle sodium channels. In addition, steady-state slow inactivation was only 40% complete in cardiac sodium channels, compared to 80% in skeletal muscle channels. These results suggest that cardiac sodium channel slow inactivation is adapted for the sustained depolarizations found in normally functioning cardiac tissue. Complete slow inactivation in the fast inactivation modified IFM1488QQQ cardiac channel mutant suggests that this impairment of slow inactivation may result from an interaction between fast and slow inactivation. PMID:9635748

  6. Mitochondrial aconitase reaction with nitric oxide, S-nitrosoglutathione, and peroxynitrite: mechanisms and relative contributions to aconitase inactivation.

    PubMed

    Tórtora, Verónica; Quijano, Celia; Freeman, Bruce; Radi, Rafael; Castro, Laura

    2007-04-01

    Using highly purified recombinant mitochondrial aconitase, we determined the kinetics and mechanisms of inactivation mediated by nitric oxide (*NO), nitrosoglutathione (GSNO), and peroxynitrite (ONOO(-)). High *NO concentrations are required to inhibit resting aconitase. Brief *NO exposures led to a reversible inhibition competitive with isocitrate (K(I)=35 microM). Subsequently, an irreversible inactivation (0.65 M(-1) s(-1)) was observed. Irreversible inactivation was mediated by GSNO also, both in the absence and in the presence of substrates (0.23 M(-1) s(-1)). Peroxynitrite reacted with the [4Fe-4S] cluster, yielding the inactive [3Fe-4S] enzyme (1.1 x 10(5) M(-1) s(-1)). Carbon dioxide enhanced ONOO(-)-dependent inactivation via reaction of CO(3)*(-) with the [4Fe-4S] cluster (3 x 10(8) M(-1) s(-1)). Peroxynitrite also induced m-aconitase tyrosine nitration but this reaction did not contribute to enzyme inactivation. Computational modeling of aconitase inactivation by O(2)*(-) and *NO revealed that, when NO is produced and readily consumed, measuring the amount of active aconitase remains a sensitive method to detect variations in O(2)*(-) production in cells but, when cells are exposed to high concentrations of NO, aconitase inactivation does not exclusively reflect changes in rates of O(2)*(-) production. In the latter case, extents of aconitase inactivation reflect the formation of secondary reactive species, specifically ONOO(-) and CO(3)*(-), which also mediate m-aconitase tyrosine nitration, a footprint of reactive *NO-derived species.

  7. Irreversible fouling during multicycle microfiltration of wastewater effluent.

    PubMed

    Shan, Huifeng; Neufeld, Ronald D

    2007-12-01

    This study focused on irreversible fouling during microfiltration of primary and secondary effluents from municipal wastewater treatment plants. Flow resistances were calculated from the sum of clean membrane resistances, resultant cake layer resistances, and consequent irreversible fouling resistances. Results from a dead-end cell experimental system showed that the accumulated cake resistance was dominating for microfiltration of primary/secondary effluents. Suspended solids in the primary and secondary effluents had a similar compressibility index, n, with a value of approximately 0.5, indicating that they were moderately compressible particles. The value of irreversible resistance is dependent on the intensity of membrane cleaning; however, for a given membrane cleaning strategy, this value steadily increased and reached a maximum after approximately 6 cycles of filtration and cleaning. This study provided an explanation for the significant drop of throughput flux in the early application of membrane processes, and a plateau flux approached correspondingly.

  8. Irreversibility analysis in the process of solar distillation

    NASA Astrophysics Data System (ADS)

    Chávez, S.; Terres, H.; Lizardi, A.; López, R.; Lara, A.

    2017-01-01

    In this work an irreversibility analysis for the thermal process of solar distillation of three different substances is presented, for which it employs a solar still of a slope where three experimental tests with 5.5 L of brine, river water and MgCl2 were performed. Temperature data principally in the glass cover, absorber plate, fluid, environment and the incident solar radiation on the device were obtained. With measurements of temperature, solar radiation and exergetic balance, irreversibilities are found on the device. The results show that the highest values of irreversibilities are concentrated in the absorber plate with an average of 321 W, 342 W and 276 W, followed by the cover glass with an average of 75.8 W, 80.4 W and 86.7 W and finally the fluid with 15.3 W, 15.9 W and 16 W, for 5.5 L of brine, river water and MgCl2.

  9. Oxidative inactivation of paraoxonase1, an antioxidant protein and its effect on antioxidant action.

    PubMed

    Nguyen, Su Duy; Sok, Dai-Eun

    2003-12-01

    Paraoxonase1 (PON1), one of antioxidant proteins to protect low density lipoprotein (LDL) from the oxidation, is known to lose its activity in the oxidative environment. Here, we attempted to elucidate the possible mechanisms for the oxidative inactivation of PON1, and to examine the capability of hydroxyl radicals-inactivated PON1 to prevent against LDL oxidation. Of various oxidative systems, the ascorbate/Cu2+ system was the most potent in inactivating the purified PON1 (PON1) as well as HDL-bound PON1 (HDL-PON1). In contrast to a limited inactivation by Fe2+ (2.0 microM), the inclusion of Cu2+ (0.1-1.0 microM) remarkably enhanced the inactivation of PON1 in the presence of ascorbate (0.5mM). A similar result was also obtained with the inactivation of HDL-PON1. The inactivation of PON1 by ascorbate/Cu2+ was pevented by catalase, but not general hydroxyl radical scavengers, supporting inactivation. In addition, Cu2+ alone inactivated PON1, either soluble or HDL-bound, by different mechanisms, concentration-dependent. Separately, there was a reverse relationship between the inactivation of PON1 and its preventive action against LDL oxidation during Cu2+-induced oxidation of LDL. Noteworthy, ascorbate/Cu2+-inactivated PON1, which was charaterized by the partial loss of histidine residues, expressed a lower protection against Cu2+-induced LDL oxidation, compared to native PON1. Based on these results, it is proposed that metal-catalyzed oxidation may be a primary factor to cause the decrease of HDL-associated PON1 activity under oxidative stress, and radicals-induced inactivation of PON1 may lead to the decrease in its antioxidant action against LDL oxidation.

  10. Mechanism-based inhibitors for the inactivation of the bacterial phosphotriesterase.

    PubMed

    Hong, S B; Mullins, L S; Shim, H; Raushel, F M

    1997-07-22

    1-Bromovinyl (I), Z-2-bromovinyl (II), 1,2-dibromoethyl (III), and a series of 4-(halomethyl)-2-nitrophenyl (IVa-c) diethyl phosphate esters were examined as substrates and mechanism-based inhibitors for the bacterial phosphotriesterase. All of these compounds were found to act as substrates for the enzyme. Inhibitor I rapidly inactivated the enzyme within 1 min, giving a partition ratio of 230. The newly formed covalent adduct with inhibitor I was susceptible to hydrolysis at elevated values of pH and dissociation by NH2OH. Azide was not able to protect the enzyme from inactivation with inhibitor I, implying that the reactive species was not released into solution prior to the inactivation event. The reactive species was proposed to be either an acyl bromide or a ketene intermediate formed by the enzymatic hydrolysis of inhibitor I. Compounds II and III were shown to be relatively poor substrates of phosphotriesterase and they did not induce any significant inactivation of the enzyme. The inhibitor, 4-(bromomethyl)-2-nitrophenyl diethyl phosphate (IVa), was found to irreversibly inactivate the enzyme with a KI = 7.9 mM and kinact = 1. 2 min-1 at pH 9.0. There was no effect on the rate of inactivation upon the addition of the exogenous nucleophiles, azide, and NH2OH. The species responsible for the covalent modification of the enzyme by IVa was most likely a quinone methide formed by the elimination of bromide from the phenolic intermediate. NMR experiments demonstrated that the quinone methide did not accumulate in solution. The chloro (IVb) and fluoro (IVc) analogues did not inactivate the enzyme. These results suggest that the elimination of the halide ion from the phenolic intermediate largely determines the partition ratio for inactivation.

  11. Inactivation of urease by catechol: Kinetics and structure.

    PubMed

    Mazzei, Luca; Cianci, Michele; Musiani, Francesco; Lente, Gábor; Palombo, Marta; Ciurli, Stefano

    2017-01-01

    Urease is a Ni(II)-containing enzyme that catalyzes the hydrolysis of urea to yield ammonia and carbamate at a rate 10(15) times higher than the uncatalyzed reaction. Urease is a virulence factor of several human pathogens, in addition to decreasing the efficiency of soil organic nitrogen fertilization. Therefore, efficient urease inhibitors are actively sought. In this study, we describe a molecular characterization of the interaction between urease from Sporosarcina pasteurii (SPU) and Canavalia ensiformis (jack bean, JBU) with catechol, a model polyphenol. In particular, catechol irreversibly inactivates both SPU and JBU with a complex radical-based autocatalytic multistep mechanism. The crystal structure of the SPU-catechol complex, determined at 1.50Å resolution, reveals the structural details of the enzyme inhibition.

  12. Irreversible electroporation: evolution of a laboratory technique in interventional oncology.

    PubMed

    Deipolyi, Amy R; Golberg, Alexander; Yarmush, Martin L; Arellano, Ronald S; Oklu, Rahmi

    2014-01-01

    Electroporation involves applying electric field pulses to cells, leading to the alteration or destruction of cell membranes. Irreversible electroporation (IRE) creates permanent defects in cell membranes and induces cell death. By directly targeting IRE to tumors, percutaneous nonthermal ablation is possible. The history of IRE, evolution of concepts, theory, biological applications, and clinical data regarding its safety and efficacy are discussed.

  13. Irreversible electroporation: evolution of a laboratory technique in interventional oncology

    PubMed Central

    Deipolyi, Amy R.; Golberg, Alexander; Yarmush, Martin L.; Arellano, Ronald S.; Oklu, Rahmi

    2014-01-01

    Electroporation involves applying electric field pulses to cells, leading to the alteration or destruction of cell membranes. Irreversible electroporation (IRE) creates permanent defects in cell membranes and induces cell death. By directly targeting IRE to tumors, percutaneous nonthermal ablation is possible. The history of IRE, evolution of concepts, theory, biological applications, and clinical data regarding its safety and efficacy are discussed. PMID:24412820

  14. When an Adiabatic Irreversible Expansion or Compression Becomes Reversible

    ERIC Educational Resources Information Center

    Anacleto, Joaquim; Ferreira, J. M.; Soares, A. A.

    2009-01-01

    This paper aims to contribute to a better understanding of the concepts of a "reversible process" and "entropy". For this purpose, an adiabatic irreversible expansion or compression is analysed, by considering that an ideal gas is expanded (compressed), from an initial pressure P[subscript i] to a final pressure P[subscript f], by being placed in…

  15. Reactivation strategies by unfolding/refolding of chymotrypsin derivatives after inactivation by organic solvents.

    PubMed

    Soler, G; Bastida, A; Blanco, R M; Fernández-Lafuente, R; Guisán, J M

    1997-04-25

    Immobilized enzyme derivatives, in organic media at neutral pH and moderate temperatures, should be mainly and perhaps uniquely inactivated by promotion of conformational changes on their 3D structure. Subsequent irreversible inactivation mechanisms (intermolecular aggregations, chemical modifications, thiol-disulfide exchanges) are thus impossible. However, simple reincubation in aqueous medium of enzymes previously inactivated by solvents usually yields significant but slow and incomplete reactivations. Disruption of incorrect protein structures by denaturing agents (urea, guanidine) is proposed as a new strategy to get rapid, complete and technologically feasible reactivations. By using multipoint immobilized chymotrypsin derivatives, we have evaluated the possibility of unfolding and further refolding of native (non-inactivated) derivatives by different denaturing conditions. After unfolding in 8 M guanidine, derivatives were quickly and completely refolded up to 100% of catalytic activity in 10 minutes. Besides, successive cycles of unfolding and refolding could be exactly reproduced. Finally we checked the possibility to reactivate chymotrypsin derivatives inactivated by dioxane. Simple reincubations in aqueous media yielded a poor reactivation even after 24 hours. However, unfolding in 8 M guanidine enabled complete reactivation in less than 2 hours. From this point of view, by working under 'chemically inert conditions' (moderate pH and temperatures), fully dispersed covalently immobilized enzyme derivatives seem to behave as almost everlasting catalysts despite the very deleterious effect of organic media.

  16. Inactivated smallpox vaccine. A comparison of inactivation methods

    PubMed Central

    Turner, G. S.; Squires, E. J.; Murray, H. G. S.

    1970-01-01

    Vaccines were prepared from a single pool of high-titred vaccinia virus and inactivated by six methods, namely heat, formalin, hydroxylamine, β-propiolactone, ultraviolet irradiation, and visible light and methylene blue. Large doses of the vaccines were required to protect mice against intracerebral challenge. Differences in protection were not attributable to the method of their inactivation. The vaccines also induced similar degrees of skin immunity in rabbits which showed no severe dermal reactions when challenged with either homologous killed vaccine or live virus. The virus-neutralizing, haemagglutinin-inhibiting and complement fixing antibody responses to the vaccines differed; heat-inactivation preserved these antigens least well and β-propiolactone apparently the best. In both rabbits and mice there was little association between the different antibody responses to each vaccine or between the degrees of antibody response and the protection they induced. The relation of these findings to pox-virus immunity and the use of inactivated smallpox vaccine in man is discussed. PMID:4988047

  17. The intrinsically disordered domain of the antitoxin Phd chaperones the toxin Doc against irreversible inactivation and misfolding.

    PubMed

    De Gieter, Steven; Konijnenberg, Albert; Talavera, Ariel; Butterer, Annika; Haesaerts, Sarah; De Greve, Henri; Sobott, Frank; Loris, Remy; Garcia-Pino, Abel

    2014-12-05

    The toxin Doc from the phd/doc toxin-antitoxin module targets the cellular translation machinery and is inhibited by its antitoxin partner Phd. Here we show that Phd also functions as a chaperone, keeping Doc in an active, correctly folded conformation. In the absence of Phd, Doc exists in a relatively expanded state that is prone to dimerization through domain swapping with its active site loop acting as hinge region. The domain-swapped dimer is not capable of arresting protein synthesis in vitro, whereas the Doc monomer is. Upon binding to Phd, Doc becomes more compact and is secured in its monomeric state with a neutralized active site.

  18. Indomethacin inactivates gastric peroxidase to induce reactive-oxygen-mediated gastric mucosal injury and curcumin protects it by preventing peroxidase inactivation and scavenging reactive oxygen.

    PubMed

    Chattopadhyay, Ishita; Bandyopadhyay, Uday; Biswas, Kaushik; Maity, Pallab; Banerjee, Ranajit K

    2006-04-15

    We have investigated the mechanism of indomethacin-induced gastric ulcer caused by reactive oxygen species (ROS) and the gastroprotective effect of curcumin thereon. Curcumin dose-dependently blocks indomethacin-induced gastric lesions, showing 82% protection at 25 mg/kg. Indomethacin-induced oxidative damage by ROS as shown by increased lipid peroxidation and thiol depletion is almost completely blocked by curcumin. Indomethacin causes nearly fivefold increase in hydroxyl radical (()OH) and significant inactivation of gastric mucosal peroxidase to elevate endogenous H(2)O(2) and H(2)O(2)-derived ()OH, which is prevented by curcumin. In vitro studies indicate that indomethacin inactivates peroxidase irreversibly only in presence of H(2)O(2) by acting as a suicidal substrate. 5,5-Dimethyl-pyrroline-N-oxide (DMPO) protects the peroxidase, indicating involvement of indomethacin radical in the inactivation. Indomethacin radical was also detected in the peroxidase-indomethacin-H(2)O(2) system as DMPO adduct (a(N) = 15 G, a(beta)(H) = 16 G) by electron spin resonance spectroscopy. Curcumin protects the peroxidase in a concentration-dependent manner and consumes H(2)O(2) for its oxidation as a suitable substrate of the peroxidase, thereby blocking indomethacin oxidation. Curcumin can also scavenge ()OH in vitro. We suggest that curcumin protects gastric damage by efficient removal of H(2)O(2) and H(2)O(2) -derived ()OH by preventing peroxidase inactivation by indomethacin.

  19. Kinetic and structural characterization of caspase-3 and caspase-8 inhibition by a novel class of irreversible inhibitors

    SciTech Connect

    Wang, Zhigang; Watt, William; Brooks, Nathan A.; Harris, Melissa S.; Urban, Jan; Boatman, Douglas; McMillan, Michael; Kahn, Michael; Heinrikson, Robert L.; Finzel, Barry C.; Wittwer, Arthur J.; Blinn, James; Kamtekar, Satwik; Tomasselli, Alfredo G.

    2010-09-17

    Because of their central role in programmed cell death, the caspases are attractive targets for developing new therapeutics against cancer and autoimmunity, myocardial infarction and ischemic damage, and neurodegenerative diseases. We chose to target caspase-3, an executioner caspase, and caspase-8, an initiator caspase, based on the vast amount of information linking their functions to diseases. Through a structure-based drug design approach, a number of novel {beta}-strand peptidomimetic compounds were synthesized. Kinetic studies of caspase-3 and caspase-8 inhibition were carried out with these urazole ring-containing irreversible peptidomimetics and a known irreversible caspase inhibitor, Z-VAD-fmk. Using a stopped-flow fluorescence assay, we were able to determine individual kinetic parameters of caspase-3 and caspase-8 inhibition by these inhibitors. Z-VAD-fmk and the peptidomimetic inhibitors inhibit caspase-3 and caspase-8 via a three-step kinetic mechanism. Inhibition of both caspase-3 and caspase-8 by Z-VAD-fmk and of caspase-3 by the peptidomimetic inhibitors proceeds via two rapid equilibrium steps followed by a relatively fast inactivation step. However, caspase-8 inhibition by the peptidomimetics goes through a rapid equilibrium step, a slow-binding reversible step, and an extremely slow inactivation step. The crystal structures of inhibitor complexes of caspases-3 and -8 validate the design of the inhibitors by illustrating in detail how they mimic peptide substrates. One of the caspase-8 structures also shows binding at a secondary, allosteric site, providing a possible route to the development of noncovalent small molecule modulators of caspase activity.

  20. A dielectric barrier discharge terminally inactivates RNase A by oxidizing sulfur-containing amino acids and breaking structural disulfide bonds

    NASA Astrophysics Data System (ADS)

    Lackmann, J.-W.; Baldus, S.; Steinborn, E.; Edengeiser, E.; Kogelheide, F.; Langklotz, S.; Schneider, S.; Leichert, L. I. O.; Benedikt, J.; Awakowicz, P.; Bandow, J. E.

    2015-12-01

    RNases are among the most stable proteins in nature. They even refold spontaneously after heat inactivation, regaining full activity. Due to their stability and universal presence, they often pose a problem when experimenting with RNA. We investigated the capabilities of nonthermal atmospheric-pressure plasmas to inactivate RNase A and studied the inactivation mechanism on a molecular level. While prolonged heating above 90 °C is required for heat inactivating RNase A, direct plasma treatment with a dielectric barrier discharge (DBD) source caused permanent inactivation within minutes. Circular dichroism spectroscopy showed that DBD-treated RNase A unfolds rapidly. Raman spectroscopy indicated methionine modifications and formation of sulfonic acid. A mass spectrometry-based analysis of the protein modifications that occur during plasma treatment over time revealed that methionine sulfoxide formation coincides with protein inactivation. Chemical reduction of methionine sulfoxides partially restored RNase A activity confirming that sulfoxidation is causal and sufficient for RNase A inactivation. Continued plasma exposure led to over-oxidation of structural disulfide bonds. Using antibodies, disulfide bond over-oxidation was shown to be a general protein inactivation mechanism of the DBD. The antibody’s heavy and light chains linked by disulfide bonds dissociated after plasma exposure. Based on their ability to inactivate proteins by oxidation of sulfur-containing amino acids and over-oxidation of disulfide bonds, DBD devices present a viable option for inactivating undesired or hazardous proteins on heat or solvent-sensitive surfaces.

  1. BNNT-mediated irreversible electroporatio: its potential on cancer cells

    SciTech Connect

    Vittoria Raffa, Cristina Riggio, Michael W. Smith, Kevin C. Jordan, Wei Cao, Alfred Cuschieri

    2012-10-01

    Tissue ablation, i.e., the destruction of undesirable tissues, has become an important minimally invasive technique alternative to resection surgery for the treatment of tumours. Several methods for tissue ablation are based on thermal techniques using cold, e.g. cryosurgery [1] or heat, e.g. radiofrequency [2] or high-intensity focused ultrasound [3] or nanoparticle-mediated irradiation [4]. Alternatively, irreversible electroporation (IRE) has been proposed as non thermal technique for minimally invasive tissue ablation based on the use of electrical pulses. When the electric field is applied to a cell, a change in transmembrane potential is induced, which can cause biochemical and physiological changes of the cell. When the threshold value of the transmembrane potential is exceeded, the cell membrane becomes permeable, thus allowing entrance of molecules that otherwise cannot cross the membrane [5]. A further increase in the electric field intensity may cause irreversible membrane permeabilization and cell death. These pulses create irreversible defects (pores) in the cell membrane lipid bilayer, causing cell death through loss of cell homeostasis [6]. This is desirable in tumour ablation in order to produce large cell death, without the use of cytostatic drugs. A study of Davalos, Mir and Rubinsky showed that IRE can ablate substantial volumes of tissue without inducing a thermal effect and therefore serve as an independent and new tissue ablation modality; this opened the way to the use of IRE in surgery [7]. Their finding was subsequently confirmed in studies on cells [8], small animal models [9] and in large animal models in the liver [10] and the heart [11]. The most important finding in these papers is that irreversible electroporation produces precisely delineated ablation zones with cell scale resolution between ablated and non-ablated areas, without zones in which the extent of damage changes gradually as during thermal ablation. Furthermore, it is

  2. Heat inactivation of enteric viruses in dewatered wastewater sludge.

    PubMed

    Ward, R L; Ashley, C S

    1978-12-01

    The effect of moisture content on the rates of heat inactivation of enteric viruses in wastewater sludge was determined. The protective effect of raw sludge on poliovirus previously observed (R. L. Ward, C. S. Ashley, and R. H. Moseley, Appl. Environ. Microbiol. 32:339--346, 1976) was found to be greatly enhanced in sludge dewatered by evaporation. Other enteroviruses responded in a similar fashion. This effect did not appear to be due merely to the state of dryness of the sludge samples because in humus-deficient soil, a relatively inert material, the rate of poliovirus inactivation by heat was not significantly altered through dewatering. Instead, this effect appeared to have been caused by protective substances in the sludge, such as detergents, which are concentrated through dewatering. As reported previously (R. L. Ward and C. S. Ashley, Appl. Environ. Microbiol. 34:681-688, 1977; R. L. Ward and C. S. Ashley, Appl. Environ. Microbiol 36:889--897, 1978) raw sludge is not protective of reovirus, but, instead, the ionic detergents in sludge cause the rate of heat inactivation of this virus to be accelerated. Dewatering of sludge, however, was found to partially reverse this virucidal effect. Evidence is presented indicating that this reversal is caused by an unidentified protective substance in sludge also concentrated through dewatering. Finally, it was shown that the effects of raw sludge on heat inactivation of poliovirus and reovirus are greatly reduced by composting, a result that correlated with the degradation of detergents.

  3. Determination of Time Dependent Virus Inactivation Rates

    NASA Astrophysics Data System (ADS)

    Chrysikopoulos, C. V.; Vogler, E. T.

    2003-12-01

    A methodology is developed for estimating temporally variable virus inactivation rate coefficients from experimental virus inactivation data. The methodology consists of a technique for slope estimation of normalized virus inactivation data in conjunction with a resampling parameter estimation procedure. The slope estimation technique is based on a relatively flexible geostatistical method known as universal kriging. Drift coefficients are obtained by nonlinear fitting of bootstrap samples and the corresponding confidence intervals are obtained by bootstrap percentiles. The proposed methodology yields more accurate time dependent virus inactivation rate coefficients than those estimated by fitting virus inactivation data to a first-order inactivation model. The methodology is successfully applied to a set of poliovirus batch inactivation data. Furthermore, the importance of accurate inactivation rate coefficient determination on virus transport in water saturated porous media is demonstrated with model simulations.

  4. INACTIVATION OF CRYPTOSPORIDIUM PARVUM OOCYSTS WITH OZONE

    EPA Science Inventory

    Ozone inactivation rates for Cryptosporidium parvum (C. parvum) oocysts were determined with an in-vitro excystation method based on excysted sporozoite counts. Results were consistent with published animal infectivity data for the same C. parvum strain. The inactivation kinetics...

  5. CRYPTOSPORIDIUM LOG INACTIVATION CALCULATION METHODS

    EPA Science Inventory

    Appendix O of the Surface Water Treatment Rule (SWTR) Guidance Manual introduces the CeffT10 (i.e., reaction zone outlet C value and T10 time) method for calculating ozone CT value and Giardia and virus log inactivation. The LT2ESWTR Pre-proposal Draft Regulatory Language for St...

  6. Overcoming of energy barrier for irreversible magnetization in nanocomposite magnets

    NASA Astrophysics Data System (ADS)

    Li, Zhu-bai; Zhang, Ying; Shen, Bao-gen; Zhang, Ming; Hu, Feng-xia; Sun, Ji-rong

    2017-01-01

    The irreversible magnetization occurs mainly in hard grains in nanocomposite magnets, and the domain wall involves a little part of defect region in irreversible magnetization due to the self-interaction. The investigation on thermal activation shows that the defect region involved in domain wall becomes narrower due to the TiNb addition in Pr2Fe14B/α-Fe magnets. The defect region augments the energy density in the negative direction of domain wall to overcome the energy barrier of perfect hard region. The soft phase, exchange-coupled with defect region at hard grain outer-layer, promotes magnetization reversal in defect region by exchange coupling. While the defect region plays a role as a ladder to overcome the energy barrier, resulting in the decrease of coecivity more or less depending upon the width and anisotropy of defect region.

  7. Reversible and irreversible interactions between elastin and plasma lipoproteins.

    PubMed

    Winlove, C P; Parker, K H; Ewins, A R

    1985-03-08

    The interactions between radiolabeled, human plasma lipoproteins and elastin derived from bovine ligamentum nuchae were investigated using a washout technique. The interaction was characterised by Ki, a coefficient of irreversible binding, and Kr, the reversible partition coefficient. For both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) the Ki values decreased as total lipoprotein concentration increased, suggesting that the binding is saturable, and were similar in magnitude to those measured by other workers using elastin derived from the human aorta. For both LDL and HDL the Kr values were independent of lipoprotein concentration in the range 0.1 microgram/ml-1.5 micrograms/ml. At a total protein concentration of 1.5 mg/ml in the incubation medium, the reversible interactions were comparable in magnitude to the irreversible.

  8. Irreversible sortase A-mediated ligation driven by diketopiperazine formation.

    PubMed

    Liu, Fa; Luo, Ethan Y; Flora, David B; Mezo, Adam R

    2014-01-17

    Sortase A (SrtA)-mediated ligation has emerged as an attractive tool in bioorganic chemistry attributing to the remarkable specificity of the ligation reaction and the physiological reaction conditions. However, the reversible nature of this reaction limits the efficiency of the ligation reaction and has become a significant constraint to its more widespread use. We report herein a novel set of SrtA substrates (LPETGG-isoacyl-Ser and LPETGG-isoacyl-Hse) that can be irreversibly ligated to N-terminal Gly-containing moieties via the deactivation of the SrtA-excised peptide fragment through diketopiperazine (DKP) formation. The convenience of the synthetic procedure and the stability of the substrates in the ligation buffer suggest that both LPETGG-isoacyl-Ser and LPETGG-isoacyl-Hse are valuable alternatives to existing irreversible SrtA substrate sequences.

  9. Irreversible adsorption of phenolic compounds by activated carbons

    SciTech Connect

    Grant, T.M.; King, C.J.

    1988-12-01

    Studies were undertaken to determine the reasons why phenolic sorbates can be difficult to remove and recover from activated carbons. The chemical properties of the sorbate and the adsorbent surface, and the influences of changes in the adsorption and desorption conditions were investigated. Comparison of isotherms established after different contact times or at different temperatures indicated that phenolic compounds react on carbon surfaces. The reaction rate is a strong function of temperature. Regeneration of carbons by leaching with acetone recovered at least as much phenol as did regeneration with other solvents or with displacers. The physiochemical properties of adsorbents influences irreversible uptakes. Sorbates differed markedly in their tendencies to undergo irreversible adsorption. 64 refs., 47 figs., 32 tabs.

  10. Prostaglandin E2 to diagnose between reversible and irreversible pulpitis.

    PubMed

    Petrini, M; Ferrante, M; Ciavarelli, L; Brunetti, L; Vacca, M; Spoto, G

    2012-01-01

    The aim of this work is to verify a correlation between the grade of inflammation and the concentration of PGE2 in human dental pulp. A total of 25 human dental pulps were examined by histological analysis and radioimmunologic dosage of PGE2. The pulps used in this experiment were from healthy and symptomatic teeth; the first ones were collected from teeth destined to be extracted for orthodontic reasons. An increase was observed of PGE2 in reversible pulpitis compared with healthy pulps and with the irreversible pulpitis and the clear decrease of these when NSAIDs are taken. This study demonstrates that PGE2 level is correlated to histological analysis thus allowing to distinguish symptomatic teeth in reversible and irreversible pulpitis.

  11. Flux pinning characteristics and irreversibility line in high temperature superconductors

    NASA Technical Reports Server (NTRS)

    Matsushita, T.; Ihara, N.; Kiuchi, M.

    1995-01-01

    The flux pinning properties in high temperature superconductors are strongly influenced by thermally activated flux motion. The scaling relation of the pinning force density and the irreversibility line in various high temperature superconductors are numerically analyzed in terms of the flux creep model. The effect of two factors, i.e., the flux pinning strength and the dimensionality of the material, on these properties are investigated. It is speculated that the irreversibility line in Bi-2212 superconductors is one order of magnitude smaller than that in Y-123, even if the flux pinning strength in Bi-2212 is improved up to the level of Y-123. It is concluded that these two factors are equally important in determination of the flux pinning characteristics at high temperatures.

  12. Aftereffect in rocks caused by preexisting irreversible deformations

    SciTech Connect

    Stavrogin, A.N.; Shirkes, O.A.

    1987-05-01

    In this paper, rock specimens cut as cores of a diameter of 30 mm, 80 mm in length, were subjected to irreversible deformation in a high hydrostatic pressure chamber according to Karman's procedure. The types of rocks investigated were white Koelga marble, non-burst-hazardous (NBH) sandstone from Donets Basin, limestone from Estonslanets deposit and brown coal from Shurab coal deposit. Marble specimens were subjected to the most extensive studies. The aftereffect curves are shown for each type of rock studied. Aftereffect deformations of rocks are basically creep flows occurring under the effect of residual stresses introduced into the rock material on the course of its irreversible deformation by a high hydrostatic pressure, according to the authors. The physical nature of the residual stresses in the rocks and the mechanism of their creation are examined at the level of structural elements (grains or crystals).

  13. Irreversibility and chaos: role of lubrication interactions in sheared suspensions.

    PubMed

    Metzger, Bloen; Pham, Phong; Butler, Jason E

    2013-05-01

    We investigate non-Brownian particles suspended in a periodic shear-flow using simulations. Following Metzger and Butler [Phys. Rev. E 82, 051406 (2010)], we show that the chaotic dynamics arising from lubrication interactions are too weak to generate an observable particle dispersion. The irreversibility observed in periodic flow is dominated by contact interactions. Nonetheless, we show that lubrication interactions must be included in the calculation to obtain results that agree with experiments.

  14. Variability of Irreversible Poleward Transport in the Lower Stratosphere

    NASA Technical Reports Server (NTRS)

    Olsen, Mark; Douglass, Anne; Newman, Paul; Nash, Eric; Witte, Jacquelyn; Ziemke, Jerry

    2011-01-01

    The ascent and descent of the Brewer-Dobson circulation plays a large role in determining the distributions of many constituents in the extratropical lower stratosphere. However, relatively fast, quasi-horizontal transport out of the tropics and polar regions also significantly contribute to determining these distributions. The tropical tape recorder signal assures that there must be outflow from the tropics into the extratropical lower stratosphere. The phase of the quasi-biennial oscillation (QBO) and state of the polar vortex are known to modulate the transport from the tropical and polar regions, respectively. In this study we examine multiple years of ozone distributions in the extratropical lower stratosphere observed by the Aura Microwave Limb Sounder (MLS) and the Aura High Resolution Dynamic Limb Sounder (HIRDLS). The distributions are compared with analyses of irreversible, meridional isentropic transport. We show that there is considerable year-to-year seasonal variability in the amount of irreversible transport from the tropics, which is related to both the phase of the QBO and the state of the polar vortex. The reversibility of the transport is consistent with the number of observed breaking waves. The variability of the atmospheric index of refraction in the lower stratosphere is shown to be significantly correlated with the wave breaking and amount of irreversible transport. Finally, we will show that the seasonal extratropical stratosphere to troposphere transport of ozone can be substantially modulated by the amount of irreversible meridional transport in the lower stratosphere and we investigate how observable these differences are in data of tropospheric ozone.

  15. The State of Irreversible Electroporation in Interventional Oncology

    PubMed Central

    Silk, Mikhail; Tahour, David; Srimathveeravalli, Govindarajan; Solomon, Stephen B.; Thornton, Raymond H.

    2014-01-01

    A new ablation modality, irreversible electroporation (IRE), has been of increasing interest in interventional radiology. Its nonthermal mechanism of action of killing tumor cells allows physicians the ability to ablate tumors in areas previously contraindicated for thermal ablation. This article reviews the current published clinical outcomes, imaging follow-up, and the current knowledge gaps in the procedure for patients treated with IRE. PMID:25053862

  16. Entropy production and irreversibility of dissipative trajectories in electric circuits.

    PubMed

    Chiang, K-H; Lee, C-L; Lai, P-Y; Chen, Y-F

    2017-01-01

    We experimentally examine the equivalence between the entropy production evaluated from irreversibility of trajectories and the physical dissipation in dissipative processes via electric resistor-capacitor (RC) circuits. The examinations are performed for two nonequilibrium steady states that are driven by an injected current and temperature difference, respectively. Such an equivalence demonstrates a parameter-free method to evaluate the entropy production of a system. The effects of configurational and temporal resolutions are also studied.

  17. Spontaneous subtalar fusion: an irreversible complication of subtalar arthroereisis.

    PubMed

    Lui, Tun Hing

    2014-01-01

    Subtalar arthroereisis has been used for the treatment of symptomatic flexible flatfoot deformities in both pediatric and adult patients. Chronic sinus tarsi pain is the most common complication of this procedure and can be relieved by removal of the implant. We describe a case of spontaneous fusion of the subtalar joint after arthroereisis. This is an irreversible complication that should be described to the patient as a rare, but possible, outcome of arthroereisis of the subtalar joint.

  18. Anesthetic Efficacy in Irreversible Pulpitis: A Randomized Clinical Trial.

    PubMed

    Allegretti, Carlos E; Sampaio, Roberta M; Horliana, Anna C R T; Armonia, Paschoal L; Rocha, Rodney G; Tortamano, Isabel Peixoto

    2016-01-01

    Inferior alveolar nerve block has a high failure rate in the treatment of mandibular posterior teeth with irreversible pulpitis. The aim of this study was to compare the anesthetic efficacy of 4% articaine, 2% lidocaine and 2% mepivacaine, all in combination with 1:100,000 epinephrine, in patients with irreversible pulpitis of permanent mandibular molars during a pulpectomy procedure. Sixty-six volunteers from the Emergency Center of the School of Dentistry, University of São Paulo, randomly received 3.6 mL of local anesthetic as a conventional inferior alveolar nerve block (IANB). The subjective signal of lip numbness, pulpal anesthesia and absence of pain during the pulpectomy procedure were evaluated respectively, by questioning the patient, stimulation using an electric pulp tester and a verbal analogue scale. All patients reported the subjective signal of lip numbness. Regarding pulpal anesthesia success as measured with the pulp tester, the success rate was respectively 68.2% for mepivacaine, 63.6% for articaine and 63.6% for lidocaine. Regarding patients who reported no pain or mild pain during the pulpectomy, the success rate was, respectively 72.7% for mepivacaine, 63.6% for articaine and 54.5% for lidocaine. These differences were not statistically significant. Neither of the solutions resulted in 100% anesthetic success in patients with irreversible pulpitis of mandibular molars.

  19. Irreversible Electroporation for Focal Ablation at the Porta Hepatis

    SciTech Connect

    Kasivisvanathan, Veeru; Thapar, Ankur Oskrochi, Youssof; Picard, John; Leen, Edward L. S.

    2012-12-15

    Patients with chemotherapy-refractory liver metastases who are not candidates for surgery may be treated with focal ablation techniques with established survival benefits. Irreversible electroporation is the newest of these and has the putative advantages of a nonthermal action, preventing damage to adjacent biliary structures and bowel. This report describes the use of irreversible electroporation in a 61-year-old man with a solitary chemoresistant liver metastasis unsuitable for radiofrequency ablation as a result of its proximity to the porta hepatis. At 3 months, tumor size was decreased on computed tomography from 28 Multiplication-Sign 19 to 20 Multiplication-Sign 17 mm, representing stable disease according to the response evaluation criteria in solid tumors. This corresponded to a decrease in tumor volume size from 5.25 to 3.16 cm{sup 3}. There were no early or late complications. Chemoresistant liver metastases in the proximity of the porta hepatis that are considered to be too high a risk for conventional surgery or thermal ablation may be considered for treatment by the novel ablation technique of irreversible electroporation.

  20. Irreversibility in energy processes: Non-dimensional quantification and balance

    NASA Astrophysics Data System (ADS)

    Pons, Michel

    2004-06-01

    The concept of thermodynamic efficiency (ratio of real cycle efficiency by Carnot efficiency) is well-known. The concept of numbers of entropy-production and of exergy-loss proposed by A. Bejan are also known, but rarely used. The present study firstly evidences that these two last numbers are actually identical, thus being a common number of irreversibility, independent of the method used for obtaining it. The study also evidences a non-dimensional irreversibility balance that applies to any energy conversion process. This balance correlates the thermodynamic efficiency of a whole process (which in most cases equals the exergetic efficiency) and the numbers of irreversibility of the different components or sub-processes involved in this process. Moreover, the basic additivity of entropy-productions and exergy-losses is maintained in this balance. This balance applies to the basic cycles (heat-engines, refrigerators, heat-pumps and heat-transformers), either work- or heat-powered. It also applies to more complex cycles (heat-powered cycles consuming electricity, four-temperature heat-powered cycles, cogeneration processes), thus giving a robust framework for analyzing these cycles.

  1. Effective Chemical Inactivation of Ebola Virus

    PubMed Central

    Haddock, Elaine; Feldmann, Friederike

    2016-01-01

    Reliable inactivation of specimens before removal from high-level biocontainment is crucial for safe operation. To evaluate efficacy of methods of chemical inactivation, we compared in vitro and in vivo approaches using Ebola virus as a surrogate pathogen. Consequently, we have established parameters and protocols leading to reliable and effective inactivation. PMID:27070504

  2. Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States.

    PubMed

    Jo, Sooyeon; Bean, Bruce P

    2017-04-01

    Lacosamide is an antiseizure agent that targets voltage-dependent sodium channels. Previous experiments have suggested that lacosamide is unusual in binding selectively to the slow-inactivated state of sodium channels, in contrast to drugs like carbamazepine and phenytoin, which bind tightly to fast-inactivated states. Using heterologously expressed human Nav1.7 sodium channels, we examined the state-dependent effects of lacosamide. Lacosamide induced a reversible shift in the voltage dependence of fast inactivation studied with 100-millisecond prepulses, suggesting binding to fast-inactivated states. Using steady holding potentials, lacosamide block was very weak at -120 mV (3% inhibition by 100 µM lacosamide) but greatly enhanced at -80 mV (43% inhibition by 100 µM lacosamide), where there is partial fast inactivation but little or no slow inactivation. During long depolarizations, lacosamide slowly (over seconds) put channels into states that recovered availability slowly (hundreds of milliseconds) at -120 mV. This resembles enhancement of slow inactivation, but the effect was much more pronounced at -40 mV, where fast inactivation is complete, but slow inactivation is not, than at 0 mV, where slow inactivation is maximal, more consistent with slow binding to fast-inactivated states than selective binding to slow-inactivated states. Furthermore, inhibition by lacosamide was greatly reduced by pretreatment with 300 µM lidocaine or 300 µM carbamazepine, suggesting that lacosamide, lidocaine, and carbamazepine all bind to the same site. The results suggest that lacosamide binds to fast-inactivated states in a manner similar to other antiseizure agents but with slower kinetics of binding and unbinding.

  3. Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin.

    PubMed

    Ogino, Himari; Hisanaga, Arisa; Kohno, Takao; Kondo, Yuta; Okumura, Kyoko; Kamei, Takana; Sato, Tempei; Asahara, Hiroshi; Tsuiji, Hitomi; Fukata, Masaki; Hattori, Mitsuharu

    2017-03-22

    The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, noninvasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro, but it remains controversial as to whether this effect occurs in vivo Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons. This enzyme was identified as a disintegrin and metalloproteinase with thrombospondin motifs-3 (ADAMTS-3). Recombinant ADAMTS-3 cleaved Reelin at the N-t site. ADAMTS-3 was expressed in excitatory neurons in the cerebral cortex and hippocampus. N-t cleavage of Reelin was markedly decreased in the embryonic cerebral cortex of ADAMTS-3 knock-out (KO) mice. Importantly, the amount of Dab1 and the phosphorylation level of Tau, which inversely correlate with Reelin activity, were significantly decreased in the cerebral cortex of ADAMTS-3 KO mice. Conditional KO mice, in which ADAMTS-3 was deficient only in the excitatory neurons of the forebrain, showed increased dendritic branching and elongation in the postnatal cerebral cortex. Our study shows that ADAMTS-3 is the major enzyme that cleaves and inactivates Reelin in the cerebral cortex and hippocampus. Therefore, inhibition of ADAMTS-3 may be an effective treatment for neuropsychiatric and neurodegenerative disorders.SIGNIFICANCE STATEMENT ADAMTS-3 was identified as the protease that cleaves and inactivates Reelin in the cerebral cortex and hippocampus. ADAMTS-3 was expressed in the excitatory neurons of the embryonic and postnatal cerebral cortex and hippocampus. Cleavage by ADAMTS-3 is the major

  4. Submicromolar concentrations of zinc irreversibly reduce a calcium-dependent potassium current in rat hippocampal neurons in vitro.

    PubMed

    Sim, J A; Cherubini, E

    1990-01-01

    The action of the endogenous divalent cation zinc on Ca2+ and Ca2(+)-dependent currents was studied in rat hippocampal CA1 and CA3 neurons in vitro, by means of a single electrode voltage clamp technique. Bath application of zinc (0.5-1 microM) produced a small membrane depolarization associated with an increase in synaptic noise and cell excitability and a depression of the afterhyperpolarization following a train of action potentials. The effects on the afterhyperpolarization, could not be reversed on washout. In voltage-clamped neurons, zinc induced a steady inward current and reduced, at resting membrane potential, the peak amplitude of the outward current underlying the afterhyperpolarization, IAHP. In caesium loaded neurons (in the presence of tetrodotoxin and tetraethylammonium), zinc reduced the slow inactivating Ca2+ current activated from a holding potential of -40 mV. Similar results were observed with nickel and cobalt at comparable concentrations, with Zn2+ greater than Ni2+ greater than Co2+, in their order of potency. In contrast to nickel and cobalt the effects of zinc did not reverse on washout. These results suggest that low concentrations of zinc enhance cell excitability by reducing IAHP. In addition, zinc reduces the slow inactivating voltage-dependent Ca2+ current. The irreversible effect of this metal ion is compatible with a toxic, intracellular site of action.

  5. Interface-mediated inactivation of pancreatic lipase by a water-reactive compound: 2-sulfobenzoic cyclic anhydride.

    PubMed

    Moulin, A; Fourneron, J D; Piéroni, G; Verger, R

    1989-07-25

    2-Sulfobenzoic cyclic anhydride (SBA) rapidly and selectively inactivates porcine pancreatic lipase (PPL) only when added during the hydrolysis of an emulsified ester such as tributyrin or dodecyl acetate. The present data suggest that the inactivation of PPL occurs preferentially at the oil/water interface and not in the aqueous phase, since colipase and bile salt were found to adversely affect the inhibition process. Moreover, it is shown that at a molar ratio of SBA to pure PPL of 1, 40% of the lipase activity was already irreversibly lost. Complete inactivation was observed at SBA to pure PPL molar ratios of 120. A 60% inactivation occurred when 0.5 mol of 3H-labeled SBA was attached per mole of PPL. The SBA-inactivated PPL competes for binding to the dodecyl acetate/water interface as efficiently as the native enzyme. Larger SBA concentrations are required when crude lipase preparations are used as well as with pure PPL in the presence of bile salts and colipase. Lipases were found to have variable sensitivities to SBA inactivation, depending on their origin. In the presence of bile salts and tributyrin at pH 6.0, human gastric lipase activity was not affected by the presence of a 10(6) molar excess of SBA.

  6. Inactivation of RTEM beta-lactamase from Escherichia coli by clavulanic acid and 9-deoxyclavulanic acid.

    PubMed

    Charnas, R L; Knowles, J R

    1981-05-26

    The interaction of the TEM-2 beta-lactamase with 9-deoxyclavulanic acid (3) and with both extensively labeled (2) and specifically labeled (1) clavulanic acid has been studied. The close similarity between 9-doexyclavulanate and clavulanate in kinetics, spectroscopic, and protein chemical terms show that the allyl alcohol group of clavulanate is irrelevant to its action as a beta-lactamase inactivator. Use of the radiolabeled samples of clavulanate shows that, of three irreversibly inactivated forms of the enzymes, two contain the whole clavulanate skeleton and the third only retains the carbon atoms of the original beta-lactam ring. These findings allow the complex interaction between clavulanic acid and the beta-lactamase to be defined more narrowly in chemical terms.

  7. Cefoxitin inactivation by Bacteroides fragilis.

    PubMed

    Cuchural, G J; Tally, F P; Jacobus, N V; Marsh, P K; Mayhew, J W

    1983-12-01

    We have surveyed the susceptibility of 1,575 clinical isolates of the Bacteroides fragilis group of organisms to cefoxitin and eight other antimicrobial agents. Eleven isolates, 0.7% of the total, were highly cefoxitin resistant and had minimum inhibitory concentrations of greater than or equal to 64 micrograms/ml. These isolates were also resistant to other beta-lactam antibiotics. Of 11 isolates, 4 were able to inactivate cefoxitin in broth cultures, as measured by microbiological and high-pressure liquid chromatography assays. Two distinct patterns of cefoxitin breakdown products were detected by high-pressure liquid chromatography analysis. The beta-lactamase inhibitors clavulanic acid and sulbactam failed to show synergism with cefoxitin. These data demonstrate that members of the B. fragilis group have acquired a novel resistance mechanism enabling them to inactivate cefoxitin.

  8. Inactivation of allergens and toxins.

    PubMed

    Morandini, Piero

    2010-11-30

    Plants are replete with thousands of proteins and small molecules, many of which are species-specific, poisonous or dangerous. Over time humans have learned to avoid dangerous plants or inactivate many toxic components in food plants, but there is still room for ameliorating food crops (and plants in general) in terms of their allergens and toxins content, especially in their edible parts. Inactivation at the genetic rather than physical or chemical level has many advantages and classical genetic approaches have resulted in significant reduction of toxin content. The capacity, offered by genetic engineering, of turning off (inactivating) specific genes has opened up the possibility of altering the plant content in a far more precise manner than previously available. Different levels of intervention (genes coding for toxins/allergens or for enzymes, transporters or regulators involved in their metabolism) are possible and there are several tools for inactivating genes, both direct (using chemical and physical mutagens, insertion of transposons and other genetic elements) and indirect (antisense RNA, RNA interference, microRNA, eventually leading to gene silencing). Each level/strategy has specific advantages and disadvantages (speed, costs, selectivity, stability, reversibility, frequency of desired genotype and regulatory regime). Paradigmatic examples from classical and transgenic approaches are discussed to emphasize the need to revise the present regulatory process. Reducing the content of natural toxins is a trade-off process: the lesser the content of natural toxins, the higher the susceptibility of a plant to pests and therefore the stronger the need to protect plants. As a consequence, more specific pesticides like Bt are needed to substitute for general pesticides.

  9. Hydrazine vapor inactivates Bacillus spores

    NASA Astrophysics Data System (ADS)

    Schubert, Wayne W.; Engler, Diane L.; Beaudet, Robert A.

    2016-05-01

    NASA policy restricts the total number of bacterial spores that can remain on a spacecraft traveling to any planetary body which might harbor life or have evidence of past life. Hydrazine, N2H4, is commonly used as a propellant on spacecraft. Hydrazine as a liquid is known to inactivate bacterial spores. We have now verified that hydrazine vapor also inactivates bacterial spores. After Bacillus atrophaeus ATCC 9372 spores deposited on stainless steel coupons were exposed to saturated hydrazine vapor in closed containers, the spores were recovered from the coupons, serially diluted, pour plated and the surviving bacterial colonies were counted. The exposure times required to reduce the spore population by a factor of ten, known as the D-value, were 4.70 ± 0.50 h at 25 °C and 2.85 ± 0.13 h at 35 °C. These inactivation rates are short enough to ensure that the bioburden of the surfaces and volumes would be negligible after prolonged exposure to hydrazine vapor. Thus, all the propellant tubing and internal tank surfaces exposed to hydrazine vapor do not contribute to the total spore count.

  10. Factors limiting aliphatic chlorocarbon degradation by Nitrosomonas europaea: Cometabolic inactivation of ammonia monooxygenase and substrate specificity

    SciTech Connect

    Rasche, M.E.; Hyman, M.R.; Arp, D.J. )

    1991-10-01

    The soil nitrifying bacterium Nitrosomonas europaea is capable of degrading trichloroethylene (TCE) and other halogenated hydrocarbons. TCE cometabolism by N. europaea resulted in an irreversible loss of TCE biodegradative capacity, ammonia-oxidizing activity, and ammonia-dependent O{sub 2} uptake by the cells. Inactivation was not observed in the presence of allylthiourea, a specific inhibitor of enzyme ammonia monooxygenase, or under anaerobic conditions, indicating that the TCE-mediated inactivation required ammonia monooxygenase activity. When N. europaea cells were incubated with ({sup 14}C)TCE under conditions which allowed turnover of ammonia monooxygenase, a number of cellular proteins were covalently labeled with {sup 14}C. Treatment of cells with allylthiourea or acetylene prior to incubation with ({sup 14}C)TCE prevented incorporation of {sup 14}C into proteins. The ammonia-oxidizing activity of cells inactivated in the presence of TCE could be recovered through a process requiring de novo protein synthesis. In addition to TCE, a series of chlorinated methanes, ethanes, and other ethylenes were screened as substrates for ammonia monooxygenase and for their ability to inactivate the ammonia-oxidizing system of N. europaea. The chlorocarbons would be divided into three classes depending on their biodegradability and inactivating potential: (1) compounds which were not biodegradable by N. europaea and which had no toxic effect on the cells (2) compounds which were cooxidized by N. europaea and had little or no toxic effect on the cells; and (3) compounds which were cooxidized and produced a turnover-dependent inactivation of ammonia oxidation by N. europaea.

  11. Purification to homogeneity and partial amino acid sequence of a fragment which includes the methyl acceptor site of the human DNA repair protein for O6-methylguanine.

    PubMed

    Major, G N; Gardner, E J; Carne, A F; Lawley, P D

    1990-03-25

    DNA repair by O6-methylguanine-DNA methyltransferase (O6-MT) is accomplished by removal by the enzyme of the methyl group from premutagenic O6-methylguanine-DNA, thereby restoring native guanine in DNA. The methyl group is transferred to an acceptor site cysteine thiol group in the enzyme, which causes the irreversible inactivation of O6-MT. We detected a variety of different forms of the methylated, inactivated enzyme in crude extracts of human spleen of molecular weights higher and lower than the usually observed 21-24kDa for the human O6-MT. Several apparent fragments of the methylated form of the protein were purified to homogeneity following reaction of partially-purified extract enzyme with O6-[3H-CH3]methylguanine-DNA substrate. One of these fragments yielded amino acid sequence information spanning fifteen residues, which was identified as probably belonging to human methyltransferase by virtue of both its significant sequence homology to three procaryote forms of O6-MT encoded by the ada, ogt (both from E. coli) and dat (B. subtilis) genes, and sequence position of the radiolabelled methyl group which matched the position of the conserved procaryote methyl acceptor site cysteine residue. Statistical prediction of secondary structure indicated good homologies between the human fragment and corresponding regions of the constitutive form of O6-MT in procaryotes (ogt and dat gene products), but not with the inducible ada protein, indicating the possibility that we had obtained partial amino acid sequence for a non-inducible form of the human enzyme. The identity of the fragment sequence as belonging to human methyltransferase was more recently confirmed by comparison with cDNA-derived amino acid sequence from the cloned human O6-MT gene from HeLa cells (1). The two sequences compared well, with only three out of fifteen amino acids being different (and two of them by only one nucleotide in each codon).

  12. Intrinsic irreversibility limits the efficiency of multidimensional molecular motors

    NASA Astrophysics Data System (ADS)

    Jack, M. W.; Tumlin, C.

    2016-05-01

    We consider the efficiency limits of Brownian motors able to extract work from the temperature difference between reservoirs or from external thermodynamic forces. These systems can operate in a variety of modes, including as isothermal engines, heat engines, refrigerators, and heat pumps. We derive analytical results showing that certain classes of multidimensional Brownian motor, including the Smoluchowski-Feynman ratchet, are unable to attain perfect efficiency (Carnot efficiency for heat engines). This demonstrates the presence of intrinsic irreversibilities in their operating mechanism. We present numerical simulations showing that in some cases the loss process that limits efficiency is associated with vortices in the probability current.

  13. Typical pure nonequilibrium steady states and irreversibility for quantum transport.

    PubMed

    Monnai, Takaaki; Yuasa, Kazuya

    2016-07-01

    It is known that each single typical pure state in an energy shell of a large isolated quantum system well represents a thermal equilibrium state of the system. We show that such typicality holds also for nonequilibrium steady states (NESS's). We consider a small quantum system coupled to multiple infinite reservoirs. In the long run, the total system reaches a unique NESS. We identify a large Hilbert space from which pure states of the system are to be sampled randomly and show that the typical pure states well describe the NESS. We also point out that the irreversible relaxation to the unique NESS is important to the typicality of the pure NESS's.

  14. Irreversible shear-activated aggregation in non-Brownian suspensions.

    PubMed

    Guery, J; Bertrand, E; Rouzeau, C; Levitz, P; Weitz, D A; Bibette, J

    2006-05-19

    We have studied the effect of shear on the stability of suspensions made of non-Brownian solid particles. We demonstrate the existence of an irreversible transition where the solid particles aggregate at remarkably low volume fractions (phi approximately 0.1). This shear-induced aggregation is dramatic and exhibits a very sudden change in the viscosity, which increases sharply after a shear-dependent induction time. We show that this induction time is related exponentially to the shear rate, reflecting the importance of the hydrodynamic forces in reducing the repulsive energy barrier that prevents the particles from aggregating.

  15. Testing time series irreversibility using complex network methods

    NASA Astrophysics Data System (ADS)

    Donges, Jonathan F.; Donner, Reik V.; Kurths, Jürgen

    2013-04-01

    The absence of time-reversal symmetry is a fundamental property of many nonlinear time series. Here, we propose a new set of statistical tests for time series irreversibility based on standard and horizontal visibility graphs. Specifically, we statistically compare the distributions of time-directed variants of the common complex network measures degree and local clustering coefficient. Our approach does not involve surrogate data and is applicable to relatively short time series. We demonstrate its performance for paradigmatic model systems with known time-reversal properties as well as for picking up signatures of nonlinearity in neuro-physiological data.

  16. On Irreversibility and Radiation in Classical Electrodynamics of Point Particles

    NASA Astrophysics Data System (ADS)

    Bauer, Gernot; Deckert, Dirk-André; Dürr, Detlef; Hinrichs, Günter

    2013-09-01

    The direct interaction theory of electromagnetism, also known as Wheeler-Feynman electrodynamics, is often misinterpreted and found unappealing because of its reference to the absorber and, more importantly, to the so-called absorber condition. Here we remark that the absorber condition is indeed questionable and presumably not relevant for the explanation of irreversible radiation phenomena in our universe. What is relevant and deserves further scrutiny is the emergent effective description of a source particle in an environment. We therefore rephrase what we consider the relevant calculation by Wheeler and Feynman and comment on the status of the theory.

  17. Irreversible electroporation of hepatocellular carcinoma: patient selection and perspectives

    PubMed Central

    Zimmerman, Asha; Grand, David; Charpentier, Kevin P

    2017-01-01

    Irreversible electroporation (IRE) is a novel form of tissue ablation that uses high-current electrical pulses to induce pore formation of the cell lipid bilayer, leading to cell death. The safety of IRE for ablation of hepatocellular carcinoma (HCC) has been established. Outcome data for ablation of HCC by IRE are limited, but early results are encouraging and suggest equivalency to the outcomes obtained for thermal ablation for appropriately selected, small (<3 cm) tumors. Long-term oncologic efficacy and histopathologic response data have not been published, and therefore, application of IRE for the treatment of HCC should still be viewed with caution. PMID:28331845

  18. The inhaled glucocorticoid fluticasone propionate efficiently inactivates cytochrome P450 3A5, a predominant lung P450 enzyme

    PubMed Central

    Murai, Takahiro; Reilly, Christopher R.; Ward, Robert M.; Yost, Garold S.

    2010-01-01

    Inhaled glucocorticoid (GC) therapy is a vital part of the management of chronic asthma. GCs are metabolized by members of the cytochrome P450 3A family in both liver and lung, but the enzymes are differentially expressed. Selective inhibition of one or more P450 3A enzymes could substantially modify target and systemic concentrations of GCs. In this study, we have evaluated the mechanism-based inactivation of P450 3A4, 3A5 and 3A7 enzymes by GCs. Among the five major inhaled GCs approved for clinical use in the United States, fluticasone propionate (FLT) was the most potent mechanism-based inactivator of P450 3A5, the predominant P450 enzyme in the lung. FLT inactivated P450 3A5 in a time- and concentration-dependent manner with KI, kinact and partition ratio of 16 μM, 0.027 min-1 and 3, respectively. In contrast, FLT minimally inactivated P450 3A4 and did not inactivate 3A7, even with a concentration of 100 μM. The inactivation of P450 3A5 by FLT was irreversible because dialysis did not restore enzyme activity. In addition, the exogenous nucleophilic scavenger GSH did not attenuate inactivation. The prosthetic heme of P450 3A5 was not modified by FLT. The loss of P450 3A5 activity in lung cells could substantially decrease the metabolism of FLT, which would increase the effective FLT concentration at its target site, the respiratory epithelium. Also, inactivation of lung P450 3A5 could increase the absorption of inhaled FLT, which could lead to high systemic concentrations and adverse effects, such as life-threatening adrenal crises or cataracts that have been documented in children receiving high doses of inhaled GCs. PMID:20707410

  19. From Maximum Entropy Models to Non-Stationarity and Irreversibility

    NASA Astrophysics Data System (ADS)

    Cofre, Rodrigo; Cessac, Bruno; Maldonado, Cesar

    The maximum entropy distribution can be obtained from a variational principle. This is important as a matter of principle and for the purpose of finding approximate solutions. One can exploit this fact to obtain relevant information about the underlying stochastic process. We report here in recent progress in three aspects to this approach.1- Biological systems are expected to show some degree of irreversibility in time. Based on the transfer matrix technique to find the spatio-temporal maximum entropy distribution, we build a framework to quantify the degree of irreversibility of any maximum entropy distribution.2- The maximum entropy solution is characterized by a functional called Gibbs free energy (solution of the variational principle). The Legendre transformation of this functional is the rate function, which controls the speed of convergence of empirical averages to their ergodic mean. We show how the correct description of this functional is determinant for a more rigorous characterization of first and higher order phase transitions.3- We assess the impact of a weak time-dependent external stimulus on the collective statistics of spiking neuronal networks. We show how to evaluate this impact on any higher order spatio-temporal correlation. RC supported by ERC advanced Grant ``Bridges'', BC: KEOPS ANR-CONICYT, Renvision and CM: CONICYT-FONDECYT No. 3140572.

  20. Voter model with arbitrary degree dependence: clout, confidence and irreversibility

    NASA Astrophysics Data System (ADS)

    Fotouhi, Babak; Rabbat, Michael G.

    2014-03-01

    The voter model is widely used to model opinion dynamics in society. In this paper, we propose three modifications to incorporate heterogeneity into the model. We address the corresponding oversimplifications of the conventional voter model which are unrealistic. We first consider the voter model with popularity bias. The influence of each node on its neighbors depends on its degree. We find the consensus probabilities and expected consensus times for each of the states. We also find the fixation probability, which is the probability that a single node whose state differs from every other node imposes its state on the entire system. In addition, we find the expected fixation time. Then two other extensions to the model are proposed and the motivations behind them are discussed. The first one is confidence, where in addition to the states of neighbors, nodes take their own state into account at each update. We repeat the calculations for the augmented model and investigate the effects of adding confidence to the model. The second proposed extension is irreversibility, where one of the states is given the property that once nodes adopt it, they cannot switch back. This is motivated by applications where, agents take an irreversible action such as seeing a movie, purchasing a music album online, or buying a new product. The dynamics of densities, fixation times and consensus times are obtained.

  1. Endovascular nonthermal irreversible electroporation: a finite element analysis.

    PubMed

    Maor, Elad; Rubinsky, Boris

    2010-03-01

    Tissue ablation finds an increasing use in modern medicine. Nonthermal irreversible electroporation (NTIRE) is a biophysical phenomenon and an emerging novel tissue ablation modality, in which electric fields are applied in a pulsed mode to produce nanoscale defects to the cell membrane phospholipid bilayer, in such a way that Joule heating is minimized and thermal damage to other molecules in the treated volume is reduced while the cells die. Here we present a two-dimensional transient finite element model to simulate the electric field and thermal damage to the arterial wall due to an endovascular NTIRE novel device. The electric field was used to calculate the Joule heating effect, and a transient solution of the temperature is presented using the Pennes bioheat equation. This is followed by a kinetic model of the thermal damage based on the Arrhenius formulation and calculation of the Henriques and Moritz thermal damage integral. The analysis shows that the endovascular application of 90, 100 mus pulses with a potential difference of 600 V can induce electric fields of 1000 V/cm and above across the entire arterial wall, which are sufficient for irreversible electroporation. The temperature in the arterial wall reached a maximum of 66.7 degrees C with a pulse frequency of 4 Hz. Thermal damage integral showed that this protocol will thermally damage less than 2% of the molecules around the electrodes. In conclusion, endovascular NTIRE is possible. Our study sets the theoretical basis for further preclinical and clinical trials with endovascular NTIRE.

  2. Frequency spectroscopy of irreversible electrochemical nucleation kinetics on the nanoscale

    NASA Astrophysics Data System (ADS)

    Kumar, Amit; Chen, Chi; Arruda, Thomas M.; Jesse, Stephen; Ciucci, Francesco; Kalinin, Sergei V.

    2013-11-01

    An approach is developed for probing the thermodynamics and kinetics of irreversible electrochemical reactions on solid surfaces based on local frequency-voltage spectroscopy. For a model Li-ion conductor surface, two regimes for bias-controlled behavior are demonstrated and ascribed to the difference in the critical nucleus size. The electrostatic and electrochemical phenomena at the tip-surface junction are analyzed. These studies suggest an experimental pathway for exploring local electrochemical activity in solids.An approach is developed for probing the thermodynamics and kinetics of irreversible electrochemical reactions on solid surfaces based on local frequency-voltage spectroscopy. For a model Li-ion conductor surface, two regimes for bias-controlled behavior are demonstrated and ascribed to the difference in the critical nucleus size. The electrostatic and electrochemical phenomena at the tip-surface junction are analyzed. These studies suggest an experimental pathway for exploring local electrochemical activity in solids. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr03953f

  3. MTA pulpotomy of human permanent molars with irreversible pulpitis.

    PubMed

    Eghbal, Mohammad Jafar; Asgary, Saeed; Baglue, Reza Ali; Parirokh, Masoud; Ghoddusi, Jamileh

    2009-04-01

    The histological success of mineral trioxide aggregate (MTA) pulpotomy for treatment of irreversible pulpitis in human teeth as an alternative treatment was investigated in this study. Fourteen molars which had to be extracted were selected from patients 16-28 years old. The selection criteria include carious pulp exposure with a history of lingering pain. After isolation, caries removal and pulp exposure, MTA was used in pulpotomy treatment. Patients were evaluated for pain after 24 h. Two patients were lost from this study. Twelve teeth were extracted after 2 months and were assessed histologically. Recall examinations confirmed that none of the patients experienced pain after pulpotomy. Histological observation revealed that all samples had dentin bridge formation completely and that the pulps were vital and free of inflammation. Although the results favour the use of MTA as a pulpotomy material, more studies with larger samples and a longer recall period are suggested to justify the use of MTA for treatment of irreversible pulpitis in human permanent teeth.

  4. Critical behavior of an irreversible multiple-reaction process

    NASA Astrophysics Data System (ADS)

    Albano, Ezequiel V.

    1994-04-01

    A multiple-reaction irreversible surface reaction model (M-R) involving one monomer (A) and two different dimers (B 2 and C 2) is proposed and studied by means of Monte Carlo simulations. In the absence of the monomer species the M-R model reduces to the DD model (Maltz et al. Surf. Sci. 277 (1992) 414), while in the absence of one of the dimer species the M-R gives the ZGB model (Ziff et al. Phys. Rev. Lett. 56 (1986) 2553). The M-R model is suitable to investigate: on the one hand, the influence caused by the presence of H 2-traces (H 2 is C 2) on the catalytic oxidation of carbon monoxide, e.g. A + {1}/{2})B 2 → AB where A is CO, B 2 is O 2 and AB is CO 2, and on the other hand, the effect of CO-traces on the catalytic oxidation of hydrogen, e.g. ( {1}/{2})B 2 + C 2 → C 2B. Furthermore, the M-R model exhibits irreversible phase transitions (IPTs) between poisoned states with the surface saturated by adsorbed species and reactive regimes with production of both AB and C 2B. The critical points at which the first and second-order IPTs characteristic of the M-R take place are determined. Interesting theoretical possibilities which become opened when studying the observed critical behavior of the M-R model are discussed.

  5. Linear Dimensional Stability of Irreversible Hydrocolloid Materials Over Time.

    PubMed

    Garrofé, Analía B; Ferrari, Beatriz A; Picca, Mariana; Kaplan, Andrea E

    2015-12-01

    The aim of this study was to evaluate the linear dimensional stability of different irreversible hydrocolloid materials over time. A metal mold was designed with custom trays made of thermoplastic sheets (Sabilex, sheets 0.125 mm thick). Perforations were made in order to improve retention of the material. Five impressions were taken with each of the following: Kromopan 100 (LASCOD) [AlKr], which has dimensional stability of 100 hours, and Phase Plus (ZHERMACK) [AlPh], which has dimensional stability of 48 hours. Standardized digital photographs were taken at different time intervals (0, 15, 30, 45, 60, 120 minutes; 12, 24 and 96 hours), using an "ad-hoc" device. The images were analyzed with software (UTHSCSA Image Tool) by measuring the distance between intersection of the lines previously made at the top of the mold. The results were analyzed by ANOVA for repeated measures. Initial and final values were (mean and standard deviation): AlKr: 16.44 (0.22) and 16.34 (0.11), AlPh: 16.40 (0.06) and 16.18 (0.06). Statistical evaluation showed significant effect of material and time factors. Under the conditions in this study, time significantly affects the linear dimensional stability of irreversible hydrocolloid materials.

  6. Irreversible entropy model for damage diagnosis in resistors

    SciTech Connect

    Cuadras, Angel Crisóstomo, Javier; Ovejas, Victoria J.; Quilez, Marcos

    2015-10-28

    We propose a method to characterize electrical resistor damage based on entropy measurements. Irreversible entropy and the rate at which it is generated are more convenient parameters than resistance for describing damage because they are essentially positive in virtue of the second law of thermodynamics, whereas resistance may increase or decrease depending on the degradation mechanism. Commercial resistors were tested in order to characterize the damage induced by power surges. Resistors were biased with constant and pulsed voltage signals, leading to power dissipation in the range of 4–8 W, which is well above the 0.25 W nominal power to initiate failure. Entropy was inferred from the added power and temperature evolution. A model is proposed to understand the relationship among resistance, entropy, and damage. The power surge dissipates into heat (Joule effect) and damages the resistor. The results show a correlation between entropy generation rate and resistor failure. We conclude that damage can be conveniently assessed from irreversible entropy generation. Our results for resistors can be easily extrapolated to other systems or machines that can be modeled based on their resistance.

  7. Carnot's cycle for small systems: Irreversibility and cost of operations

    NASA Astrophysics Data System (ADS)

    Sekimoto, Ken; Takagi, Fumiko; Hondou, Tsuyoshi

    2000-12-01

    In the thermodynamic limit, the existence of a maximal efficiency of energy conversion attainable by a Carnot cycle consisting of quasistatic isothermal and adiabatic processes precludes the existence of a perpetual machine of the second kind, whose cycles yield positive work in an isothermal environment. We employ the recently developed framework of the energetics of stochastic processes (called ``stochastic energetics'') to reanalyze the Carnot cycle in detail, taking account of fluctuations, without taking the thermodynamic limit. We find that in this nonmacroscopic situation both processes of connection to and disconnection from heat baths and adiabatic processes that cause distortion of the energy distribution are sources of inevitable irreversibility within the cycle. Also, the so-called null-recurrence property of the cumulative efficiency of energy conversion over many cycles and the irreversible property of isolated, purely mechanical processes under external ``macroscopic'' operations are discussed in relation to the impossibility of a perpetual machine, or Maxwell's demon. This analysis may serve as the basis for the design and analysis of mesoscopic energy converters in the near future.

  8. Influence of delayed pouring on irreversible hydrocolloid properties.

    PubMed

    Rodrigues, Stéfani Becker; Augusto, Carolina Rocha; Leitune, Vicente Castelo Branco; Samuel, Susana Maria Werner; Collares, Fabrício Mezzomo

    2012-01-01

    The aim of this study was to evaluate the physical properties of irreversible hydrocolloid materials poured immediately and after different storage periods. Four alginates were tested: Color Change (Cavex); Hydrogum (Zhermack); Hydrogum 5 (Zhermack); and Hydro Print Premium (Coltene). Their physical properties, including the recovery from deformation (n = 3), compressive strength (n = 3), and detail reproduction and gypsum compatibility (n = 3), were analyzed according to ANSI/ADA specification no. 18. Specimens were stored at 23ºC and humidity and were then poured with gypsum immediately and after 1, 2, 3, 4, and 5 days. The data were analyzed by two-way analysis of variance (ANOVA) and Tukey's test at p < 0.05. All of the alginate impression materials tested exhibited detail reproduction and gypsum compatibility at all times. Hydro Print Premium and Hydrogum 5 showed recovery from deformation, as established by ANSI/ADA specification no. 18, after 5 days of storage. As the storage time increased, the compressive strength values also increased. Considering the properties of compounds' recovery from deformation, compressive strength, and detail reproduction and gypsum compatibility, irreversible hydrocolloids should be poured immediately.

  9. Irreversibility in physics stemming from unpredictable symbol-handling agents

    NASA Astrophysics Data System (ADS)

    Myers, John M.; Madjid, F. Hadi

    2016-05-01

    The basic equations of physics involve a time variable t and are invariant under the transformation t --> -t. This invariance at first sight appears to impose time reversibility as a principle of physics, in conflict with thermodynamics. But equations written on the blackboard are not the whole story in physics. In prior work we sharpened a distinction obscured in today's theoretical physics, the distinction between obtaining evidence from experiments on the laboratory bench and explaining that evidence in mathematical symbols on the blackboard. The sharp distinction rests on a proof within the mathematics of quantum theory that no amount of evidence, represented in quantum theory in terms of probabilities, can uniquely determine its explanation in terms of wave functions and linear operators. Building on the proof we show here a role in physics for unpredictable symbol-handling agents acting both at the blackboard and at the workbench, communicating back and forth by means of transmitted symbols. Because of their unpredictability, symbol-handling agents introduce a heretofore overlooked source of irreversibility into physics, even when the equations they write on the blackboard are invariant under t --> -t. Widening the scope of descriptions admissible to physics to include the agents and the symbols that link theory to experiments opens up a new source of time-irreversibility in physics.

  10. Evidence of irreversible CO2 intercalation in montmorillonite

    SciTech Connect

    Romanov, V

    2013-02-13

    Mitigation of the global climate change via sequestration of anthropogenic carbon dioxide (CO2) in geologic formations requires assessment of the reservoir storage capacity and cap rock seal integrity. The typical cap rock is shale or mudstone rich in clay minerals that may significantly affect the effectiveness of the CO2 trapping. Specific objectives of this study were to conduct experimental investigation into the processes associated with CO2 and H2O trapped in swelling clay, namely, Wyoming and Texas montmorillonite powder. Combined (same-sample) multi-technique data ? manometric sorption isotherm hysteresis, diffuse reflectance infrared spectroscopy ?trapped CO2? fingerprints, irreversible X-ray diffraction patterns for the clay interlayer in intermediate hydration state, and HF acid digestion resulting in formation of non-extractable F:CO2 adducts ? corroborate a hypothesis that carbon dioxide molecules can be irreversibly trapped via anomalous extreme confinement in the galleries associated with montmorillonite interlayer, which may result in formation of carbonates in the longer term. Validation on Arizona montmorillonite lumps substantiated the evidence that such processes may occur in natural clay deposits but possibly on a different scale and at a different rate.

  11. Chromosomal rearrangement interferes with meiotic X chromosome inactivation.

    PubMed

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-10-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC). Here, we report on the transcriptional down-regulation of genes within the unsynapsed region of the rearranged mouse chromosome 17, and on the subsequent disturbance of X chromosome inactivation. The partial transcriptional suppression of genes in the unsynapsed chromatin was most prominent prior to the mid-pachytene stage of primary spermatocytes. Later, during the mid-late pachytene, the rearranged autosomes colocalized with the XY body, and the X chromosome failed to undergo proper transcriptional silencing. Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation.

  12. Pressure Inactivation of Bacillus Endospores

    PubMed Central

    Margosch, Dirk; Gänzle, Michael G.; Ehrmann, Matthias A.; Vogel, Rudi F.

    2004-01-01

    The inactivation of bacterial endospores by hydrostatic pressure requires the combined application of heat and pressure. We have determined the resistance of spores of 14 food isolates and 5 laboratory strains of Bacillus subtilis, B. amyloliquefaciens, and B. licheniformis to treatments with pressure and temperature (200 to 800 MPa and 60 to 80°C) in mashed carrots. A large variation in the pressure resistance of spores was observed, and their reduction by treatments with 800 MPa and 70°C for 4 min ranged from more than 6 log units to no reduction. The sporulation conditions further influenced their pressure resistance. The loss of dipicolinic acid (DPA) from spores that varied in their pressure resistance was determined, and spore sublethal injury was assessed by determination of the detection times for individual spores. Treatment of spores with pressure and temperature resulted in DPA-free, phase-bright spores. These spores were sensitive to moderate heat and exhibited strongly increased detection times as judged by the time required for single spores to grow to visible turbidity of the growth medium. The role of DPA in heat and pressure resistance was further substantiated by the use of the DPA-deficient mutant strain B. subtilis CIP 76.26. Taken together, these results indicate that inactivation of spores by combined pressure and temperature processing is achieved by a two-stage mechanism that does not involve germination. At a pressure between 600 and 800 MPa and a temperature greater than 60°C, DPA is released predominantly by a physicochemical rather than a physiological process, and the DPA-free spores are inactivated by moderate heat independent of the pressure level. Relevant target organisms for pressure and temperature treatment of foods are proposed, namely, strains of B. amyloliquefaciens, which form highly pressure-resistant spores. PMID:15574932

  13. Photocatalytic bacterial inactivation by polyoxometalates.

    PubMed

    Bae, Eunyoung; Lee, Jae Won; Hwang, Byeong Hee; Yeo, Jiman; Yoon, Jeyong; Cha, Hyung Joon; Choi, Wonyong

    2008-05-01

    The photocatalytic inactivation (PCI) of Escherichia coli (Gram-negative) and Bacillus subtilis (Gram-positive) was performed using polyoxometalate (POM) as a homogeneous photocatalyst and compared with that of heterogeneous TiO2 photocatalyst. Aqueous suspensions of the microorganisms (10(7)-10(8)cfu ml(-1)) and POM (or TiO2) were irradiated with black light lamps. The POM-PCI was faster than (or comparable to) TiO2-PCI under the experimental conditions employed in this study. The relative efficiency of POM-PCI was species-dependent. Among three POMs (H(3)PW(12)O(40), H(3)PMo(12)O(40), and H(4)SiW(12)O(40)) tested in this study, the inactivation of E. coli was fastest with H(4)SiW(12)O(40) while that of B. subtilis was the most efficient with H(3)PW(12)O(40). Although the biocidal action of TiO2 photocatalyst has been commonly ascribed to the role of photogenerated reactive oxygen species such as hydroxyl radicals and superoxides, the cell death mechanism with POM seems to be different from TiO2-PCI. While TiO2 caused the cell membrane disruption, POM did not induce the cell lysis. When methanol was added to the POM solution, not only the PCI of E. coli was enhanced (contrary to the case of TiO2-PCI) but also the dark inactivation was observed. This was ascribed to the in situ production of formaldehyde from the oxidation of methanol. The interesting biocidal property of POM photocatalyst might be utilized as a potential disinfectant technology.

  14. Phenol derivatives accelerate inactivation kinetics in one inactivation-deficient mutant human skeletal muscle Na(+) channel.

    PubMed

    Haeseler, G; Piepenbrink, A; Bufler, J; Dengler, R; Hecker, H; Aronson, J; Piepenbrock, S; Leuwer, M

    2001-03-23

    Altered inactivation kinetics in skeletal muscle Na(+) channels due to mutations in the encoding gene are causal for the alterations in muscle excitability in nondystrophic myotonia. Na(+) channel blockers like lidocaine and mexiletine, suggested for therapy of myotonia, do not reconstitute inactivation in channels with defective inactivation in vitro. We examined the effects of four methylated and/or halogenated phenol derivatives on one heterologously expressed inactivation-deficient Paramyotonia congenita-mutant (R1448H) muscle Na(+) channel in vitro. All these compounds accelerated delayed inactivation of R1448H-whole-cell currents during a depolarization and delayed accelerated recovery from inactivation. The potency of these effects paralleled the potency of the drugs to block the peak current amplitude. We conclude that the investigated phenol derivatives affect inactivation-deficient Na(+) channels more specifically than lidocaine and mexiletine. However, for all compounds, the effect on inactivation was accompanied by a substantial block of the peak current amplitude.

  15. Modeling of human factor Va inactivation by activated protein C

    PubMed Central

    2012-01-01

    Background Because understanding of the inventory, connectivity and dynamics of the components characterizing the process of coagulation is relatively mature, it has become an attractive target for physiochemical modeling. Such models can potentially improve the design of therapeutics. The prothrombinase complex (composed of the protease factor (F)Xa and its cofactor FVa) plays a central role in this network as the main producer of thrombin, which catalyses both the activation of platelets and the conversion of fibrinogen to fibrin, the main substances of a clot. A key negative feedback loop that prevents clot propagation beyond the site of injury is the thrombin-dependent generation of activated protein C (APC), an enzyme that inactivates FVa, thus neutralizing the prothrombinase complex. APC inactivation of FVa is complex, involving the production of partially active intermediates and “protection” of FVa from APC by both FXa and prothrombin. An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation. Results A model of human APC inactivation of prothrombinase was constructed in a stepwise fashion by analyzing time courses of FVa inactivation in empirical reaction systems with increasing number of interacting components and generating corresponding model constructs of each reaction system. Reaction mechanisms, rate constants and equilibrium constants informing these model constructs were initially derived from various research groups reporting on APC inactivation of FVa in isolation, or in the presence of FXa or prothrombin. Model predictions were assessed against empirical data measuring the appearance and disappearance of multiple FVa degradation intermediates as well as prothrombinase activity changes, with plasma proteins derived from multiple preparations. Our work integrates previously published findings and through the cooperative analysis of in vitro

  16. Charge Immobilization of Skeletal Muscle Na+ Channels: Role of Residues in the Inactivation Linker

    PubMed Central

    Groome, James R.; Dice, Margaret C.; Fujimoto, Esther; Ruben, Peter C.

    2007-01-01

    We investigated structural determinants of fast inactivation and deactivation in sodium channels by comparing ionic flux and charge movement in skeletal muscle channels, using mutations of DIII-DIV linker charges. Charge altering and substituting mutations at K-1317, K-1318 depolarized the g(V) curve but hyperpolarized the h∞ curve. Charge reversal and substitution at this locus reduced the apparent voltage sensitivity of open- and closed-state fast inactivation. These effects were not observed with charge reversal at E-1314, E-1315. Mutations swapping or neutralizing the negative cluster at 1314, 1315 and the positive cluster at 1317, 1318 indicated that local interactions dictate the coupling of activation to fast inactivation. Gating charge was immobilized before channel entry into fast inactivation in hNaV1.4 but to a lesser extent in mutations at K-1317, K-1318. These results suggest that charge is preferentially immobilized in channels inactivating from the open state. Recovery of gating charge proceeded with a single, fast phase in the double mutation K-1317R, K-1318R. This mutation also partially uncoupled recovery from deactivation. Our findings indicate that charged residues near the fast inactivation “particle” allosterically interact with voltage sensors to control aspects of gating in sodium channels. PMID:17513361

  17. Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates

    PubMed Central

    Fahey, Jed W.; Stephenson, Katherine K.; Wade, Kristina L.; Talalay, Paul

    2013-01-01

    Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 280–340 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections. PMID:23583386

  18. Irreversible thermochromism in copper chloride Imidazolium Nanoparticle Networks.

    PubMed

    Kronstein, Martin; Kriechbaum, Konstantin; Akbarzadeh, Johanna; Peterlik, Herwig; Neouze, Marie-Alexandra

    2013-08-14

    In this work Imidazolium Nanoparticle Networks (INNs) with chloride counter-ions were used to complex copper dichloride. This complexation reaction leads to the formation of a green material. The properties of the copper INN material were compared to: first, copper imidazolium complexes, without the presence of silica nanoparticles, which are not thermochromic; second, chloride-containing INN material. The copper INN material showed irreversible thermochromic behaviour, with a clear colour change from green to yellow at 180 °C, which is due to a configuration change of the copper complex from planar to tetragonal. This structural change was studied using DSC and in situ SAXS measurements during heat treatment. The thermochromic material is stable under air up to 250 °C. This preliminary study opens the door of optical sensors for INN materials.

  19. Exact solutions for mass-dependent irreversible aggregations.

    PubMed

    Son, Seung-Woo; Christensen, Claire; Bizhani, Golnoosh; Grassberger, Peter; Paczuski, Maya

    2011-10-01

    We consider the mass-dependent aggregation process (k+1)X→X, given a fixed number of unit mass particles in the initial state. One cluster is chosen proportional to its mass and is merged into one, either with k neighbors in one dimension, or--in the well-mixed case--with k other clusters picked randomly. We find the same combinatorial exact solutions for the probability to find any given configuration of particles on a ring or line, and in the well-mixed case. The mass distribution of a single cluster exhibits scaling laws and the finite-size scaling form is given. The relation to the classical sum kernel of irreversible aggregation is discussed.

  20. Rat liver regeneration following ablation with irreversible electroporation

    PubMed Central

    Bruinsma, Bote G.; Jaramillo, Maria; Yarmush, Martin L.

    2016-01-01

    During the past decade, irreversible electroporation (IRE) ablation has emerged as a promising tool for the treatment of multiple diseases including hepatic cancer. However, the mechanisms behind the tissue regeneration following IRE ablation have not been investigated. Our results indicate that IRE treatment immediately kills the cells at the treatment site preserving the extracellular architecture, in effect causing in vivo decellularization. Over the course of 4 weeks, progenitor cell differentiation, through YAP and notch pathways, together with hepatocyte expansion led to almost complete regeneration of the ablated liver leading to the formation of hepatocyte like cells at the ablated zone. We did not observe significant scarring or tumor formation at the regenerated areas 6 months post IRE. Our study suggests a new model to study the regeneration of liver when the naïve extracellular matrix is decellularized in vivo with completely preserved extracellular architecture. PMID:26819842

  1. Rat liver regeneration following ablation with irreversible electroporation.

    PubMed

    Golberg, Alexander; Bruinsma, Bote G; Jaramillo, Maria; Yarmush, Martin L; Uygun, Basak E

    2016-01-01

    During the past decade, irreversible electroporation (IRE) ablation has emerged as a promising tool for the treatment of multiple diseases including hepatic cancer. However, the mechanisms behind the tissue regeneration following IRE ablation have not been investigated. Our results indicate that IRE treatment immediately kills the cells at the treatment site preserving the extracellular architecture, in effect causing in vivo decellularization. Over the course of 4 weeks, progenitor cell differentiation, through YAP and notch pathways, together with hepatocyte expansion led to almost complete regeneration of the ablated liver leading to the formation of hepatocyte like cells at the ablated zone. We did not observe significant scarring or tumor formation at the regenerated areas 6 months post IRE. Our study suggests a new model to study the regeneration of liver when the naïve extracellular matrix is decellularized in vivo with completely preserved extracellular architecture.

  2. Large-cell Monte Carlo renormalization of irreversible growth processes

    NASA Technical Reports Server (NTRS)

    Nakanishi, H.; Family, F.

    1985-01-01

    Monte Carlo sampling is applied to a recently formulated direct-cell renormalization method for irreversible, disorderly growth processes. Large-cell Monte Carlo renormalization is carried out for various nonequilibrium problems based on the formulation dealing with relative probabilities. Specifically, the method is demonstrated by application to the 'true' self-avoiding walk and the Eden model of growing animals for d = 2, 3, and 4 and to the invasion percolation problem for d = 2 and 3. The results are asymptotically in agreement with expectations; however, unexpected complications arise, suggesting the possibility of crossovers, and in any case, demonstrating the danger of using small cells alone, because of the very slow convergence as the cell size b is extrapolated to infinity. The difficulty of applying the present method to the diffusion-limited-aggregation model, is commented on.

  3. Sub-kBT micro-electromechanical irreversible logic gate.

    PubMed

    López-Suárez, M; Neri, I; Gammaitoni, L

    2016-06-28

    In modern computers, computation is performed by assembling together sets of logic gates. Popular gates like AND, OR and XOR, processing two logic inputs and yielding one logic output, are often addressed as irreversible logic gates, where the sole knowledge of the output logic value is not sufficient to infer the logic value of the two inputs. Such gates are usually believed to be bounded to dissipate a finite minimum amount of energy determined by the input-output information difference. Here we show that this is not necessarily the case, by presenting an experiment where a OR logic gate, realized with a micro-electromechanical cantilever, is operated with energy well below the expected limit, provided the operation is slow enough and frictional phenomena are properly addressed.

  4. Sub-kBT micro-electromechanical irreversible logic gate

    PubMed Central

    López-Suárez, M.; Neri, I.

    2016-01-01

    In modern computers, computation is performed by assembling together sets of logic gates. Popular gates like AND, OR and XOR, processing two logic inputs and yielding one logic output, are often addressed as irreversible logic gates, where the sole knowledge of the output logic value is not sufficient to infer the logic value of the two inputs. Such gates are usually believed to be bounded to dissipate a finite minimum amount of energy determined by the input–output information difference. Here we show that this is not necessarily the case, by presenting an experiment where a OR logic gate, realized with a micro-electromechanical cantilever, is operated with energy well below the expected limit, provided the operation is slow enough and frictional phenomena are properly addressed. PMID:27350333

  5. Ac irreversibility line of bismuth-based high temperature superconductors

    SciTech Connect

    Mehdaoui, A.; Beille, J.; Berling, D.; Loegel, B.; Noudem, J.G.; Tournier, R.

    1997-09-01

    We discuss the magnetic properties of lead doped Bi-2223 bulk samples obtained through combined magnetic melt texturing and hot pressing (MMTHP). The ac complex susceptibility measurements are achieved over a broad ac field range (1 Oe{lt}h{sub ac}{lt}100 Oe) and show highly anisotropic properties. The intergranular coupling is improved in the direction perpendicular to the applied stress and magnetic field direction, and an intragranular loss peak is observed for the first time. A comparison is made with other bismuth-based compounds and it is shown that the MMTHP process shifts the ac irreversibility line (ac IL) toward higher fields. It is also shown that all the ac IL{close_quote}s for quasi 2D bismuth-based compounds show a nearly quadratic temperature dependence and deviate therefore strongly from the linear behavior observed in quasi 3D compounds and expected from a critical state model.{copyright} {ital 1997 Materials Research Society.}

  6. Citrate synthesis in intact rat-liver mitochondria is irreversible.

    PubMed

    Greksák, M; Lopes-Cardozo, M; van den Bergh, S G

    1982-02-01

    Rat-liver mitochondria were incubated with [1,5-14C]citrate in the presence of fluorocitrate to block its oxidation in the Krebs cycle. The reaction products were analysed enzymatically and by anion-exchange chromatography. Incorporation of 14C into acetyl-L-carnitine or ketone bodies via a backward action of citrate synthase was not observed. The optimal rate of citrate synthesis from pyruvate and malate in the presence of fluorocitrate was 15 nmol . mg-1 min-1. In the absence of fluorocitrate, but in the presence of malonate, citrate was oxidized to succinate at a rate of 4 nmol . mg-1 . min-1. We conclude that the synthesis of citrate by intact rat liver mitochondria is an irreversible process. The possible mechanism underlying this phenomenon and the consequence for metabolic regulation are discussed.

  7. Irreversible electroporation for the treatment of pancreatic neuroendocrine tumors

    PubMed Central

    Papamichail, Michail; Ali, Amir; Pizanias, Michail; Peddu, Praveen; Karani, John

    2016-01-01

    Backgrounds/Aims Resection or enucleation is currently the treatment of choice for small pancreatic neuroendocrine tumors (NETs). Irreversible electroporation is a novel ablative method that is used for locally advanced pancreatic adenocarcinoma, but little data exists for its use for pancreatic NETs. We report an early experience of IRE for early pancreatic NETs. Methods Between April 2014 and March 2015, 3 patients with small (<2 cm) pancreatic NETs were treated with percutaneous IRE. Results There were no adverse effects during the procedure. Mean hospital stay was 2.6 days. All patients remained disease free on 12-19 months follow up. One patient developed recurrent pancreatitis with pseudocyst formation. Conclusions IRE for small tumors of the pancreas is practical and may offer advantages over other thermal ablative techniques, since it preserves vital structures such as blood vessels, bile and pancreatic ducts. Further data regarding the long term disease free interval is required to establish efficacy. PMID:27621748

  8. Advertising and Irreversible Opinion Spreading in Complex Social Networks

    NASA Astrophysics Data System (ADS)

    Candia, Julián

    Irreversible opinion spreading phenomena are studied on small-world and scale-free networks by means of the magnetic Eden model, a nonequilibrium kinetic model for the growth of binary mixtures in contact with a thermal bath. In this model, the opinion of an individual is affected by those of their acquaintances, but opinion changes (analogous to spin flips in an Ising-like model) are not allowed. We focus on the influence of advertising, which is represented by external magnetic fields. The interplay and competition between temperature and fields lead to order-disorder transitions, which are found to also depend on the link density and the topology of the complex network substrate. The effects of advertising campaigns with variable duration, as well as the best cost-effective strategies to achieve consensus within different scenarios, are also discussed.

  9. [Irreversible coma following hypoglycemia in Sheehan syndrome with adrenocortical insufficiency].

    PubMed

    Sas, A M; Meynaar, I A; Laven, J S; Bakker, S L; Feelders, R A

    2003-08-23

    A 24-year-old woman of Somali origin delivered at term after an uncomplicated pregnancy. Post-partum haemorrhage resulted in hypovolaemic shock which was treated by hysterectomy. Five days later she became comatose due to unrecognised hypoglycaemia which caused severe irreversible brain damage and status epilepticus. Treatment in the intensive care unit with artificial respiration, prednisolone, desmopressin, inotropic support, barbiturates and an anaesthetic under EEG guidance was unsuccessful. The patient died 28 days post-partum. The hypoglycaemia was due to a combination of (a) inadequate glucose intake and (b) lack of counter-regulatory mechanisms due to a deficiency of steroids and growth hormone as a result of loss of pituitary function (Sheehan syndrome) together with adrenocortical insufficiency. The combination of Sheehan syndrome and primary adrenocortical insufficiency has not been described previously in the literature.

  10. Independent evolution of transcriptional inactivation on sex chromosomes in birds and mammals.

    PubMed

    Livernois, Alexandra M; Waters, Shafagh A; Deakin, Janine E; Marshall Graves, Jennifer A; Waters, Paul D

    2013-01-01

    X chromosome inactivation in eutherian mammals has been thought to be tightly controlled, as expected from a mechanism that compensates for the different dosage of X-borne genes in XX females and XY males. However, many X genes escape inactivation in humans, inactivation of the X in marsupials is partial, and the unrelated sex chromosomes of monotreme mammals have incomplete and gene-specific inactivation of X-linked genes. The bird ZW sex chromosome system represents a third independently evolved amniote sex chromosome system with dosage compensation, albeit partial and gene-specific, via an unknown mechanism (i.e. upregulation of the single Z in females, down regulation of one or both Zs in males, or a combination). We used RNA-fluorescent in situ hybridization (RNA-FISH) to demonstrate, on individual fibroblast cells, inactivation of 11 genes on the chicken Z and 28 genes on the X chromosomes of platypus. Each gene displayed a reproducible frequency of 1Z/1X-active and 2Z/2X-active cells in the homogametic sex. Our results indicate that the probability of inactivation is controlled on a gene-by-gene basis (or small domains) on the chicken Z and platypus X chromosomes. This regulatory mechanism must have been exapted independently to the non-homologous sex chromosomes in birds and mammals in response to an over-expressed Z or X in the homogametic sex, highlighting the universal importance that (at least partial) silencing plays in the evolution on amniote dosage compensation and, therefore, the differentiation of sex chromosomes.

  11. The Social Cost of Stochastic and Irreversible Climate Change

    NASA Astrophysics Data System (ADS)

    Cai, Y.; Judd, K. L.; Lontzek, T.

    2013-12-01

    Many scientists are worried about climate change triggering abrupt and irreversible events leading to significant and long-lasting damages. For example, a rapid release of methane from permafrost may lead to amplified global warming, and global warming may increase the frequency and severity of heavy rainfall or typhoon, destroying large cities and killing numerous people. Some elements of the climate system which might exhibit such a triggering effect are called tipping elements. There is great uncertainty about the impact of anthropogenic carbon and tipping elements on future economic wellbeing. Any rational policy choice must consider the great uncertainty about the magnitude and timing of global warming's impact on economic productivity. While the likelihood of tipping points may be a function of contemporaneous temperature, their effects are long lasting and might be independent of future temperatures. It is assumed that some of these tipping points might occur even in this century, but also that their duration and post-tipping impact are uncertain. A faithful representation of the possibility of tipping points for the calculation of social cost of carbon would require a fully stochastic formulation of irreversibility, and accounting for the deep layer of uncertainties regarding the duration of the tipping process and also its economic impact. We use DSICE, a DSGE extension of the DICE2007 model of William Nordhaus, which incorporates beliefs about the uncertain economic impact of possible climate tipping events and uses empirically plausible parameterizations of Epstein-Zin preferences to represent attitudes towards risk. We find that the uncertainty associated with anthropogenic climate change imply carbon taxes much higher than implied by deterministic models. This analysis indicates that the absence of uncertainty in DICE2007 and similar IAM models may result in substantial understatement of the potential benefits of policies to reduce GHG emissions.

  12. Structural Basis for Reversible and Irreversible Inhibition of Human Cathepsin L by their Respective dipeptidyl glyoxal and diazomethylketone Inhibitors

    SciTech Connect

    R Shenoy; J Sivaraman

    2011-12-31

    Cathepsin L plays a key role in many pathophysiological conditions including rheumatoid arthritis, tumor invasion and metastasis, bone resorption and remodeling. Here we report the crystal structures of two analogous dipeptidyl inhibitor complexes which inhibit human cathepsin L in reversible and irreversible modes, respectively. To-date, there are no crystal structure reports of complexes of proteases with their glyoxal inhibitors or complexes of cathepsin L and their diazomethylketone inhibitors. These two inhibitors - inhibitor 1, an {alpha}-keto-{beta}-aldehyde and inhibitor 2, a diazomethylketone, have different groups in the S1 subsite. Inhibitor 1 [Z-Phe-Tyr (OBut)-COCHO], with a Ki of 0.6 nM, is the most potent, reversible, synthetic peptidyl inhibitor of cathepsin L reported to-date. The structure of the inhibitor 1 complex was refined up to 2.2 {angstrom} resolution. The structure of the complex of the inhibitor 2 [Z-Phe-Tyr (t-Bu)-diazomethylketone], an irreversible inhibitor that can inactivate cathepsin L at {micro}M concentrations, was refined up to 1.76 {angstrom} resolution. These two inhibitors have substrate-like interactions with the active site cysteine (Cys25). Inhibitor 1 forms a tetrahedral hemithioacetal adduct, whereas the inhibitor 2 forms a thioester with Cys25. The inhibitor 1 {beta}-aldehyde group is shown to make a hydrogen bond with catalytic His163, whereas the ketone carbonyl oxygen of the inhibitor 2 interacts with the oxyanion hole. tert-Butyl groups of both inhibitors are found to make several non-polar contacts with S' subsite residues of cathepsin L. These studies, combined with other complex structures of cathepsin L, reveal the structural basis for their potency and selectivity.

  13. Cinnamic acid 4-hydroxylase mechanism-based inactivation by psoralen derivatives: cloning and characterization of a C4H from a psoralen producing plant-Ruta graveolens-exhibiting low sensitivity to psoralen inactivation.

    PubMed

    Gravot, Antoine; Larbat, Romain; Hehn, Alain; Lièvre, Karine; Gontier, Eric; Goergen, Jean Louis; Bourgaud, Frédéric

    2004-02-01

    Cinnamate 4-hydroxylase (C4H, EC 1.14.13.11) complete cDNA was cloned from the leaves of Ruta graveolens, a psoralen producing plant. The recombinant enzyme (classified CYP73A32) was expressed in Saccharomyces cerevisiae. Mechanism-based inactivation was investigated using various psoralen derivatives. Only psoralen and 8-methoxypsoralen were found to inactivate C4H. The inactivation was dependent on the presence of NADPH, time of pre-incubation, and inhibitor concentration. Inactivation stoichiometry was 0.9 (+/-0.2) for CYP73A1 and 1.1 (+/-0.2) for CYP73A32. SDS-PAGE analysis demonstrated that [3H]psoralen was irreversibly bound to the C4H apoprotein. K(i) and k(inact) for psoralen and 8-methoxypsoralen inactivation on the two C4H revealed a lower sensitivity for CYP73A32 compared to CYP73A1. Inactivation kinetics were also determined for CYP73A10, a C4H from another furocoumarin-producing plant, Petroselinum crispum. This enzyme was found to behave like CYP73A32, with a weak sensitivity to psoralen and 8-MOP inactivation. Cinnamic acid hydroxylation is a key step in the biosynthesis of phenylpropanoid compounds, psoralen derivatives included. Our results suggest a possible evolution of R. graveolens and P. crispum C4H that might tolerate substantial levels of psoralen derivatives in the cytoplasmic compartment without a depletive effect on C4H and the general phenylpropanoid metabolism.

  14. Inactivation and injury assessment of Escherichia coli during solar and photocatalytic disinfection in LDPE bags.

    PubMed

    Dunlop, P S M; Ciavola, M; Rizzo, L; Byrne, J A

    2011-11-01

    Solar disinfection (SODIS) of Escherichia coli suspensions in low-density polyethylene bag reactors was investigated as a low-cost disinfection method suitable for application in developing countries. The efficiency of a range of SODIS reactor configurations was examined (single skin (SS), double skin, black-backed single skin, silver-backed single skin (SBSS) and composite-backed single skin) using E. coli suspended in model and real surface water. Titanium dioxide was added to the reactors to improve the efficiency of the SODIS process. The effect of turbidity was also assessed. In addition to viable counts, E. coli injury was characterised through spread-plate analysis using selective and non-selective media. The optimal reactor configuration was determined to be the SBSS bag (t(50)=9.0min) demonstrating the importance of UVA photons, as opposed to infrared in the SODIS disinfection mechanism. Complete inactivation (6.5-log) was achieved in the presence of turbidity (50NTU) using the SBSS bag within 180min simulated solar exposure. The addition of titanium dioxide (0.025gL(-1)) significantly enhanced E. coli inactivation in the SS reactor, with 6-log inactivation observed within 90min simulated solar exposure. During the early stages of both SODIS and photocatalytic disinfection, injured E. coli were detected; however, irreversible injury was caused and re-growth was not observed. Experiments under solar conditions were undertaken with total inactivation (6.5-log) observed in the SS reactor within 240min, incomplete inactivation (4-log) was observed in SODIS bottles exposed to the same solar conditions.

  15. MPLEx: a method for simultaneous pathogen inactivation and extraction of samples for multi-omics profiling

    SciTech Connect

    Burnum-Johnson, Kristin E.; Kyle, Jennifer E.; Eisfeld, Amie J.; Casey, Cameron P.; Stratton, Kelly G.; Gonzalez, Juan F.; Habyarimana, Fabien; Negretti, Nicholas M.; Sims, Amy C.; Chauhan, Sadhana; Thackray, Larissa B.; Halfmann, Peter J.; Walters, Kevin B.; Kim, Young-Mo; Zink, Erika M.; Nicora, Carrie D.; Weitz, Karl K.; Webb-Robertson, Bobbie-Jo M.; Nakayasu, Ernesto S.; Ahmer, Brian; Konkel, Michael E.; Motin, Vladimir; Baric, Ralph S.; Diamond, Michael S.; Kawaoka, Yoshihiro; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.

    2017-01-01

    The continued emergence and spread of infectious agents is of increasing concern due to increased population growth and the associated increased livestock production to meet food demands, increased urbanization and land-use changes, and greater travel. A systems biology approach to infectious disease research can significantly advance our understanding of host-pathogen relationships and facilitate the development of new therapies and vaccines. Molecular characterization of infectious samples outside of appropriate biosafety containment can only take place subsequent to pathogen inactivation. Herein, we describe a modified Folch extraction using chloroform/methanol that facilitates the molecular characterization of infectious samples by enabling simultaneous pathogen inactivation and extraction of proteins, metabolites, and lipids for subsequent mass spectrometry-based multi-omics measurements. This metabolite, protein and lipid extraction (MPLEx) method resulted in complete inactivation of bacterial and viral pathogens with exposed lipid membranes, including Yersinia pestis, Salmonella Typhimurium, and Campylobacter jejuni in pure culture, and Yersinia pestis, Campylobacter jejuni, West Nile, MERS-CoV, Ebola, and influenza H7N9 viruses in infection studies. Partial inactivation was observed for pathogens without exposed lipid membranes including 99.99% inactivation of community-associated methicillin-resistant Staphylococcus aureus, 99.6% and >99% inactivation of Clostridium difficile spores and vegetative cells, respectively, and 50% inactivation of adenovirus type 5. To demonstrate that MPLEx yields biomaterial of sufficient quality for subsequent multi-omics analyses, we highlight select proteomics, metabolomics and lipidomics data from human epithelial lung cells infected with wild-type and mutant forms of influenza H7N9. We believe that MPLEx will facilitate systems biology studies of infectious samples by enabling simultaneous pathogen inactivation and multi

  16. Performance of an irreversible quantum Carnot engine with spin 1/2

    NASA Astrophysics Data System (ADS)

    Wu, Feng; Chen, Lingen; Wu, Shuang; Sun, Fengrui; Wu, Chih

    2006-06-01

    The purpose of this paper is to investigate the effect of quantum properties of the working medium on the performance of an irreversible Carnot cycle with spin 1/2. The optimal relationship between the dimensionless power output P* versus the efficiency η for the irreversible quantum Carnot engine with heat leakage and other irreversible losses is derived. Especially, the performances of the engine at low temperature limit and at high temperature limit are discussed.

  17. [Oxidative inactivation of angiotensin-converting enzyme].

    PubMed

    Sakharov, I Iu; Dukhanina, E A; Puchnina, E A; Danilov, S M; Muzykantov, V R

    1991-01-01

    Hydrogen peroxide inactivates the purified human angiotensin-converting enzyme (ACE) in vitro; the inactivating effect of H2O2 is eliminated by an addition of catalase. The lung and kidney ACE are equally sensitive to the effect of hydrogen peroxide. After addition of oxidants (H2O2 alone or H2O2 + ascorbate or H2O2 + Fe2+ mixtures) to the membranes or homogenates of the lung, the inactivation of membrane-bound ACE is far less pronounced despite the large-scale accumulation of lipid peroxidation products. The marked inactivation of ACE in the membrane fraction (up to 55% of original activity) was observed during ACE incubation with a glucose:glucose oxidase:Fe2+ mixture. Presumably the oxidative potential of H2O2 in tissues in consumed, predominantly, for the oxidation of other components of the membrane (e.g., lipids) rather than for ACE inactivation.

  18. Photodynamic inactivation of mammalian viruses and bacteriophages.

    PubMed

    Costa, Liliana; Faustino, Maria Amparo F; Neves, Maria Graça P M S; Cunha, Angela; Almeida, Adelaide

    2012-07-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  19. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    PubMed Central

    Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

    2012-01-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

  20. Susceptibility of the early Earth to irreversible glaciation caused by carbon dioxide clouds.

    PubMed

    Caldeira, K; Kasting, J F

    1992-09-17

    Simple energy-balance climate models of the Budyko/Sellers type predict that a small (2-5%) decrease in solar output could result in runaway glaciation on the Earth. But solar fluxes 25-30% lower early in the Earth's history apparently did not lead to this result. One currently favoured explanation is that high partial pressures of carbon dioxide, caused by higher volcanic outgassing rates and/or slower rates of silicate weathering, created a large enough greenhouse effect to keep the planet warm. This does not resolve the problem of climate stability, however, because as we argue here, the oceans can freeze much more quickly than CO2 can accumulate in the atmosphere. Had such a transient global glaciation occurred in the distant past when solar luminosity was low, it might have been irreversible because of the formation of highly reflective CO2 clouds, similar to those encountered in climate simulations of early Mars. Our simulations of the early Earth, incorporating the possible formation of such clouds, suggest that the Earth might not be habitable today had it not been warm during the first part of its history.

  1. Irreversible binding of an anticancer compound (BI-94) to plasma proteins

    PubMed Central

    Gautam, Nagsen; Thakare, Rhishikesh; Rana, Sandeep; Natarajan, Amarnath; Alnouti, Yazen

    2015-01-01

    1. We investigated the mechanisms responsible for the in vivo instability of a benzofurazan compound BI-94 (NSC228148) with potent anti-cancer activity. 2. BI-94 was stable in MeOH, water, and in various buffers at pHs 2.5–5, regardless of the buffer composition. In contrast, BI-94 was unstable in NaOH and at pHs 7–9, regardless of the buffer composition. BI-94 disappeared immediately after spiking into mice, rat, monkey, and human plasma. BI-94 stability in plasma can be only partially restored by acidifying it, which indicated other mechanisms in addition to pH for BI-94 instability in plasma. 3. BI-94 formed adducts with the trapping agents, glutathione (GSH) and N-acetylcysteine (NAC), in vivo and in vitro via nucleophilic aromatic substitution reaction. The kinetics of adduct formation showed that neutral or physiological pHs enhanced and accelerated GSH and NAC adduct formation with BI-94, whereas acidic pHs prevented it. Therefore, physiological pHs not only altered BI-94 chemical stability but also enhanced adduct formation with endogenous nucleophiles. In addition, adduct formation with human serum albumin-peptide 3 (HSA-T3) at the Cys34 position was demonstrated. 4. In conclusion, BI-94 was unstable at physiological conditions due to chemical instability and irreversible binding to plasma proteins. PMID:25869245

  2. Percutaneous Irreversible Electroporation Lung Ablation: Preliminary Results in a Porcine Model

    SciTech Connect

    Deodhar, Ajita; Monette, Sebastien; Single, Gordon W.; Hamilton, William C.; Thornton, Raymond H.; Sofocleous, Constantinos T.; Maybody, Majid; Solomon, Stephen B.

    2011-12-15

    Objective: Irreversible electroporation (IRE) uses direct electrical pulses to create permanent 'pores' in cell membranes to cause cell death. In contrast to conventional modalities, IRE has a nonthermal mechanism of action. Our objective was to study the histopathological and imaging features of IRE in normal swine lung. Materials and Methods: Eleven female swine were studied for hyperacute (8 h), acute (24 h), subacute (96 h), and chronic (3 week) effects of IRE ablation in lung. Paired unipolar IRE applicators were placed under computed tomography (CT) guidance. Some applicators were deliberately positioned near bronchovascular structures. IRE pulse delivery was synchronized with the cardiac rhythm only when ablation was performed within 2 cm of the heart. Contrast-enhanced CT scan was performed immediately before and after IRE and at 1 and 3 weeks after IRE ablation. Representative tissue was stained with hematoxylin and eosin for histopathology. Results: Twenty-five ablations were created: ten hyperacute, four acute, and three subacute ablations showed alveolar edema and necrosis with necrosis of bronchial, bronchiolar, and vascular epithelium. Bronchovascular architecture was maintained. Chronic ablations showed bronchiolitis obliterans and alveolar interstitial fibrosis. Immediate post-procedure CT images showed linear or patchy density along the applicator tract. At 1 week, there was consolidation that resolved partially or completely by 3 weeks. Pneumothorax requiring chest tube developed in two animals; no significant cardiac arrhythmias were noted. Conclusion: Our preliminary porcine study demonstrates the nonthermal and extracellular matrix sparing mechanism of action of IRE. IRE is a potential alternative to thermal ablative modalities.

  3. Histological and Finite Element Analysis of Cell Death due to Irreversible Electroporation

    PubMed Central

    Long, G.; Bakos, G.; Shires, P. K.; Gritter, L.; Crissman, J. W.; Harris, J. L.; Clymer, J. W.

    2014-01-01

    Irreversible electroporation (IRE) has been shown to be an effective method of killing cells locally. In contrast to radiofrequency ablation, the mechanism by which cells are thought to die via IRE is the creation of pores in cell membranes, without substantial increase in tissue temperature. To determine the degree to which cell death is non-thermal, we evaluated IRE in porcine hepatocytes in vivo. Using pulse widths of 10μs, bursts of 3 kV square-wave pulses were applied through a custom probe to the liver of an anesthetized pig. Affected tissue was evaluated histologically via stainings of hematoxylin & eosin (H&E), nitroblue tetrazolium (NBT) to monitor cell respiration and TUNEL to gauge apoptosis. Temperature was measured during the application of electroporation, and heat transfer was modeled via finite element analysis. Cell death was calculated via Arrhenius kinetics. Four distinct zones were observed within the ring return electrode; heat-fixed tissue, coagulation, necrotic, and viable. The Arrhenius damage integral estimated complete cell death only in the first zone, where the temperature exceeded 70°C, and partial or no cell death in the other zones, where maximum temperature was approximately 45°C. Except for a limited area near the electrode tip, cell death in IRE is predominantly due to a non-thermal mechanism. PMID:24000980

  4. Irreversible and reversible reactive chromatography: analytical solutions and moment analysis for rectangular pulse injections.

    PubMed

    Bibi, Sameena; Qamar, Shamsul; Seidel-Morgenstern, Andreas

    2015-03-13

    This work is concerned with the analysis of models for linear reactive chromatography describing irreversible A→B and reversible A↔B reactions. In contrast to previously published results rectangular reactant pulses are injected into initially empty or pre-equilibrated columns assuming both Dirichlet and Danckwerts boundary conditions. The models consist of two partial differential equations, accounting for convection, longitudinal dispersion and first order chemical reactions. Due to the effect of involved mechanisms on solute transport, analytical and numerical solutions of the models could be helpful to understand, design and optimize chromatographic reactors. The Laplace transformation is applied to solve the model equations analytically for linear adsorption isotherms. Statistical temporal moments are derived from solutions in the Laplace domain. Analytical results are compared with numerical predictions generated using a high-resolution finite volume scheme for two sets of boundary conditions. Several case studies are carried out to analyze reactive liquid chromatographic processes for a wide range of mass transfer and reaction kinetics. Good agreements in the results validate the correctness of the analytical solutions and accuracy of the proposed numerical algorithm.

  5. Synthesis and biochemical studies of 7 alpha-substituted androsta-1,4-diene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase.

    PubMed

    Ebrahimian, S; Chen, H H; Brueggemeier, R W

    1993-09-01

    Several 7 alpha-thiosubstituted derivatives of androstenedione have demonstrated effective inhibition of aromatase, the cytochrome P450 enzyme complex responsible for the biosynthesis of estrogens. Introduction of an additional double bond in the A ring resulted in 7 alpha-(4'-amino)phenylthioandrosta-1,4-diene-3,17-dione (7 alpha-APTADD), a potent inhibitor that inactivated aromatase by an enzyme-catalyzed process. Additional 7 alpha-thiosubstituted androsta-1,4-diene-3,17-dione derivatives were designed to further examine enzyme-catalyzed inactivation. Two halogenated and one unsubstituted 7 alpha-phenylthioandrosta-1,4-diene-3,17-diones were synthesized via an acid-catalyzed conjugate Michael addition of substituted thiophenols with androsta-1,4,6-triene-3,17-dione. Two 7 alpha-naphthylthioandrosta-1,4-diene-3,17-diones were synthesized via either acid-catalyzed or based-catalyzed conjugate Michael addition of substituted thionaphthols with androsta-1,4,6-triene-3,17-dione. These agents were evaluated for aromatase inhibitory activity in the human placental microsomal preparation. Under initial velocity assay conditions of low product formation, the inhibitors demonstrated potent inhibition of aromatase, with apparent Ki's ranging from 12 to 27 nM. Furthermore, these compounds produced time-dependent, first-order inactivation of aromatase in the presence of NADPH, whereas no aromatase inactivation was observed in the absence of NADPH. This enzyme-activated irreversible inhibition, also referred to as mechanism-based inhibition, can be prevented by the substrate androstenedione. Thus, the apparent Ki values for these inhibitors are consistent with earlier studies on 7 alpha-substituted competitive inhibitors that indicate bulky substituents can be accommodated at the 7 alpha-position.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Resistance to PARP inhibitors by SLFN11 inactivation can be overcome by ATR inhibition

    PubMed Central

    Murai, Junko; Feng, Ying; Yu, Guoying K.; Ru, Yuanbin; Tang, Sai-Wen; Shen, Yuqiao; Pommier, Yves

    2016-01-01

    Poly(ADP-ribose) polymerase inhibitors (PARPIs) kill cancer cells by trapping PARP1 and PARP2. Talazoparib, the most potent PARPI inhibitor (PARPI), exhibits remarkable selectivity among the NCI-60 cancer cell lines beyond BRCA inactivation. Our genomic analyses reveal high correlation between response to talazoparib and Schlafen 11 (SLFN11) expression. Causality was established in four isogenic SLFN11-positive and -negative cell lines and extended to olaparib. Response to the talazoparib-temozolomide combination was also driven by SLFN11 and validated in 36 small cell lung cancer cell lines, and in xenograft models. Resistance in SLFN11-deficient cells was caused neither by impaired drug penetration nor by activation of homologous recombination. Rather, SLFN11 induced irreversible and lethal replication inhibition, which was independent of ATR-mediated S-phase checkpoint. The resistance to PARPIs by SLFN11 inactivation was overcome by ATR inhibition, mechanistically because SLFN11-deficient cells solely rely on ATR activation for their survival under PARPI treatment. Our study reveals that SLFN11 inactivation, which is common (~45%) in cancer cells, is a novel and dominant resistance determinant to PARPIs. PMID:27708213

  7. DIDS modifies the conductance, gating, and inactivation mechanisms of the cardiac ryanodine receptor.

    PubMed Central

    Hill, Adam Parker; Sitsapesan, Rebecca

    2002-01-01

    The effects of the covalent modifier of amino groups, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) on the single-channel properties of purified sheep cardiac ryanodine receptors (RyR) incorporated into planar phospholipid bilayers were investigated. DIDS increased single-channel conductance and open probability (P(o)) and induced unique modifications to the voltage-dependence of gating. The effects of DIDS on conduction and gating were irreversible within the time scale of the experiments, and both effects were dependent on the permeant ion. DIDS induced a greater increase in conductance with Ca(2+) (20%) compared with K(+) (8%) as the permeant ion. After modification by DIDS, all channels could be rapidly inactivated in a voltage-dependent manner. The open probability of the DIDS-modified channel decreased with increasing positive or negative transmembrane potentials; however, inactivation was only observed at negative potentials. Our results demonstrate that inactivation of RyR channels is dependent on the ligand activating the channel, and this will have consequences for the control and termination of sarcoplasmic reticulum Ca(2+) release in cardiac cells. PMID:12023226

  8. Process boundaries of irreversible scCO2 -assisted phase separation in biphasic whole-cell biocatalysis.

    PubMed

    Brandenbusch, Christoph; Glonke, Sebastian; Collins, Jonathan; Hoffrogge, Raimund; Grunwald, Klaudia; Bühler, Bruno; Schmid, Andreas; Sadowski, Gabriele

    2015-11-01

    The formation of stable emulsions in biphasic biotransformations catalyzed by microbial cells turned out to be a major hurdle for industrial implementation. Recently, a cost-effective and efficient downstream processing approach, using supercritical carbon dioxide (scCO2 ) for both irreversible emulsion destabilization (enabling complete phase separation within minutes of emulsion treatment) and product purification via extraction has been proposed by Brandenbusch et al. (2010). One of the key factors for a further development and scale-up of the approach is the understanding of the mechanism underlying scCO2 -assisted phase separation. A systematic approach was applied within this work to investigate the various factors influencing phase separation during scCO2 treatment (that is pressure, exposure of the cells to CO2 , and changes of cell surface properties). It was shown that cell toxification and cell disrupture are not responsible for emulsion destabilization. Proteins from the aqueous phase partially adsorb to cells present at the aqueous-organic interface, causing hydrophobic cell surface characteristics, and thus contribute to emulsion stabilization. By investigating the change in cell-surface hydrophobicity of these cells during CO2 treatment, it was found that a combination of catastrophic phase inversion and desorption of proteins from the cell surface is responsible for irreversible scCO2 mediated phase separation. These findings are essential for the definition of process windows for scCO2 -assisted phase separation in biphasic whole-cell biocatalysis.

  9. Large field-induced irreversibility in Ni-Mn based Heusler shape-memory alloys: A pulsed magnetic field study

    NASA Astrophysics Data System (ADS)

    Nayak, A. K.; Mejia, C. Salazar; D'Souza, S. W.; Chadov, S.; Skourski, Y.; Felser, C.; Nicklas, M.

    2014-12-01

    We present a pulsed magnetic field study on the magnetic and magnetostriction properties of Ni-Mn-Z (Z =In , Sn, and Sb) based Heusler shape-memory alloys. These materials generally display a field-induced magnetostructural transition that could lead to an irreversible phase transition, when measured near the martensitic transition temperature. Here, we show that independently of the transition temperature, the critical field for the phase transition sensitively depends on the main-group element in the sample. Irrespective of their compositions, all samples display a magnetization of around 2 μB/f .u . in the martensite phase and about 6 μB/f .u . in the cubic austenite phase. Our magnetic and magnetostriction measurements at low temperatures exhibit a partial or complete arrest of the high-field austenite phase below the reverse martensitic transition. This results in a large irreversibility with a hysteresis width as high as 24 T. We introduce a theoretical model to discuss the experimental results.

  10. In Situ TEM Study of Reversible and Irreversible Electroforming in Pt/Ti:NiO/Pt Heterostructures

    SciTech Connect

    D'Aquila, Kenneth; Liu, Yuzi; Iddir, Hakim; Petford-Long, Amanda K.

    2015-05-01

    Experimental verification of the microscopic origin of resistance switching in metal/oxide/metal heterostructures is needed for applications in non-volatile memory and neuromorphic computing. Numerous reports suggest that resistance switching in NiO is caused by local reduction of the oxide layer into nanoscale conducting filaments, but few reports have shown experimental evidence correlating electroforming with site-specific changes in composition. We have investigated the mechanisms of reversible and irreversible electroforming in 250–500 nm wide pillars patterned from a single Ta/Ti/Pt/Ti-doped NiO/Pt/Ta heterostructure and have shown that these can coexist within a single sample. We performed in situ transmission electron microscopy (TEM) electroform- ing and switching on each pillar to correlate the local electron transport behavior with microstructure and composition in each pillar. DFT calculations fitted to electron energy loss spectroscopy data showed that the Ti-doped NiO layer is partially reduced after reversible electroforming, with the formation of oxygen vacancies ordered into lines in the <110> direction. However, under the same probing conditions, adjacent pillars show irreversible electroforming caused by electromigration of metallic Ta to form a single bridge across the oxide layer. We propose that the different electroforming behaviors are related to microstructural variations across the sample and may lead to switching variability.

  11. Voltage sensor inactivation in potassium channels.

    PubMed

    Bähring, Robert; Barghaan, Jan; Westermeier, Regina; Wollberg, Jessica

    2012-01-01

    In voltage-gated potassium (Kv) channels membrane depolarization causes movement of a voltage sensor domain. This conformational change of the protein is transmitted to the pore domain and eventually leads to pore opening. However, the voltage sensor domain may interact with two distinct gates in the pore domain: the activation gate (A-gate), involving the cytoplasmic S6 bundle crossing, and the pore gate (P-gate), located externally in the selectivity filter. How the voltage sensor moves and how tightly it interacts with these two gates on its way to adopt a relaxed conformation when the membrane is depolarized may critically determine the mode of Kv channel inactivation. In certain Kv channels, voltage sensor movement leads to a tight interaction with the P-gate, which may cause conformational changes that render the selectivity filter non-conductive ("P/C-type inactivation"). Other Kv channels may preferably undergo inactivation from pre-open closed-states during voltage sensor movement, because the voltage sensor temporarily uncouples from the A-gate. For this behavior, known as "preferential" closed-state inactivation, we introduce the term "A/C-type inactivation". Mechanistically, P/C- and A/C-type inactivation represent two forms of "voltage sensor inactivation."

  12. Inactivation of ribulosebisphosphate carboxylase/oxygenase from Rhodospirillum rubrum and spinach with the new affinity label 2-bromo-1,5-dihydroxy-3-pentanone 1,5-bisphosphate

    SciTech Connect

    Donnelly, M.I.; Hartman, F.C.

    1981-11-16

    In an attempt to identify the active-site base believed to initiate catalysis by ribulosebisphosphate carboxylase, we have synthesized 2-bromo-1, 5-dihydroxy-3-pentanone 1,5-bisphosphate, a reactive analogue of a postulated intermediate of carboxylation. Although highly unstable, this compound can be shown to inactivate the carboxylases from both Rhodospirillum rubrum and spinach rapidly and irreversibly. Inactivation follows pseudo first-order kinetics, shows rate saturation and is greatly reduced by saturating amounts of the competitive inhibitor, 2-carboxyribitol 1,5-bisphosphate. The incorporation of reagent, quantified by reducing the modified carboxylases with (/sup 3/H)NaBH/sub 4/, shows that inactivation results from the modification of approximately one residue per catalytic subunit of the Rhodospirillum rubrum enzyme and less than one residue per protomeric unit of the spinach enzyme.

  13. Scaling Law for Irreversible Entropy Production in Critical Systems

    PubMed Central

    Hoang, Danh-Tai; Prasanna Venkatesh, B.; Han, Seungju; Jo, Junghyo; Watanabe, Gentaro; Choi, Mahn-Soo

    2016-01-01

    We examine the Jarzynski equality for a quenching process across the critical point of second-order phase transitions, where absolute irreversibility and the effect of finite-sampling of the initial equilibrium distribution arise in a single setup with equal significance. We consider the Ising model as a prototypical example for spontaneous symmetry breaking and take into account the finite sampling issue by introducing a tolerance parameter. The initially ordered spins become disordered by quenching the ferromagnetic coupling constant. For a sudden quench, the deviation from the Jarzynski equality evaluated from the ideal ensemble average could, in principle, depend on the reduced coupling constant ε0 of the initial state and the system size L. We find that, instead of depending on ε0 and L separately, this deviation exhibits a scaling behavior through a universal combination of ε0 and L for a given tolerance parameter, inherited from the critical scaling laws of second-order phase transitions. A similar scaling law can be obtained for the finite-speed quench as well within the Kibble-Zurek mechanism. PMID:27277558

  14. Intrinsic randomness and intrinsic irreversibility in classical dynamical systems

    PubMed Central

    Courbage, M.; Prigogine, I.

    1983-01-01

    We continue our previous work on dynamic “intrinsically random” systems for which we can derive dissipative Markov processes through a one-to-one change of representation. For these systems, the unitary group of evolution can be transformed in this way into two distinct Markov processes leading to equilibrium for either t→ + ∞ or t→ - ∞. To lift the degeneracy, we first formulate the second principle as a selection rule that is meaningful in intrinsically random systems. For these systems, this excludes a set of unrealizable states. As a result of this exclusion, permitted initial conditions correspond to a set of states that is not invariant through velocity inversion. In this way, the time-reversal symmetry of dynamics is broken and these systems acquire a new feature we may call “intrinsic irreversibility.” The set of admitted initial conditions can be characterized by an entropy displaying the amount of information necessary for their preparation. The initial conditions selected by the second law correspond to a finite amount of information, while the initial conditions that are rejected correspond to an infinite amount of information and are therefore “impossible.” We believe that our formulation permits a microscopic formulation of the second law of thermodynamics for well-defined classes of dynamical systems. PMID:16578774

  15. Irreversible Entropy Production in Two-Phase Mixing Layers

    NASA Technical Reports Server (NTRS)

    Okongo, Nora

    2003-01-01

    This report presents a study of dissipation (irreversible production of entropy) in three-dimensional, temporal mixing layers laden with evaporating liquid drops. The purpose of the study is to examine the effects of evaporating drops on the development of turbulent features in flows. Direct numerical simulations were performed to analyze transitional states of three mixing layers: one without drops, and two that included drops at different initial mass loadings. Without drops, the dissipation is essentially due to viscous effects. It was found that in the presence of drops, the largest contribution to dissipation was made by heating and evaporation of the drops, and that at large length scales, this contribution is positive (signifying that the drops reduce turbulence), while at small scales, this contribution is negative (the drops increase turbulence). The second largest contribution to dissipation was found to be associated with the chemical potential, which leads to an increase in turbulence at large scales and a decrease in turbulence at small scales. The next smaller contribution was found to be that of viscosity. The fact that viscosity effects are only third in order of magnitude in the dissipation is in sharp contrast to the situation for the mixing layer without the drops. The next smaller contribution - that of the drag and momentum of the vapor from the drops - was found to be negative at lower mass loading but to become positive at higher mass loading.

  16. The nineteenth century conflict between mechanism and irreversibility

    NASA Astrophysics Data System (ADS)

    van Strien, Marij

    2013-08-01

    The reversibility problem (better known as the reversibility objection) is usually taken to be an internal problem in the kinetic theory of gases, namely the problem of how to account for the second law of thermodynamics within this theory. Historically, it is seen as an objection that was raised against Boltzmann's kinetic theory of gases, which led Boltzmann to a statistical approach to the kinetic theory, culminating in the development of statistical mechanics. In this paper, I show that in the late nineteenth century, the reversibility problem had a much broader significance-it was widely discussed and certainly not only as an objection to Boltzmann's kinetic theory of gases. In this period, there was a conflict between mechanism and irreversibility in physics which was tied up with central issues in philosophy of science such as materialism, empiricism and the need for mechanistic foundations of physical theories, as well as with concerns about the heat death of the universe. I discuss how this conflict was handled by the major physicists of the period, such as Maxwell, Kelvin, Duhem, Poincaré, Mach and Planck, as well as by a number of lesser-known authors.

  17. General performance characteristics of an irreversible ferromagnetic Stirling refrigeration cycle

    NASA Astrophysics Data System (ADS)

    Lin, G.; Tegus, O.; Zhang, L.; Brück, E.

    2004-02-01

    A new magnetic-refrigeration-cycle model using ferromagnetic materials as a cyclic working substance is set up, in which finite-rate heat transfer, heat leak and regeneration time are taken into account. On the basis of the thermodynamic properties of a ferromagnetic material, the general performance characteristics of the ferromagnetic Stirling refrigeration cycle are investigated and the effects of some key irreversibilities on the performance of the cycle are revealed. By using the optimal-control theory, the optimal relation between the coefficient of performance and the cooling rate is derived and some important performance bounds, e.g., the maximum cooling rate, the maximum coefficient of performance, are determined. Moreover, the optimal operating regions for cooling rate, coefficient of performance and the optimal operating temperatures of a cyclic working substance in the two heat-transfer processes are obtained. Furthermore, the influences of magnetization and magnetic field on the performance characteristics of the cycle are discussed. The results obtained here have general significance and can be deduced to the related ones of the Stirling refrigeration cycle using paramagnetic salt as a cyclic working substance.

  18. Percolation of heteronuclear dimers irreversibly deposited on square lattices

    NASA Astrophysics Data System (ADS)

    Gimenez, M. C.; Ramirez-Pastor, A. J.

    2016-09-01

    The percolation problem of irreversibly deposited heteronuclear dimers on square lattices is studied. A dimer is composed of two segments, and it occupies two adjacent adsorption sites. Each segment can be either a conductive segment (segment type A ) or a nonconductive segment (segment type B ). Three types of dimers are considered: A A , B B , and A B . The connectivity analysis is carried out by accounting only for the conductive segments (segments type A ). The model offers a simplified representation of the problem of percolation of defective (nonideal) particles, where the presence of defects in the system is simulated by introducing a mixture of conductive and nonconductive segments. Different cases were investigated, according to the sequence of deposition of the particles, the types of dimers involved in the process, and the degree of alignment of the deposited objects. By means of numerical simulations and finite-size scaling analysis, the complete phase diagram separating a percolating from a nonpercolating region was determined for each case. Finally, the consistency of our results was examined by comparing with previous data in the literature for linear k -mers (particles occupying k adjacent sites) with defects.

  19. Use of irreversible electroporation in unresectable pancreatic cancer

    PubMed Central

    2015-01-01

    Irreversible electroporation is a non-thermal injury ablative modality that has been in clinical use since 2008 in the treatment of locally advanced soft tissue tumors. It has been reported to be utilized intraoperatively, laparoscopically or percutaneously. The method of action of IRE relies on a high voltage (maximum 3,000 volts) small microsecond pulse lengths (70 to 90 microseconds) to induce cell membrane porosity which leads to slow/protracted cell death over time. One of the largest unmet needs in oncology that IRE has been utilized is in locally advanced (stage III) pancreatic cancer. Recent studies have demonstrated the safety and palliation with encouraging improvement in overall survival. Its inherent limitation still remains tissue heterogeneity and the unique settings based on tumor histology and prior induction therapy. There remains a high technical demand of the end-user and the more extensive knowledge transfer which makes the learning curve longer in order to achieve appropriate and safe utilization. PMID:26151062

  20. Irreversible electroporation of locally advanced pancreatic neck/body adenocarcinoma

    PubMed Central

    2015-01-01

    Objective Irreversible electroporation (IRE) of locally advanced pancreatic adenocarcinoma of the neck has been used to palliate appropriate stage 3 pancreatic cancers without evidence of metastasis and who have undergone appropriate induction therapy. Currently there has not been a standardized reported technique for pancreatic mid-body tumors for patient selection and intra-operative technique. Patients Subjects are patients with locally advanced pancreatic adenocarcinoma of the body/neck who have undergone appropriate induction chemotherapy for a reasonable duration. Main outcome measures Technique of open IRE of locally advanced pancreatic adenocarcinoma of the neck/body is described, with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open IRE of the pancreatic neck/body with bracketing of the celiac axis and superior mesenteric artery with continuous intraoperative ultrasound imaging and consideration of intraoperative navigational system is described. Conclusions IRE of locally advanced pancreatic adenocarcinoma of the body/neck is feasible for appropriate patients with locally advanced unresectable pancreatic cancer. PMID:26029461

  1. Percolation of heteronuclear dimers irreversibly deposited on square lattices.

    PubMed

    Gimenez, M C; Ramirez-Pastor, A J

    2016-09-01

    The percolation problem of irreversibly deposited heteronuclear dimers on square lattices is studied. A dimer is composed of two segments, and it occupies two adjacent adsorption sites. Each segment can be either a conductive segment (segment type A) or a nonconductive segment (segment type B). Three types of dimers are considered: AA, BB, and AB. The connectivity analysis is carried out by accounting only for the conductive segments (segments type A). The model offers a simplified representation of the problem of percolation of defective (nonideal) particles, where the presence of defects in the system is simulated by introducing a mixture of conductive and nonconductive segments. Different cases were investigated, according to the sequence of deposition of the particles, the types of dimers involved in the process, and the degree of alignment of the deposited objects. By means of numerical simulations and finite-size scaling analysis, the complete phase diagram separating a percolating from a nonpercolating region was determined for each case. Finally, the consistency of our results was examined by comparing with previous data in the literature for linear k-mers (particles occupying k adjacent sites) with defects.

  2. Inactivation of Mycobacterium avium with monochloramine.

    PubMed

    Luh, Jeanne; Tong, Ning; Raskin, Lutgarde; Mariñas, Benito J

    2008-11-01

    Batch experiments were performed to study the inactivation kinetics of Mycobacterium avium in the presence of monochloramine at 5-30 degrees C, pH 6-10, and 0.30-42.3 mg Cl2/ L. For each temperature and pH investigated, limiting high and low inactivation rates were observed for high and low disinfectant concentrations, respectively, within the range investigated. The rate of inactivation transitioned from high to low over a relatively narrow range of intermediate monochloramine concentrations. The observed temperature dependence of inactivation was consistent with an Arrhenius expression with activation energies of 58.0 and 71.7 kJ/mol for the high and low concentration ranges, respectively. The rate of inactivation increased with decreasing pH, consistent with trends reported for the reaction of monochloramine with protein thiols. Experiments performed at pH approximately 3.5 showed that dichloramine was a weaker disinfectant than monochloramine, and that its contribution to the overall inactivation of M. avium with combined chlorine was negligible at pH 6-10. A kinetic model incorporating disinfectant concentration, temperature, and pH effects was used to illustrate that monochloramine efficiency to inactivate M. avium in water could vary broadly from adequate (e.g., 99.9% inactivation efficiency in 32 min at 5 mg Cl2/L, pH 6, 30 degrees C) to impractical (e.g., 99.9% inactivation efficiency in 9 d at 1 mg Cl2/L, pH 9, 5 degrees C).

  3. Optimization of a solar-driven irreversible Carnot heat engine at maximum power output

    SciTech Connect

    Goektun, S.

    1997-08-01

    By employing the energetic optimization technique, the optimum performance of an irreversible Carnot heat engine system driven by a corrugated sheet collector is investigated at maximum power output. The maximum overall efficiency of the system is expressed in terms of the operating parameter of the collector and the cycle-irreversibility parameter of the heat engine.

  4. "Adult" Conceptualization of Irreversibility: Implications for the Development of the Concept of Death.

    ERIC Educational Resources Information Center

    Brent, Sandor B.; Speece, Mark W.

    1993-01-01

    Studies of development of children's understanding of death compares children's understanding against presumed adult concept. Examined validity of adult concept of irreversibility by comparing actual adult data to presumed adult standard and to actual child data. Undergraduates (n=165) completed questionnaire on irreversibility of death. Subjects…

  5. The Impact of Uncertainty and Irreversibility on Investments in Online Learning

    ERIC Educational Resources Information Center

    Oslington, Paul

    2004-01-01

    Uncertainty and irreversibility are central to online learning projects, but have been neglected in the existing educational cost-benefit analysis literature. This paper builds some simple illustrative models of the impact of irreversibility and uncertainty, and shows how different types of cost and demand uncertainty can have substantial impacts…

  6. Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments

    NASA Astrophysics Data System (ADS)

    Becker, Daniel; Kaczmarska, Zuzanna; Arkona, Christoph; Schulz, Robert; Tauber, Carolin; Wolber, Gerhard; Hilgenfeld, Rolf; Coll, Miquel; Rademann, Jörg

    2016-09-01

    Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme-inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.

  7. Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments

    PubMed Central

    Becker, Daniel; Kaczmarska, Zuzanna; Arkona, Christoph; Schulz, Robert; Tauber, Carolin; Wolber, Gerhard; Hilgenfeld, Rolf; Coll, Miquel; Rademann, Jörg

    2016-01-01

    Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme–inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases. PMID:27677239

  8. Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments.

    PubMed

    Becker, Daniel; Kaczmarska, Zuzanna; Arkona, Christoph; Schulz, Robert; Tauber, Carolin; Wolber, Gerhard; Hilgenfeld, Rolf; Coll, Miquel; Rademann, Jörg

    2016-09-28

    Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme-inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.

  9. GnRH Neuron-Specific Ablation of Gαq/11 Results in Only Partial Inactivation of the Neuroendocrine-Reproductive Axis in Both Male and Female Mice: In Vivo Evidence for Kiss1r-Coupled Gαq/11-Independent GnRH Secretion

    PubMed Central

    Navarro, Víctor M.; Ahow, Maryse; Pampillo, Macarena; Nash, Connor; Fayazi, Mehri; Calder, Michele; Elbert, Adrienne; Urbanski, Henryk F.; Wettschureck, Nina; Offermanns, Stefan; Carroll, Rona S.; Bhattacharya, Moshmi; Tobet, Stuart A.; Kaiser, Ursula B.

    2015-01-01

    The gonadotropin-releasing hormone (GnRH) is the master regulator of fertility and kisspeptin (KP) is a potent trigger of GnRH secretion from GnRH neurons. KP signals via KISS1R, a Gαq/11-coupled receptor, and mice bearing a global deletion of Kiss1r (Kiss1r−/−) or a GnRH neuron-specific deletion of Kiss1r (Kiss1rd/d) display hypogonadotropic hypogonadism and infertility. KISS1R also signals via β-arrestin, and in mice lacking β-arrestin-1 or -2, KP-triggered GnRH secretion is significantly diminished. Based on these findings, we hypothesized that ablation of Gαq/11 in GnRH neurons would diminish but not completely block KP-triggered GnRH secretion and that Gαq/11-independent GnRH secretion would be sufficient to maintain fertility. To test this, Gnaq (encodes Gαq) was selectively inactivated in the GnRH neurons of global Gna11 (encodes Gα11)-null mice by crossing Gnrh-Cre and Gnaqfl/fl;Gna11−/− mice. Experimental Gnaqfl/fl;Gna11−/−;Gnrh-Cre (Gnaqd/d) and control Gnaqfl/fl;Gna11−/− (Gnaqfl/fl) littermate mice were generated and subjected to reproductive profiling. This process revealed that testicular development and spermatogenesis, preputial separation, and anogenital distance in males and day of vaginal opening and of first estrus in females were significantly less affected in Gnaqd/d mice than in previously characterized Kiss1r−/− or Kiss1rd/d mice. Additionally, Gnaqd/d males were subfertile, and although Gnaqd/d females did not ovulate spontaneously, they responded efficiently to a single dose of gonadotropins. Finally, KP stimulation triggered a significant increase in gonadotropins and testosterone levels in Gnaqd/d mice. We therefore conclude that the milder reproductive phenotypes and maintained responsiveness to KP and gonadotropins reflect Gαq/11-independent GnRH secretion and activation of the neuroendocrine-reproductive axis in Gnaqd/d mice. SIGNIFICANCE STATEMENT The gonadotropin-releasing hormone (GnRH) is the master

  10. Macroscopic irreversibility and microscopic paradox: A Constructal law analysis of atoms as open systems

    PubMed Central

    Lucia, Umberto

    2016-01-01

    The relation between macroscopic irreversibility and microscopic reversibility is a present unsolved problem. Constructal law is introduced to develop analytically the Einstein’s, Schrödinger’s, and Gibbs’ considerations on the interaction between particles and thermal radiation (photons). The result leads to consider the atoms and molecules as open systems in continuous interaction with flows of photons from their surroundings. The consequent result is that, in any atomic transition, the energy related to the microscopic irreversibility is negligible, while when a great number of atoms (of the order of Avogadro’s number) is considered, this energy related to irreversibility becomes so large that its order of magnitude must be taken into account. Consequently, macroscopic irreversibility results related to microscopic irreversibility by flows of photons and amount of atoms involved in the processes. PMID:27762333

  11. Macroscopic irreversibility and microscopic paradox: A Constructal law analysis of atoms as open systems

    NASA Astrophysics Data System (ADS)

    Lucia, Umberto

    2016-10-01

    The relation between macroscopic irreversibility and microscopic reversibility is a present unsolved problem. Constructal law is introduced to develop analytically the Einstein’s, Schrödinger’s, and Gibbs’ considerations on the interaction between particles and thermal radiation (photons). The result leads to consider the atoms and molecules as open systems in continuous interaction with flows of photons from their surroundings. The consequent result is that, in any atomic transition, the energy related to the microscopic irreversibility is negligible, while when a great number of atoms (of the order of Avogadro’s number) is considered, this energy related to irreversibility becomes so large that its order of magnitude must be taken into account. Consequently, macroscopic irreversibility results related to microscopic irreversibility by flows of photons and amount of atoms involved in the processes.

  12. Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate.

    PubMed

    Covarrubias, M; Wei, A; Salkoff, L; Vyas, T B

    1994-12-01

    The effect of protein kinase C (PKC) on rapid N-type inactivation of K+ channels has not been reported previously. We found that PKC specifically eliminates rapid inactivation of a cloned human A-type K+ channel (hKv3.4), converting this channel from a rapidly inactivating A type to a noninactivating delayed rectifier type. Biochemical analysis showed that the N-terminal domain of hKv3.4 is phosphorylated in vitro by PKC, and mutagenesis experiments revealed that two serines within the inactivation gate at the N-terminus are sites of direct PKC action. Moreover, mutating one of these serines to aspartic acid mimics the action of PKC. Serine phosphorylation may thus prevent rapid inactivation by shielding basic residues known to be critical to the function of the inactivation gate. The regulatory mechanism reported here may have substantial effects on signal coding in the nervous system.

  13. Ribosome Inactivating Proteins from Rosaceae.

    PubMed

    Shang, Chenjing; Rougé, Pierre; Van Damme, Els J M

    2016-08-22

    Ribosome-inactivating proteins (RIPs) are widespread among higher plants of different taxonomic orders. In this study, we report on the RIP sequences found in the genome/transcriptome of several important Rosaceae species, including many economically important edible fruits such as apple, pear, peach, apricot, and strawberry. All RIP domains from Rosaceae share high sequence similarity with conserved residues in the catalytic site and the carbohydrate binding sites. The genomes of Malus domestica and Pyrus communis contain both type 1 and type 2 RIP sequences, whereas for Prunus mume, Prunus persica, Pyrus bretschneideri, and Pyrus communis a complex set of type 1 RIP sequences was retrieved. Heterologous expression and purification of the type 1 as well as the type 2 RIP from apple allowed to characterize the biological activity of the proteins. Both RIPs from Malus domestica can inhibit protein synthesis. Furthermore, molecular modelling suggests that RIPs from Rosaceae possess three-dimensional structures that are highly similar to the model proteins and can bind to RIP substrates. Screening of the recombinant type 2 RIP from apple on a glycan array revealed that this type 2 RIP interacts with terminal sialic acid residues. Our data suggest that the RIPs from Rosaceae are biologically active proteins.

  14. Identifying and Inactivating Bacterial Spores

    NASA Technical Reports Server (NTRS)

    Newcombe, David; Dekas, Anne; Venkateswaran, Kasthuri

    2009-01-01

    Problems associated with, and new strategies for, inactivating resistant organisms like Bacillus canaveralius (found at Kennedy Space Center during a survey of three NASA cleanrooms) have been defined. Identifying the particular component of the spore that allows its heightened resistance can guide the development of sterilization procedures that are targeted to the specific molecules responsible for resistance, while avoiding using unduly harsh methods that jeopardize equipment. The key element of spore resistance is a multilayered protein shell that encases the spore called the spore coat. The coat of the best-studied spore-forming microbe, B. subtilis, consists of at least 45 proteins, most of which are poorly characterized. Several protective roles for the coat are well characterized including resistance to desiccation, large toxic molecules, ortho-phthalaldehyde, and ultraviolet (UV) radiation. One important long-term specific goal is an improved sterilization procedure that will enable NASA to meet planetary protection requirements without a terminal heat sterilization step. This would support the implementation of planetary protection policies for life-detection missions. Typically, hospitals and government agencies use biological indicators to ensure the quality control of sterilization processes. The spores of B. canaveralius that are more resistant to osmotic stress would serve as a better biological indicator for potential survival than those in use currently.

  15. Population Dynamics of Viral Inactivation

    NASA Astrophysics Data System (ADS)

    Freeman, Krista; Li, Dong; Behrens, Manja; Streletzky, Kiril; Olsson, Ulf; Evilevitch, Alex

    We have investigated the population dynamics of viral inactivation in vitrousing time-resolved cryo electron microscopy combined with light and X-ray scattering techniques. Using bacteriophage λ as a model system for pressurized double-stranded DNA viruses, we found that virions incubated with their cell receptor eject their genome in a stochastic triggering process. The triggering of DNA ejection occurs in a non synchronized manner after the receptor addition, resulting in an exponential decay of the number of genome-filled viruses with time. We have explored the characteristic time constant of this triggering process at different temperatures, salt conditions, and packaged genome lengths. Furthermore, using the temperature dependence we determined an activation energy for DNA ejections. The dependences of the time constant and activation energy on internal DNA pressure, affected by salt conditions and encapsidated genome length, suggest that the triggering process is directly dependent on the conformational state of the encapsidated DNA. The results of this work provide insight into how the in vivo kinetics of the spread of viral infection are influenced by intra- and extra cellular environmental conditions. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1252522.

  16. Efficacy of irreversible electroporation in human pancreatic adenocarcinoma: advanced murine model

    PubMed Central

    Philips, Prejesh; Li, Yan; Li, Suping; St Hill, Charles R; Martin, Robert CG

    2015-01-01

    Irreversible electroporation (IRE) is a promising cell membrane ablative modality for pancreatic cancer. There have been recent concerns regarding local recurrence and the potential use of IRE as a debulking (partial ablation) modality. We hypothesize that incomplete ablation leads to early recurrence and a more aggressive biology. We created the first ever heterotopic murine model by inoculating BALB/c nude mice in the hindlimb with a subcutaneous injection of Panc-1 cells, an immortalized human pancreatic adenocarcinoma cell line. Tumors were allowed to grow from 0.75 to 1.5 cm and then treated with the goal of complete ablation or partial ablation using standard IRE settings. Animals were recovered and survived for 2 days (n = 6), 7 (n = 6), 14 (n = 6), 21 (n = 6), 30 (n = 8), and 60 (n = 8) days. All 40 animals/tumors underwent successful IRE under general anesthesia with muscle paralysis. The mean tumor volume of the animals undergoing ablation was 1,447.6 mm3 ± 884). Histologically, in the 14-, 21-, 30-, and 60-day survival groups the entire tumor was nonviable, with a persistent tumor nodule completely replaced fibrosis. In the group treated with partial ablation, incomplete electroporation/recurrences (N = 10 animals) were seen, of which 66% had confluent tumors and this was a significant predictor of recurrence (P < 0.001). Recurrent tumors were also significantly larger (mean 4,578 mm3 ± SD 877 versus completed electroporated tumors 925.8 ± 277, P < 0.001). Recurrent tumors had a steeper growth curve (slope = 0.73) compared with primary tumors (0.60, P = 0.02). Recurrent tumors also had a significantly higher percentage of EpCAM expression, suggestive of stem cell activation. Tumors that recur after incomplete electroporation demonstrate a biologically aggressive tumor that could be more resistant to standard of care chemotherapy. Clinical correlation of this data is limited, but should be considered when IRE of pancreatic cancer is being

  17. Inactivation of nitric oxide by cytochrome c oxidase under steady-state oxygen conditions.

    PubMed

    Unitt, David C; Hollis, Veronica S; Palacios-Callender, Miriam; Frakich, Nanci; Moncada, Salvador

    2010-03-01

    We have developed a respiration chamber that allows intact cells to be studied under controlled oxygen (O(2)) conditions. The system measures the concentrations of O(2) and nitric oxide (NO) in the cell suspension, while the redox state of cytochrome c oxidase is continuously monitored optically. Using human embryonic kidney cells transfected with a tetracycline-inducible NO synthase we show that the inactivation of NO by cytochrome c oxidase is dependent on both O(2) concentration and electron turnover of the enzyme. At a high O(2) concentration (70 microM), and while the enzyme is in turnover, NO generated by the NO synthase upon addition of a given concentration of l-arginine is partially inactivated by cytochrome c oxidase and does not affect the redox state of the enzyme or consumption of O(2). At low O(2) (15 microM), when the cytochrome c oxidase is more reduced, inactivation of NO is decreased. In addition, the NO that is not inactivated inhibits the cytochrome c oxidase, further reducing the enzyme and lowering O(2) consumption. At both high and low O(2) concentrations the inactivation of NO is decreased when sodium azide is used to inhibit cytochrome c oxidase and decrease electron turnover.

  18. Photosensitizers mediated photodynamic inactivation against virus particles.

    PubMed

    Sobotta, Lukasz; Skupin-Mrugalska, Paulina; Mielcarek, Jadwiga; Goslinski, Tomasz; Balzarini, Jan

    2015-01-01

    Viruses cause many diseases in humans from the rather innocent common cold to more serious or chronic, life-threatening infections. The long-term side effects, sometimes low effectiveness of standard pharmacotherapy and the emergence of drug resistance require a search for new alternative or complementary antiviral therapeutic approaches. One new approach to inactivate microorganisms is photodynamic antimicrobial chemotherapy (PACT). PACT has evolved as a potential method to inactivate viruses. The great challenge for PACT is to develop a methodology enabling the effective inactivation of viruses while leaving the host cells as untouched as possible. This review aims to provide some main directions of antiviral PACT, taking into account different photosensitizers, which have been widely investigated as potential antiviral agents. In addition, several aspects concerning PACT as a tool to assure viral inactivation in human blood products will be addressed.

  19. Bacillus Spore Inactivation Methods Affect Detection Assays

    PubMed Central

    Dang, Jessica L.; Heroux, Karen; Kearney, John; Arasteh, Ameneh; Gostomski, Mark; Emanuel, Peter A.

    2001-01-01

    Detection of biological weapons is a primary concern in force protection, treaty verification, and safeguarding civilian populations against domestic terrorism. One great concern is the detection of Bacillus anthracis, the causative agent of anthrax. Assays for detection in the laboratory often employ inactivated preparations of spores or nonpathogenic simulants. This study uses several common biodetection platforms to detect B. anthracis spores that have been inactivated by two methods and compares those data to detection of spores that have not been inactivated. The data demonstrate that inactivation methods can affect the sensitivity of nucleic acid- and antibody-based assays for the detection of B. anthracis spores. These effects should be taken into consideration when comparing laboratory results to data collected and assayed during field deployment. PMID:11472945

  20. Irreversible electroporation: Just another form of thermal therapy?

    PubMed Central

    van Gemert, Martin J C; Wagstaff, Peter G K; de Bruin, Daniel M; van Leeuwen, Ton G; van der Wal, Allard C; Heger, Michal; van der Geld, Cees W M

    2015-01-01

    Background Irreversible electroporation (IRE) is (virtually) always called non-thermal despite many reports showing that significant Joule heating occurs. Our first aim is to validate with mathematical simulations that IRE as currently practiced has a non-negligible thermal response. Our second aim is to present a method that allows simple temperature estimation to aid IRE treatment planning. Methods We derived an approximate analytical solution of the bio-heat equation for multiple 2-needle IRE pulses in an electrically conducting medium, with and without a blood vessel, and incorporated published observations that an electric pulse increases the medium's electric conductance. Results IRE simulation in prostate-resembling tissue shows thermal lesions with 67–92°C temperatures, which match the positions of the coagulative necrotic lesions seen in an experimental study. Simulation of IRE around a blood vessel when blood flow removes the heated blood between pulses confirms clinical observations that the perivascular tissue is thermally injured without affecting vascular patency. Conclusions The demonstration that significant Joule heating surrounds current multiple-pulsed IRE practice may contribute to future in-depth discussions on this thermal issue. This is an important subject because it has long been under-exposed in literature. Its awareness pleads for preventing IRE from calling “non-thermal” in future publications, in order to provide IRE-users with the most accurate information possible. The prospect of thermal treatment planning as outlined in this paper likely aids to the important further successful dissemination of IRE in interventional medicine. Prostate 75:332–335, 2015. © 2014 The Authors. The Prostate Published by Wiley Periodicals, Inc. PMID:25327875

  1. Irreversible Collective Migration of Cyanobacteria in Eutrophic Conditions

    PubMed Central

    Dervaux, Julien; Mejean, Annick; Brunet, Philippe

    2015-01-01

    In response to natural or anthropocentric pollutions coupled to global climate changes, microorganisms from aquatic environments can suddenly accumulate on water surface. These dense suspensions, known as blooms, are harmful to ecosystems and signicantly degrade the quality of water resources. In order to determine the physico-chemical parameters involved in their formation and quantitatively predict their appearance, we successfully reproduced irreversible cyanobacterial blooms in vitro. By combining chemical, biochemical and hydrodynamic evidences, we identify a mechanism, unrelated to the presence of internal gas vesicles, allowing the sudden collective upward migration in test tubes of several cyanobacterial strains (Microcystis aeruginosa PCC 7005, Microcystis aeruginosa PCC 7806 and Synechocystis sp. PCC 6803). The final state consists in a foamy layer of biomass at the air-liquid interface, in which micro-organisms remain alive for weeks, the medium lying below being almost completely depleted of cyanobacteria. These "laboratory blooms" start with the aggregation of cells at high ionic force in cyanobacterial strains that produce anionic extracellular polymeric substances (EPS). Under appropriate conditions of nutrients and light intensity, the high photosynthetic activity within cell clusters leads the dissolved oxygen (DO) to supersaturate and to nucleate into bubbles. Trapped within the EPS, these bubbles grow until their buoyancy pulls the biomass towards the free surface. By investigating a wide range of spatially homogeneous environmental conditions (illumination, salinity, cell and nutrient concentration) we identify species-dependent thresholds and timescales for bloom formation. We conclude on the relevance of such results for cyanobacterial bloom formation in the environment and we propose an ecient method for biomass harvesting in bioreactors. PMID:25799424

  2. Reversible and irreversible processing of biogenic olefins on acidic aerosols

    NASA Astrophysics Data System (ADS)

    Liggio, J.; Li, S.-M.

    2008-04-01

    Recent evidence has suggested that heterogeneous chemistry of oxygenated hydrocarbons, primarily carbonyls, plays a role in the formation of secondary organic aerosol (SOA); however, evidence is emerging that direct uptake of alkenes on acidic aerosols does occur and can contribute to SOA formation. In the present study, significant uptake of monoterpenes, oxygenated monoterpenes and sesquiterpenes to acidic sulfate aerosols is found under various conditions in a reaction chamber. Proton transfer mass spectrometry is used to quantify the organic gases, while an aerosol mass spectrometer is used to quantify the organic mass uptake and obtain structural information for heterogeneous products. Aerosol mass spectra are consistent with several mechanisms including acid catalyzed olefin hydration, cationic polymerization and organic ether formation, while measurable decreases in the sulfate mass on a per particle basis suggest that the formation of organosulfate compounds is also likely. A portion of the heterogeneous reactions appears to be reversible, consistent with reversible olefin hydration reactions. A slow increase in the organic mass after a fast initial uptake is attributed to irreversible reactions, consistent with polymerization and organosulfate formation. Uptake coefficients (γ) were estimated for a fast initial uptake governed by the mass accommodation coefficient (α) and ranged from 1×10-6-2.5×10-2. Uptake coefficients for a subsequent slower reactive uptake ranged from 1×10-7-1×10-4. These processes may potentially lead to a considerable amount of SOA from the various biogenic hydrocarbons under acidic conditions, which can be highly significant for freshly nucleated aerosols, particularly given the large array of atmospheric olefins.

  3. Reversible and irreversible processing of biogenic olefins on acidic aerosols

    NASA Astrophysics Data System (ADS)

    Liggio, J.; Li, S.-M.

    2007-08-01

    Recent evidence has suggested that heterogeneous chemistry of oxygenated hydrocarbons, primarily carbonyls, plays a role in the formation of secondary organic aerosol (SOA); however, evidence is emerging that direct uptake of alkenes on acidic aerosols does occur and can contribute to SOA formation. In the present study, significant uptake of monoterpenes, oxygenated monoterpenes and sesquiterpenes to acidic sulfate aerosols is found under various conditions in a reaction chamber. Proton transfer mass spectrometry is used to quantify the organic gases, while an aerosol mass spectrometer is used to quantify the organic mass uptake and obtain structural information for heterogeneous products. Aerosol mass spectra are consistent with several mechanisms including acid catalyzed olefin hydration, cationic polymerization and organic ester formation, while measurable decreases in the sulfate mass on a per particle basis suggest that the formation of organosulfate compounds is also likely. A portion of the heterogeneous reactions appears to be reversible, consistent with reversible olefin hydration reactions. A slow increase in the organic mass after a fast initial uptake is attributed to irreversible reactions, consistent with polymerization and organosulfate formation. Uptake coefficients (γ) were estimated for a fast initial uptake governed by the mass accommodation coefficient (α) and ranged from 1×10-6-2.5×10-2. Uptake coefficients for a subsequent slower reactive uptake ranged from 1×10-7-1×10-4. These processes are estimated to potentially produce greater than 2.5 μg m-3 of SOA from the various biogenic hydrocarbons under atmospheric conditions, which can be highly significant given the large array of atmospheric olefins.

  4. Microbial Inactivation by Ultrasound Assisted Supercritical Fluids

    NASA Astrophysics Data System (ADS)

    Benedito, Jose; Ortuño, Carmen; Castillo-Zamudio, Rosa Isela; Mulet, Antonio

    A method combining supercritical carbon dioxide (SC-CO2) and high power ultrasound (HPU) has been developed and tested for microbial/enzyme inactivation purposes, at different process conditions for both liquid and solid matrices. In culture media, using only SC-CO2, the inactivation rate of E. coli and S. cerevisiae increased with pressure and temperature; and the total inactivation (7-8 log-cycles) was attained after 25 and 140 min of SC-CO2 (350 bar, 36 °C) treatment, respectively. Using SC-CO2+HPU, the time for the total inactivation of both microorganisms was reduced to only 1-2 min, at any condition selected. The SC-CO2+HPU inactivation of both microorganisms was slower in juices (avg. 4.9 min) than in culture media (avg. 1.5 min). In solid samples (chicken, turkey ham and dry-cured pork cured ham) treated with SC-CO2 and SC-CO2+HPU, the inactivation rate of E. coli increased with temperature. The application of HPU to the SC-CO2 treatments accelerated the inactivation rate of E. coli and that effect was more pronounced in treatments with isotonic solution surrounding the solid food samples. The application of HPU enhanced the SC-CO2 inactivation mechanisms of microorganisms, generating a vigorous agitation that facilitated the CO2 solubilization and the mass transfer process. The cavitation generated by HPU could damage the cell walls accelerating the extraction of vital constituents and the microbial death. Thus, using the combined technique, reasonable industrial processing times and mild process conditions could be used which could result into a cost reduction and lead to the minimization in the food nutritional and organoleptic changes.

  5. Inactivation of Viruses by Benzalkonium Chloride

    PubMed Central

    Armstrong, J. A.; Froelich, E. J.

    1964-01-01

    Benzalkonium chloride (as Roccal or Zephiran) was found to inactivate influenza, measles, canine distemper, rabies, fowl laryngotracheitis, vaccinia, Semliki Forest, feline pneumonitis, meningopneumonitis, and herpes simplex viruses after 10 min of exposure at 30 C or at room temperature. Poliovirus and encephalomyocarditis virus were not inactivated under the same conditions. It was concluded that all viruses tested were sensitive except members of the picorna group. The literature was reviewed. PMID:4288740

  6. Modeling Thermal Inactivation of Bacillus Spores

    DTIC Science & Technology

    2009-03-01

    models which theorize damage to Bacillus spores by various methods. These models use multiple Bacillus species such as anthracis, cereus , and subtilis...MODELING THERMAL INACTIVATION OF BACILLUS SPORES THESIS Emily A. Knight Captain, USAF AFIT/GAM/ENC/09-01 DEPARTMENT OF THE AIR FORCE AIR UNIVERSITY...United States Government. AFIT/GAM/ENC/09-01 MODELING THERMAL INACTIVATION OF BACILLUS SPORES THESIS Presented to the Faculty Department of Mathematics

  7. Azide protection of bacteroides superoxide dismutases from inactivation by hydrogen peroxide

    SciTech Connect

    Barkley, K.B.; Gregory, E.M.

    1986-05-01

    The anaerobes Bacteroides fragilis, B. distasonis and B. thetaiotaomicron produce an iron-containing superoxide dismutase (FeSOD). These FeSODs are reversibly inhibited by 1 mM azide (NaN/sub 3/) and are irreversibly inactivated upon incubation with hydrogen peroxide (H/sub 2/O/sub 2/). H/sub 2/O/sub 2/ inactivation of the enzyme likely depends on a Fenton type reaction with the production of hydroxyl radical (OH). Addition of NaN/sub 3/ to the enzyme solution decreased the rate of inactivation by H/sub 2/O/sub 2/. After 20 minutes incubation of purified B. distasonis FeSOD with 2.5 mM H/sub 2/O/sub 2/, 61% of the initial enzymatic activity remained when 1 mM NaN/sub 3/ was also present compared with 29% activity without NaN/sub 3/. Similar results were seen with FeSOD from B. fragilis and B. thetaiotaomicron. Metal analyses of the native, peroxidized, and NaN/sub 3/ protected samples are consistent with loss of Fe from the enzyme upon peroxidation, but retention of Fe and enzymatic activity in the NaN/sub 3/ protected sample. Protection of FeSOD activity from H/sub 2/O/sub 2/ inactivation was dependent on NaN/sub 3/ concentration. Anionic hydroxyl radical scavengers, such as urate and xanthine did not significantly protect the enzyme. The results are consistent with binding of azide to the active site either preventing entry of H/sub 2/O/sub 2/ or altering Fe redox potential, preventing OH production.

  8. Ozone-induced inactivation of antioxidant enzymes.

    PubMed

    Lee, Yong-Ki; Mok Kim, Sang; Han, Sanghwa

    2003-10-01

    Ozone is an air pollutant that damages a variety of biomolecules. We investigated ozone-induced inactivation of three major antioxidant enzymes. Cu/Zn superoxide dismutase was inactivated by ozone in a concentration-dependent manner. The concentration of ozone for 50% inactivation was approximately 45 microM when 10 microM Cu/Zn superoxide dismutase was incubated for 30 min in the presence of ozone. SDS-polyacrylamide gel electrophoresis (PAGE) showed that the enzyme was randomly fragmented. Both ascorbate and glutathione were very effective in protecting Cu/Zn superoxide dismutase from ozone-induced inactivation. The other two enzymes, catalase and glutathione peroxidase, were much more resistant to ozone than Cu/Zn superoxide dismutase. The ozone concentrations for 50% inactivation of 10 microM catalase and glutathione peroxidase were 500 and 240 microM, respectively. SDS-PAGE demonstrated that ozone caused formation of high molecular weight aggregates in catalase and dimerization in glutathione peroxidase. Glutathione protected catalase and glutathione peroxidase from ozone but the effective concentrations were much higher than that for Cu/Zn superoxide dismutase. Ascorbate was almost ineffective. The result suggests that, among the three antioxidant enzymes, Cu/Zn superoxide dismutase is a major target for ozone-induced inactivation and both glutathione and ascorbate are very effective in protecting the enzyme from ozone.

  9. Photodynamic-induced inactivation of Propionibacterium acnes

    NASA Astrophysics Data System (ADS)

    Koenig, Karsten; Teschke, M.; Eick, Stephen G.; Pfister, W.; Meyer, Herbert; Halbhuber, Karl-Juergen

    1998-05-01

    We report on photodynamically induced inactivation of the skin bacterium Propionibacterium acnes (P. acnes) using endogenous as well as exogenous photosensitizers and red light sources. P. acnes is involved in the pathogenesis of the skin disease acne vulgaris. The skin bacterium is able to synthesize the metal-free fluorescent porphyrins protoporphyrin IX (PP) and coproporphyrin (CP) as shown by in situ spectrally-resolved detection of natural autofluorescence of human skin and bacteria colonies. These naturally occurring intracellular porphyrins act as efficient endogenous photosensitizers. Inactivation of P. acnes suspensions was achieved by irradiation with He-Ne laser light in the red spectral region (632.8 nm). We monitored the photodynamically-induced death of single bacteria using a fluorescent viability kit in combination with confocal laser scanning microscopy. In addition, the photo-induced inactivation was calculated by CFU (colony forming units) determination. We found 633 nm-induced inactivation (60 mW, 0.12 cm2 exposure area, 1 hour irradiation) of 72% in the case of non-incubated bacteria based on the destructive effect of singlet oxygen produced by red light excited endogenous porphyrins and subsequent energy transfer to molecular oxygen. In order to achieve a nearly complete inactivation within one exposure procedure, the exogenous photosensitizer Methylene Blue (Mb) was added. Far red exposure of Mb-labeled bacteria using a krypton ion laser at 647 nm and 676 nm resulted in 99% inactivation.

  10. Physicochemical stability and inactivation of human and simian rotaviruses

    SciTech Connect

    Meng, Z.D.; Birch, C.; Heath, R.; Gust, I.

    1987-04-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H/sub 2/O/sub 2/ for 1 h each.

  11. Virus inactivation studies using ion beams, electron and gamma irradiation

    NASA Astrophysics Data System (ADS)

    Smolko, Eduardo E.; Lombardo, Jorge H.

    2005-07-01

    Known methods of virus inactivation are based on the chemical action of some substances such as acetylethylenimine, betapropiolactone, glycidalaldehyde, formaldehyde, etc. In such a process, the viral suspension should be kept at room or higher temperatures for 24-48 h. Under these conditions, physical and chemical agents act to degrade the virus antigenic proteins. On the contrary with ionizing radiations at low temperatures, the treatment does not cause such degradation allowing the study of different viral functions. In this work, particle (α, d and ß) and γ irradiations were used for partial and total inactivation of Foot and Mouth Disease Virus (FMDV), Rauscher Leukemia Virus (RLV) and Herpes Simplex Virus (HSV). Obtention of the D37 dose from survival curves and the application of the target theory, permitted the determination of molecular weight of the nucleic acid genomes, EBR values and useful information for vaccine preparation. For RLV virus, a two target model of the RNA genome was deduced in accordance with biological information while from data from the literature and our own work on the structure of the scrapie prion, considering the molecular weight obtained by application of the theory, a new model for prion replication is presented, based on a trimer molecule.

  12. Vaccine-associated enhanced respiratory disease is influenced by hemagglutinin and neuraminidase in whole inactivated influenza virus vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple subtypes and many antigenic variants of influenza A virus (IAV) co-circulate in swine in the USA, complicating effective use of commercial vaccines to control disease and transmission. Whole inactivated virus (WIV) vaccines may provide partial protection against IAV with substantial antigen...

  13. [Amphotericin B channel conductance inactivation].

    PubMed

    Ibragimova, V Kh; Alieva, I N; Aliev, D I

    2003-01-01

    Effects induced in bilayer lipid membranes by amphotericin B and its alkyl derivatives was analysed. Inactivation of the antibiotic-dependent multichannel membrane conductance was discovered. Kinetics of membrane conductivity was shown to depend on the antibiotic concentration in the membrane. At concentrations between 10(-8) and 10(-7) M, the resulting conductance appeared to the transient. We suggest that the phenomenon of biphasic kinetics of membrane conductance is the result of a consecutive transformation of polyene channels in the membrane: half-pores are assembled on either side of membrane-nonconducting 1; two half-pores combine to build up a conducting channels-conducting 2, and the conducting channels are disassemled to monomers and nonconducting self-associated forms inside the membrane-disassembled state (nonconducting 3). To explain the transient characteristics of the induced conductance, it is proposed that the antibiotic, present in the solution under self-associated form, binds the membrane and forms pores, then dissociates in the bilayer in a non-active monomeric form. The existence of definite monomers and nonconducting self-associated forms of amphotericin B molecules inside the membrane was estimated from the dependence of kinetic conductance of lipid membranes of amphotericin B and its alkyl derivatives, when the antibiotics are washed out from aqueous medium. Equilibrium between different antibiotic assemblies inside the membrane was demonstrated by the kinetics of conductance decrease following washing the antibiotic. Using circular dichroism measurements, we observed that amphotericin B alkyl derivatives were in self-associated form being susceptible to form pores across cholesterol-containing membranes. The phenomenon of biophasic kinetics was observed only in the cholesterol-containing membrane. The substitution of membrane cholesterol for ergosterol provides monotonic kinetics of membrane conductance at any antibiotic concentration.

  14. Quantifying irreversible movement in steep, fractured bedrock permafrost on Matterhorn (CH)

    NASA Astrophysics Data System (ADS)

    Weber, Samuel; Beutel, Jan; Faillettaz, Jérome; Hasler, Andreas; Krautblatter, Michael; Vieli, Andreas

    2017-02-01

    Understanding rock slope kinematics in steep, fractured bedrock permafrost is a challenging task. Recent laboratory studies have provided enhanced understanding of rock fatigue and fracturing in cold environments but were not successfully confirmed by field studies. This study presents a unique time series of fracture kinematics, rock temperatures and environmental conditions at 3500 m a. s. l. on the steep, strongly fractured Hörnligrat of the Matterhorn (Swiss Alps). Thanks to 8 years of continuous data, the longer-term evolution of fracture kinematics in permafrost can be analyzed with an unprecedented level of detail. Evidence for common trends in spatiotemporal pattern of fracture kinematics could be found: a partly reversible seasonal movement can be observed at all locations, with variable amplitudes. In the wider context of rock slope stability assessment, we propose separating reversible (elastic) components of fracture kinematics, caused by thermoelastic strains, from the irreversible (plastic) component due to other processes. A regression analysis between temperature and fracture displacement shows that all instrumented fractures exhibit reversible displacements that dominate fracture kinematics in winter. Furthermore, removing this reversible component from the observed displacement enables us to quantify the irreversible component. From this, a new metric - termed index of irreversibility - is proposed to quantify relative irreversibility of fracture kinematics. This new index can identify periods when fracture displacements are dominated by irreversible processes. For many sensors, irreversible enhanced fracture displacement is observed in summer and its initiation coincides with the onset of positive rock temperatures. This likely indicates thawing-related processes, such as meltwater percolation into fractures, as a forcing mechanism for irreversible displacements. For a few instrumented fractures, irreversible displacements were found at the

  15. Irreversible Electroporation Near the Heart: Ventricular Arrhythmias Can Be Prevented With ECG Synchronization

    PubMed Central

    Deodhar, Ajita; Dickfeld, Timm; Single, Gordon W.; Hamilton, William C.; Thornton, Raymond H.; Sofocleous, Constantinos T.; Maybody, Majid; Gónen, Mithat; Rubinsky, Boris; Solomon, Stephen B.

    2013-01-01

    OBJECTIVE Irreversible electroporation is a nonthermal ablative tool that uses direct electrical pulses to create irreversible membrane pores and cell death. The ablation zone is surrounded by a zone of reversibly increased permeability; either zone can cause cardiac arrhythmias. Our purpose was to establish a safety profile for the use of irreversible electroporation close to the heart. MATERIALS and METHODS The effect of unsynchronized and synchronized (with the R wave on ECG) irreversible electroporation in swine lung and myocardium was studied in 11 pigs. Twelve lead ECG recordings were analyzed by an electrophysiologist for the presence of arrhythmia. Ventricular arrhythmias were categorized as major events. Minor events included all other dysrhythmias or ECG changes. Cardiac and lung tissue was submitted for histopathologic analysis. Electrical field modeling was performed to predict the distance from the applicators over which cells show electroporation-induced increased permeability. RESULTS At less than or equal to 1.7 cm from the heart, fatal (major) events occurred with all unsynchronized irreversible electroporation. No major and three minor events were seen with synchronized irreversible electroporation. At more than 1.7 cm from the heart, two minor events occurred with only unsynchronized irreversible electroporation. Electrical field modeling correlates well with the clinical results, revealing increased cell membrane permeability up to 1.7 cm away from the applicators. Complete lung ablation without intervening live cells was seen. No myocardial injury was seen. CONCLUSION Unsynchronized irreversible electroporation close to the heart can cause fatal ventricular arrhythmias. Synchronizing irreversible electroporation pulse delivery with absolute refractory period avoids significant cardiac arrhythmias. PMID:21343484

  16. Effect of graphite surface structure on initial irreversible reaction in graphite anodes

    SciTech Connect

    Suzuki, Kimihito; Hamada, Takeshi; Sugiura, Tsutomu

    1999-03-01

    The initial irreversible reaction that occurs in graphite anodes during the first lithium intercalation in lithium rechargeable batteries was studied in view of graphite surface structure. Graphitized mesophase spheres and pitch-based carbon fibers, which show low irreversible capacity, were shown to have turbostatic surface regions and highly graphitized cores using Ar-ion laser Raman spectroscopy. Burning off these surface regions resulted in remarkable increases of initial irreversible capacity. Those results can be explained by a proposed model that a turbostatic structure of the graphite surface region resists drastic swelling of interlayer spaces arising from cointercalation of solvated ions and depresses the side reaction.

  17. Mesoscale modeling of irreversible volume growth in powders of anisotropic crystals

    SciTech Connect

    Gee, R; Maiti, A; Fried, L

    2006-05-05

    Careful thermometric analysis (TMA) on powders of micron-sized triamino-trinitrobenzene (TATB) crystallites are shown to display irreversible growth in volume when subjected to repeated cycles of heating and cooling. Such behavior is counter-intuitive to typical materials response to simulated annealing cycles in atomic-scale molecular dynamics. However, through coarse-grained simulations using a mesoscale Hamiltonian we quantitatively reproduce irreversible growth behavior in such powdered material. We demonstrate that irreversible growth happens only in the presence of intrinsic crystalline anisotropy, and is mediated by particles much smaller than the average crystallite size.

  18. A fingerprint encryption scheme based on irreversible function and secure authentication.

    PubMed

    Yang, Yijun; Yu, Jianping; Zhang, Peng; Wang, Shulan

    2015-01-01

    A fingerprint encryption scheme based on irreversible function has been designed in this paper. Since the fingerprint template includes almost the entire information of users' fingerprints, the personal authentication can be determined only by the fingerprint features. This paper proposes an irreversible transforming function (using the improved SHA1 algorithm) to transform the original minutiae which are extracted from the thinned fingerprint image. Then, Chinese remainder theorem is used to obtain the biokey from the integration of the transformed minutiae and the private key. The result shows that the scheme has better performance on security and efficiency comparing with other irreversible function schemes.

  19. A Fingerprint Encryption Scheme Based on Irreversible Function and Secure Authentication

    PubMed Central

    Yu, Jianping; Zhang, Peng; Wang, Shulan

    2015-01-01

    A fingerprint encryption scheme based on irreversible function has been designed in this paper. Since the fingerprint template includes almost the entire information of users' fingerprints, the personal authentication can be determined only by the fingerprint features. This paper proposes an irreversible transforming function (using the improved SHA1 algorithm) to transform the original minutiae which are extracted from the thinned fingerprint image. Then, Chinese remainder theorem is used to obtain the biokey from the integration of the transformed minutiae and the private key. The result shows that the scheme has better performance on security and efficiency comparing with other irreversible function schemes. PMID:25873989

  20. A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma

    PubMed Central

    Yan, Li; Chen, Yong-Liang; Su, Ming; Liu, Tian; Xu, Kai; Liang, Feng; Gu, Wan-Qing; Lu, Shi-Chun

    2016-01-01

    Background: Locally advanced pancreatic carcinoma (LAPC) is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation (IRE) has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. Methods: Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. Results: All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed (16%): two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. Conclusions: IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy. PMID:27958223

  1. State-dependent inactivation of the Kv3 potassium channel.

    PubMed Central

    Marom, S; Levitan, I B

    1994-01-01

    Inactivation of Kv3 (Kv1.3) delayed rectifier potassium channels was studied in the Xenopus oocyte expression system. These channels inactivate slowly during a long depolarizing pulse. In addition, inactivation accumulates in response to a series of short depolarizing pulses (cumulative inactivation), although no significant inactivation occurs within each short pulse. The extent of cumulative inactivation does not depend on the voltage during the depolarizing pulse, but it does vary in a biphasic manner as a function of the interpulse duration. Furthermore, the rate of cumulative inactivation is influenced by changing the rate of deactivation. These data are consistent with a model in which Kv3 channel inactivation is a state-dependent and voltage-independent process. Macroscopic and single channel experiments indicate that inactivation can occur from a closed (silent) state before channel opening. That is, channels need not open to inactivate. The transition that leads to the inactivated state from the silent state is, in fact, severalfold faster then the observed inactivation of current during long depolarizing pulses. Long pulse-induced inactivation appears to be slow, because its rate is limited by the probability that channels are in the open state, rather than in the silent state from which they can inactivate. External potassium and external calcium ions alter the rates of cumulative and long pulse-induced inactivation, suggesting that antagonistic potassium and calcium binding steps are involved in the normal gating of the channel. PMID:7948675

  2. Succination of proteins by fumarate: mechanism of inactivation of glyceraldehyde-3-phosphate dehydrogenase in diabetes.

    PubMed

    Blatnik, Matthew; Thorpe, Suzanne R; Baynes, John W

    2008-04-01

    S-(2-succinyl)cysteine (2SC) is a chemical modification of proteins formed by a Michael addition reaction between the Krebs cycle intermediate, fumarate, and thiol groups in protein--a process known as succination of protein. Succination causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in vitro. GAPDH was immunoprecipitated from muscle of diabetic rats, then analyzed by ultra-performance liquid chromatography-electrospray ionization-mass spectroscopy. Succination of GAPDH was increased in muscle of diabetic rats, and the extent of succination correlated strongly with the decrease in specific activity of the enzyme. We propose that 2SC is a biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins may provide the chemical link between glucotoxicity and the pathogenesis of diabetic complications.

  3. Inactivation of surfactant in rat lungs.

    PubMed

    Bruni, R; Fan, B R; David-Cu, R; Taeusch, H W; Walther, F J

    1996-02-01

    Although surfactant replacement therapy has dramatically improved the outcome of premature infants with respiratory distress syndrome, approximately 30% of treated infants show a transient or no response. Nonresponse to surfactant replacement therapy may be due to extreme lung immaturity and possibly surfactant inactivation. Surfactant inactivation involves aspecific biophysical events, such as interference with the formation or activity of an alveolar monolayer, and specific interactions with serum proteins, including antibodies, leaking into the alveolar space. As formulations containing surfactant proteins appear to better tolerate serum inactivation, we used an excised rat lung model to compare the susceptibility to serum inactivation of a mixture of synthetic phospholipids selected from surfactant lipid constituents, Exosurf (a protein-free synthetic surfactant), Survanta [containing surfactant proteins B and C (SP-B and -C)], and a porcine surfactant (containing SP-A, -B, and -C). For each of these preparations, we used pressure/volume determinations as an in situ measure of surfactant activity and retested the same preparations after mixing with human serum, a nonspecific surfactant inactivator. Human serum inactivated porcine surfactant to a lesser extent than Survanta, Exosurf, or synthetic phospholipids. Temperature exerted a significant effect on deflation stability, as shown by a greater lung compliance in untreated, normal lungs and a larger improvement in compliance after treating lavaged lungs with synthetic phospholipids at 37 degrees C than at 22 degrees C. We conclude that surfactant containing SP-A, -B, and -C is only moderately susceptible to inactivation with whole serum and may therefore exert a greater clinical response than protein-free surfactants or those containing only SP-B and -C.

  4. Partial (focal) seizure

    MedlinePlus

    ... Jacksonian seizure; Seizure - partial (focal); Temporal lobe seizure; Epilepsy - partial seizures ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

  5. Partial tooth gear bearings

    NASA Technical Reports Server (NTRS)

    Vranish, John M. (Inventor)

    2010-01-01

    A partial gear bearing including an upper half, comprising peak partial teeth, and a lower, or bottom, half, comprising valley partial teeth. The upper half also has an integrated roller section between each of the peak partial teeth with a radius equal to the gear pitch radius of the radially outwardly extending peak partial teeth. Conversely, the lower half has an integrated roller section between each of the valley half teeth with a radius also equal to the gear pitch radius of the peak partial teeth. The valley partial teeth extend radially inwardly from its roller section. The peak and valley partial teeth are exactly out of phase with each other, as are the roller sections of the upper and lower halves. Essentially, the end roller bearing of the typical gear bearing has been integrated into the normal gear tooth pattern.

  6. DL-canaline and 5-fluoromethylornithine. Comparison of two inactivators of ornithine aminotransferase.

    PubMed Central

    Bolkenius, F N; Knödgen, B; Seiler, N

    1990-01-01

    5-Fluoromethylornithine (5FMOrn) is an enzyme-activated irreversible inhibitor or ornithine aminotransferase (L-ornithine:2-oxo-acid 5-aminotransferase, OAT). For purified rat liver OAT, Ki(app.) was found to be 30 microM. and tau 1/2 = 4 min. Of the four stereomers of 5FMOrn only one reacts with OAT. The formation of a chromophore with an absorption maximum at 458 nm after inactivation of OAT by 5FMOrn suggests the formation of an enamine intermediate, which is slowly hydrolysed to release an unsaturated ketone. L-Canaline [(S)-2-amino-4-amino-oxybutyric acid] is a well-known irreversible inhibitor of OAT. Not only the natural L-enantiomer but also the D-enantiomer reacts by oxime formation with pyridoxal 5'-phosphate in the active site of the enzyme, although considerably more slowly. This demonstrates that the stereochemistry at C-2 of ornithine is not absolutely stringent. In vitro, canaline reacted faster than 5FMOrn with OAT. In vivo, however, only incomplete OAT inhibition was observed with canaline. Whereas intraperitoneal administration of 10 mg of 5FMOrn/kg body wt. to mice was sufficient to inactivate OAT in brain and liver by 90% for 24 h, 500 mg of DL-canaline/kg body wt. only produced a transient inhibition of 65-70%. The accumulation of ornithine in these tissues was considerably slower and the maximum concentrations lower than were achieved with 5FMOrn. It appears that DL-canaline, in contrast with 5FMOrn, is not useful as a tool in studies of biological consequences of OAT inhibition. PMID:2363680

  7. Mechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivation.

    PubMed

    Rosemary Bastian, Arangassery; Nangarlia, Aakansha; Bailey, Lauren D; Holmes, Andrew; Kalyana Sundaram, R Venkat; Ang, Charles; Moreira, Diogo R M; Freedman, Kevin; Duffy, Caitlin; Contarino, Mark; Abrams, Cameron; Root, Michael; Chaiken, Irwin

    2015-01-02

    Entry of HIV-1 into host cells remains a compelling yet elusive target for developing agents to prevent infection. A peptide triazole (PT) class of entry inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions of the Env protein at host cell receptor binding sites, inhibit cell infection, and cause envelope spike protein breakdown, including gp120 shedding and, for some variants, virus membrane lysis. We found that gold nanoparticle-conjugated forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought to reveal the mechanism of potency enhancement underlying nanoparticle conjugate function. We found that altering the physical properties of the nanoparticle conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on the AuNP surface, enhanced potency of infection inhibition to impressive picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less susceptible to reduction of antiviral potency when the density of PT-competent Env spikes on the virus was reduced by incorporating a peptide-resistant mutant gp120. We conclude that potency enhancement of virolytic activity and corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation derives from multivalent contact between the nanoconjugates and metastable Env spikes on the HIV-1 virus. The findings reveal that multispike engagement can exploit the metastability built into virus the envelope to irreversibly inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based antiviral agents for HIV-1 specifically and putatively for metastable enveloped viruses generally.

  8. Functional inactivation of lymphocytes by methylene blue with visible light.

    PubMed

    Zhang, Bo; Cheng, Zhenzhen; Mo, Qin; Wang, Li; Wang, Xun; Wu, Xiaofei; Jia, Yao; Huang, Yuwen

    2015-10-01

    Transfusion of allogeneic white blood cells (WBCs) may cause adverse reactions in immunocompromised recipients, including transfusion-associated graft-versus-host disease (TA-GVHD), which is often fatal and incurable. In this study, the in vitro effect of methylene blue with visible light (MB + L) treatment on lymphocyte proliferation and cytokine production was measured to investigate whether MB + L can be used to prevent immune reactions that result from transfused lymphocytes. WBCs and 3 μM of MB were mixed and transferred into medical PVC bags, which were then exposed to visible light. Gamma irradiation was conducted as a parallel positive control. The cells without treatment were used as untreated group. All the groups were tested for the ability of cell proliferation and cytokine production upon stimulation. After incubation with mitogen phytohemagglutinin (PHA) or plate-bound anti-CD3 plus anti-CD28, the proliferation of MB + L/gamma-irradiation treated lymphocytes was significantly inhibited (P < 0.01) as compared to the untreated ones; the proliferation inhibitive rate of the MB + L group was even higher than that of gamma-irradiated cells (73.77% ± 28.75% vs. 44.72% ± 38.20%). MB + L treated cells incubated up to 7 days with PHA also showed no significant proliferation. The levels of TNF-α, IFN-γ, IL-6, IL-8, IL-10 and IL-1β present in the supernatant of MB + L treated lymphocytes upon stimulation were significantly lower than those of untreated lymphocytes. These results demonstrated that MB + L treatment functionally and irreversibly inactivated lymphocytes by inhibiting lymphocyte proliferation and the production of cytokines. MB + L treatment might be a promising method for the prevention of adverse immune responses caused by WBCs.

  9. Inactivation of microbial arginine deiminases by L-canavanine.

    PubMed

    Li, Ling; Li, Zhimin; Chen, Danqi; Lu, Xuefeng; Feng, Xiaohua; Wright, Elizabeth C; Solberg, Nathan O; Dunaway-Mariano, Debra; Mariano, Patrick S; Galkin, Andrey; Kulakova, Liudmila; Herzberg, Osnat; Green-Church, Kari B; Zhang, Liwen

    2008-02-13

    Arginine deiminase (ADI) catalyzes the hydrolytic conversion of L-arginine to ammonia and L-citrulline as part of the energy-producing L-arginine degradation pathway. The chemical mechanism for ADI catalysis involves initial formation and subsequent hydrolysis of a Cys-alkylthiouronium ion intermediate. The structure of the Pseudomonas aeruginosa ADI-(L-arginine) complex guided the design of arginine analogs that might react with the ADIs to form inactive covalent adducts during catalytic turnover. One such candidate is L-canavanine, in which an N-methylene of L-arginine is replaced by an N-O. This substance was shown to be a slow substrate-producing O-ureido-L-homoserine. An in depth kinetic and mass spectrometric analysis of P. aeruginosa ADI inhibition by L-canavanine showed that two competing pathways are followed that branch at the Cys-alkylthiouronium ion intermediate. One pathway leads to direct formation of O-ureido-L-homoserine via a reactive thiouronium intermediate. The other pathway leads to an inactive form of the enzyme, which was shown by chemical model and mass spectrometric studies to be a Cys-alkylisothiourea adduct. This adduct undergoes slow hydrolysis to form O-ureido-L-homoserine and regenerated enzyme. In contrast, kinetic and mass spectrometric investigations demonstrate that the Cys-alkylthiouronium ion intermediate formed in the reaction of L-canavanine with Bacillus cereus ADI partitions between the product forming pathway (O-ureido-L-homoserine and free enzyme) and an inactivation pathway that leads to a stable Cys-alkylthiocarbamate adduct. The ADIs from Escherichia coli, Burkholderia mallei, and Giardia intestinalis were examined in order to demonstrate the generality of the L-canavanine slow substrate inhibition and to distinguish the kinetic behavior that defines the irreversible inhibition observed with the B. cereus ADI from the time controlled inhibition observed with the P. aeruginosa, E. coli, B. mallei, and G. intestinalis ADIs.

  10. The role of the irreversible electroporation in the hepato-pancreatico-biliary surgery.

    PubMed

    Sánchez-Velázquez, Patricia; Clavien, Pierre-Alain

    2017-03-16

    Irreversible electroporation is a novel technique growing in popularity over the last years among the ablative modalities. Its unique action mechanism produces irreversible nanopores in the membrane of the cell leading to apoptosis; therefore irreversible electroporation can be used to ablate substantial volumes of tissue without the undesirable thermal effects as the "heat sink effect". Moreover the extracellular matrix is left unperturbed, thus sparing the structural architecture of surrounding structures such as bile ducts and blood vessels. In the last years its use has been widespread in both liver and pancreatic ablation. Irreversible electroporation has shown its safety with however some caution, feasibility and favorable outcomes in clinical settings such as unresectable locally advanced disease in which the surgical and therapeutic options are very limited.

  11. Effect of design variables on irreversible magnet demagnetization in brushless dc motor

    NASA Astrophysics Data System (ADS)

    Kim, Tae Heoung; Lee, Ju

    2005-05-01

    The large demagnetizing currents in brushless dc (BLdc) motor are generated by the short-circuited stator windings and the fault of a drive circuit. So, irreversible magnet demagnetization occurs due to the external demagnetizing field by these currents. In this paper, we deal with the effect of design variables on irreversible magnet demagnetization in BLdc motor through the modeling approach using a two-dimensional finite-element method (2D FEM). The nonlinear analysis of a permanent magnet is added to 2D FEM to consider irreversible demagnetization. As a result, it is shown that magnet thickness, teeth surface width, and rotor back yoke thickness are the most important geometrical dimensions of BLdc motor in terms of irreversible magnet demagnetization.

  12. Reversible and irreversible structural transformations of nanocomponents of molecular layers by resonance photoexcitation or heating

    NASA Astrophysics Data System (ADS)

    Kaliteevskaya, Elena N.; Krutyakova, Valentina P.; Razumova, Tatyana K.; Starovoytov, Anton A.

    2010-09-01

    The reversible and irreversible structural transformations of monomolecular and associated nanocomponents of a polymethine dye layer by photoexcitation or heating are studied experimentally. The photo- and thermodestruction yields of the layers are investigated.

  13. Irreversible entropy production in two-phase flows with evaporating drops

    NASA Technical Reports Server (NTRS)

    Bellan, J.; Okong'o, N. A.

    2002-01-01

    A derivation of the irreversible entropy production, that is the dissipation, in two-phase flows is presented for the purpose of examining the effect of evaporative-drop modulation of flows having turbulent features.

  14. Ecological optimization of an irreversible quantum Carnot heat engine with spin-1/2 systems

    NASA Astrophysics Data System (ADS)

    Liu, Xiaowei; Chen, Lingen; Wu, Feng; Sun, Fengrui

    2010-02-01

    A model of a quantum heat engine with heat resistance, internal irreversibility and heat leakage and many non-interacting spin-1/2 systems is established in this paper. The quantum heat engine cycle is composed of two isothermal processes and two irreversible adiabatic processes and is referred to as a spin quantum Carnot heat engine. Based on the quantum master equation and the semi-group approach, equations of some important performance parameters, such as power output, efficiency, entropy generation rate and ecological function (a criterion representing the optimal compromise between exergy output rate and exergy loss rate), for the irreversible spin quantum Carnot heat engine are derived. The optimal ecological performance of the heat engine in the classical limit is analyzed with numerical examples. The effects of internal irreversibility and heat leakage on ecological performance are discussed in detail.

  15. The Effects of Internal and External Irreversibility of a Vapor Compression Refrigeration Cycle

    NASA Astrophysics Data System (ADS)

    Wang, Fu-Jen; Chiou, Jeng-Shing

    The concept of finite-time thermodynamics is employed to investigate the optimal refrigeration rate for an irreversible refrigeration cycle. The heat transfer between the system (internal) fluid and cooling (external) fluid takes place at the actual heat exchanger, which has the finite-size heat transfer area and the realistic heat transfer effectiveness. The internal irreversibility results from the compression process and the expansion process are also considered. The optimal refrigeration rate is calculated and expressed in terms of the irreversibility parameter (Ir), coefficient of performance (COP), the time ratio(γ) of heat transfer processes and the effectiveness of heat exchanger. The derived COP which consider both the external and internal irreversibility can thus be considered as the benchmark value for a practical refrigeration cycle, and the parametric study can provide the basis for both determination of optimal operating conditions and design of a practical refrigeration cycle.

  16. Thermal inactivation of Salmonella in peanut butter.

    PubMed

    Ma, Li; Zhang, Guodong; Gerner-Smidt, Peter; Mantripragada, Vijaya; Ezeoke, Ifeoma; Doyle, Michael P

    2009-08-01

    The objective of this study was to determine the rates of thermal inactivation of three Salmonella Tennessee strains in peanut butter associated with an outbreak and to compare them to the rates of inactivation of Salmonella strains of other serotypes (Enteritidis, Typhimurium, and Heidelberg) (SSOS) and of clinical isolates of Salmonella Tennessee from sporadic cases (STSC). Commercial peanut butter was inoculated with Salmonella isolates and heated at 71, 77, 83, and 90 degrees C. The thermal inactivation curves were upwardly concave, indicating rapid death at the beginning (20 min) of heating followed by lower death rates thereafter. The first-order kinetics approach and nonlinear Weibull model were used to fit the inactivation curves and describe the rates of thermal inactivation of Salmonella in peanut butter. The calculated minimum times needed to obtain a 7-log reduction at 90 degrees C for the composited three outbreak-associated strains were significantly greater (P < 0.05) than those of SSOS and STSC. Approximately 120 min were needed to reduce the outbreak strains of Salmonella Tennessee by 7 log, whereas 86 and 55 min were needed for SSOS and STSC, respectively. These results indicate that the outbreak-associated Salmonella strains were more thermotolerant than the other Salmonella strains tested, and this greater thermal resistance was not serotype specific. Thermal treatments of peanut butter at 90 degrees C for less than 30 min are not sufficient to kill large populations (5 log CFU/g) of Salmonella in highly contaminated peanut butter.

  17. Kinetics of Hydrothermal Inactivation of Endotoxins ▿

    PubMed Central

    Li, Lixiong; Wilbur, Chris L.; Mintz, Kathryn L.

    2011-01-01

    A kinetic model was established for the inactivation of endotoxins in water at temperatures ranging from 210°C to 270°C and a pressure of 6.2 × 106 Pa. Data were generated using a bench scale continuous-flow reactor system to process feed water spiked with endotoxin standard (Escherichia coli O113:H10). Product water samples were collected and quantified by the Limulus amebocyte lysate assay. At 250°C, 5-log endotoxin inactivation was achieved in about 1 s of exposure, followed by a lower inactivation rate. This non-log-linear pattern is similar to reported trends in microbial survival curves. Predictions and parameters of several non-log-linear models are presented. In the fast-reaction zone (3- to 5-log reduction), the Arrhenius rate constant fits well at temperatures ranging from 120°C to 250°C on the basis of data from this work and the literature. Both biphasic and modified Weibull models are comparable to account for both the high and low rates of inactivation in terms of prediction accuracy and the number of parameters used. A unified representation of thermal resistance curves for a 3-log reduction and a 3 D value associated with endotoxin inactivation and microbial survival, respectively, is presented. PMID:21193667

  18. Inactivated infectious haematopoietic necrosis virus (IHNV) vaccines.

    PubMed

    Anderson, E; Clouthier, S; Shewmaker, W; Weighall, A; LaPatra, S

    2008-10-01

    The inactivation dynamics of infectious haematopoietic necrosis virus (IHNV) by b-propiolactone (BPL), binary ethylenimine (BEI), formaldehyde or heat and the antigenic and immunogenic properties of the inactivated vaccines were evaluated. Chemical treatment of IHNV with 2.7 mm BPL, 1.5 mm BEI or 50 mm formaldehyde abolished virus infectivity within 48 h whereas heat treatment at 50 or 100 degrees C rendered the virus innocuous within 30 min. The inactivated IHNV vaccines were recognized by rainbow trout, Oncorhynchus mykiss, IHNV-specific antibodies and were differentially recognized by antigenic site I or antigenic site II IHNV glycoprotein-specific neutralizing monoclonal antibodies. The BPL inactivated whole virus vaccine was highly efficacious in vaccinated rainbow trout challenged by waterborne exposure to IHNV 7, 28, 42 or 56 days (15 degrees C) after immunization. The formaldehyde inactivated whole virus vaccine was efficacious 7 or 11 days after vaccination of rainbow trout but performed inconsistently when tested at later time points. The other vaccines tested were not efficacious.

  19. Genes that escape from X inactivation.

    PubMed

    Berletch, Joel B; Yang, Fan; Xu, Jun; Carrel, Laura; Disteche, Christine M

    2011-08-01

    To achieve a balanced gene expression dosage between males (XY) and females (XX), mammals have evolved a compensatory mechanism to randomly inactivate one of the female X chromosomes. Despite this chromosome-wide silencing, a number of genes escape X inactivation: in women about 15% of X-linked genes are bi-allelically expressed and in mice, about 3%. Expression from the inactive X allele varies from a few percent of that from the active allele to near equal expression. While most genes have a stable inactivation pattern, a subset of genes exhibit tissue-specific differences in escape from X inactivation. Escape genes appear to be protected from the repressive chromatin modifications associated with X inactivation. Differences in the identity and distribution of escape genes between species and tissues suggest a role for these genes in the evolution of sex differences in specific phenotypes. The higher expression of escape genes in females than in males implies that they may have female-specific roles and may be responsible for some of the phenotypes observed in X aneuploidy.

  20. Nucleophilic Additions to Coordinated 1,10-Phenanthroline: Intramolecular, Intermolecular, Reversible, and Irreversible.

    PubMed

    Arévalo, Rebeca; Menéndez, M Isabel; López, Ramón; Merino, Isabel; Riera, Lucía; Pérez, Julio

    2016-12-12

    KN(SiMe3 )2 reacts with [Re(CO)3 (phen)(PMe3 )]OTf via reversible addition to the phen ligand and irreversible deprotonation of the PMe3 ligand followed by intramolecular attack to phen by the deprotonated phosphane, whereas MeLi irreversibly adds to phen. The addition of MeLi has been shown to be intermolecular, unlike previously known nucleophilic additions to pyridines.

  1. From Dynamic Combinatorial Chemistry to in Vivo Evaluation of Reversible and Irreversible Myeloperoxidase Inhibitors.

    PubMed

    Soubhye, Jalal; Gelbcke, Michel; Van Antwerpen, Pierre; Dufrasne, François; Boufadi, Mokhtaria Yasmina; Nève, Jean; Furtmüller, Paul G; Obinger, Christian; Zouaoui Boudjeltia, Karim; Meyer, Franck

    2017-02-09

    The implementation of dynamic combinatorial libraries allowed the determination of highly active reversible and irreversible inhibitors of myeloperoxidase (MPO) at the nanomolar level. Docking experiments highlighted the interaction between the most active ligands and MPO, and further kinetic studies defined the mode of inhibition of these compounds. Finally, in vivo evaluation showed that one dose of irreversible inhibitors is able to suppress the activity of MPO after inducing inflammation.

  2. Kinetics of calcium-dependent inactivation of calcium current in voltage-clamped neurones of Aplysia californica.

    PubMed Central

    Chad, J; Eckert, R; Ewald, D

    1984-01-01

    Ca currents flowing during voltage-clamp depolarizations were examined in axotomized Aplysia neurones under conditions that virtually eliminated other currents. Moderate to large currents exhibited a two-component time course of relaxation that can be approximated reasonably well by the sum of two exponentials. The rapid phase (tau 1 approximately equal to 70 ms at 0 mV) plus the slower phase (tau 2 approximately equal to 300 ms at 0 mV) ride upon a steady, non-inactivating current, I infinity. Conditions that diminish the peak current amplitude, such as reduced stimulus depolarization, inactivation remaining from a prior depolarization, or partial blockade of the Ca conductance by Cd, slowed both phases of inactivation, and all selectively eliminated the tau 1 phase, such that weak currents exhibited only the slower phase of decline. Injection of EGTA slowed both phases of inactivation, decreased the extent of the tau 1 phase, and increased the intensity of I infinity and of the current during the tau 2 phase. For a given voltage, the rate of inactivation increased as the peak current strength was increased, and decreased as the peak current strength was decreased. For a given peak current the rate of inactivation decreased as depolarization was increased. The relation of inactivation to prior Ca2+ entry was essentially linear for small currents, but decreased in slope with time during strong currents. The relation also became shallower with increasing depolarization, suggesting an apparent decrease in the efficacy of Ca in causing inactivation at more positive potentials. The basic kinetics of Ca current inactivation along with experimentally induced changes in those kinetics were simulated with a binding-site model in which inactivation develops during current flow as a function of the entry and accumulation of free Ca2+. This demonstrated that a single Ca-mediated process can account for the two-component time course of inactivation, and that the nearly bi

  3. Structural basis for the coupling between activation and inactivation gates in K(+) channels.

    PubMed

    Cuello, Luis G; Jogini, Vishwanath; Cortes, D Marien; Pan, Albert C; Gagnon, Dominique G; Dalmas, Olivier; Cordero-Morales, Julio F; Chakrapani, Sudha; Roux, Benoît; Perozo, Eduardo

    2010-07-08

    The coupled interplay between activation and inactivation gating is a functional hallmark of K(+) channels. This coupling has been experimentally demonstrated through ion interaction effects and cysteine accessibility, and is associated with a well defined boundary of energetically coupled residues. The structure of the K(+) channel KcsA in its fully open conformation, in addition to four other partial channel openings, richly illustrates the structural basis of activation-inactivation gating. Here, we identify the mechanistic principles by which movements on the inner bundle gate trigger conformational changes at the selectivity filter, leading to the non-conductive C-type inactivated state. Analysis of a series of KcsA open structures suggests that, as a consequence of the hinge-bending and rotation of the TM2 helix, the aromatic ring of Phe 103 tilts towards residues Thr 74 and Thr 75 in the pore-helix and towards Ile 100 in the neighbouring subunit. This allows the network of hydrogen bonds among residues Trp 67, Glu 71 and Asp 80 to destabilize the selectivity filter, allowing entry to its non-conductive conformation. Mutations at position 103 have a size-dependent effect on gating kinetics: small side-chain substitutions F103A and F103C severely impair inactivation kinetics, whereas larger side chains such as F103W have more subtle effects. This suggests that the allosteric coupling between the inner helical bundle and the selectivity filter might rely on straightforward mechanical deformation propagated through a network of steric contacts. Average interactions calculated from molecular dynamics simulations show favourable open-state interaction-energies between Phe 103 and the surrounding residues. We probed similar interactions in the Shaker K(+) channel where inactivation was impaired in the mutant I470A. We propose that side-chain rearrangements at position 103 mechanically couple activation and inactivation in KcsA and a variety of other K(+) channels.

  4. Carvacrol suppresses high pressure high temperature inactivation of Bacillus cereus spores.

    PubMed

    Luu-Thi, Hue; Corthouts, Jorinde; Passaris, Ioannis; Grauwet, Tara; Aertsen, Abram; Hendrickx, Marc; Michiels, Chris W

    2015-03-16

    The inactivation of bacterial spores generally proceeds faster and at lower temperatures when heat treatments are conducted under high pressure, and high pressure high temperature (HPHT) processing is, therefore, receiving an increased interest from food processors. However, the mechanisms of spore inactivation by HPHT treatment are poorly understood, particularly at moderately elevated temperature. In the current work, we studied inactivation of the spores of Bacillus cereus F4430/73 by HPHT treatment for 5 min at 600MPa in the temperature range of 50-100°C, using temperature increments of 5°C. Additionally, we investigated the effect of the natural antimicrobial carvacrol on spore germination and inactivation under these conditions. Spore inactivation by HPHT was less than about 1 log unit at 50 to 70°C, but gradually increased at higher temperatures up to about 5 log units at 100°C. DPA release and loss of spore refractility in the spore population were higher at moderate (≤65°C) than at high (≥70°C) treatment temperatures, and we propose that moderate conditions induced the normal physiological pathway of spore germination resulting in fully hydrated spores, while at higher temperatures this pathway was suppressed and replaced by another mechanism of pressure-induced dipicolinic acid (DPA) release that results only in partial spore rehydration, probably because spore cortex hydrolysis is inhibited. Carvacrol strongly suppressed DPA release and spore rehydration during HPHT treatment at ≤65°C and also partly inhibited DPA release at ≥65°C. Concomitantly, HPHT spore inactivation was reduced by carvacrol at 65-90°C but unaffected at 95-100°C.

  5. Influence of membrane properties on physically reversible and irreversible fouling in membrane bioreactors.

    PubMed

    Tsuyuhara, T; Hanamoto, Y; Miyoshi, T; Kimura, K; Watanabe, Y

    2010-01-01

    This study aimed to examine the impact of membrane properties on membrane fouling in membrane bioreactor (MBR). Membrane fouling was divided into two categories: physically reversible and irreversible fouling. Membrane properties related to each type of membrane fouling were investigated separately. Five microfiltration (MF) and one ultrafiltration (UF) membranes with different properties (pore size, contact angle, roughness, zeta potential, and pure water permeability) were examined with a laboratory-scale MBR, fed with synthetic wastewater. Two separate experiments were conducted: the first to examine physically reversible fouling, and the second to examine physically irreversible fouling. The correlation between the degree of each type of fouling and membrane properties was studied. High correlation was observed between the degree of physically reversible fouling and roughness (R(2)=0.96). In contrast, with regard to physically irreversible fouling, strong correlation between roughness and degree of membrane fouling can only be found in the case of MF membranes. Except for the membrane with the highest roughness, the degree of physically irreversible fouling can be well correlated with pure water permeability (lower pure water permeability results in higher degree of physically irreversible fouling) including UF membrane. On the basis of the results obtained in this study, it can be concluded that roughness is an important factor in determination of physically reversible fouling regardless of the types of membrane (i.e. MF or UF membranes) and evolutions of physically irreversible fouling can be mitigated when an MBR is operated with membranes with smooth surface and high pure water permeability.

  6. Substance P and CGRP expression in dental pulps with irreversible pulpitis.

    PubMed

    Sattari, Mandana; Mozayeni, Mohammad Ali; Matloob, Arash; Mozayeni, Maryam; Javaheri, Homan H

    2010-08-01

    The purpose of this study was to compare substance P (SP) and calcitonin gene-related peptide (CGRP) expression in pulp tissue with clinically diagnosed symptomatic and asymptomatic irreversible pulpitis. Healthy pulps acted as controls. Five normal pulps and 40 with irreversible pulpitis (20 symptomatic and 20 asymptomatic) were obtained from 45 different patients. SP and CGRP expression was determined by competition binding assays using enzyme immunoassay. anova and Mann-Whitney tests were used to ascertain if there were statistically significant differences between the groups. The results showed that neuropeptides were found in all pulp samples. The highest and the lowest expressions for SP and CGRP were found in symptomatic irreversible pulpitis and healthy pulps groups, respectively. The differences between healthy pulps and the groups of pulps having irreversible pulpitis were significant (P < 0.001). Although Mann-Whitney's post-hoc tests showed statistically significant differences in CGRP expression between two pulpitis groups (P < 0.05), differences in SP expression between symptomatic and asymptomatic irreversible pulpitis groups were not significant. This study demonstrated that the expression of CGRP and SP is significantly higher in pulps with irreversible pulpitis compared with healthy pulps.

  7. Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma

    PubMed Central

    Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek

    2016-01-01

    Aim of the study Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Material and methods Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Results Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved – without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Conclusions Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM. PMID:27095938

  8. Theoretical foundations of apparent-damping phenomena and nearly irreversible energy exchange in linear conservative systems.

    PubMed

    Carcaterra, A; Akay, A

    2007-04-01

    This paper discusses a class of unexpected irreversible phenomena that can develop in linear conservative systems and provides a theoretical foundation that explains the underlying principles. Recent studies have shown that energy can be introduced to a linear system with near irreversibility, or energy within a system can migrate to a subsystem nearly irreversibly, even in the absence of dissipation, provided that the system has a particular natural frequency distribution. The present work introduces a general theory that provides a mathematical foundation and a physical explanation for the near irreversibility phenomena observed and reported in previous publications. Inspired by the properties of probability distribution functions, the general formulation developed here is based on particular properties of harmonic series, which form the common basis of linear dynamic system models. The results demonstrate the existence of a special class of linear nondissipative dynamic systems that exhibit nearly irreversible energy exchange and possess a decaying impulse response. In addition to uncovering a new class of dynamic system properties, the results have far-reaching implications in engineering applications where classical vibration damping or absorption techniques may not be effective. Furthermore, the results also support the notion of nearly irreversible energy transfer in conservative linear systems, which until now has been a concept associated exclusively with nonlinear systems.

  9. One- and two-dimensional quantum models: Quenches and the scaling of irreversible entropy.

    PubMed

    Sharma, Shraddha; Dutta, Amit

    2015-08-01

    Using the scaling relation of the ground state quantum fidelity, we propose the most generic scaling relations of the irreversible work (the residual energy) of a closed quantum system at absolute zero temperature when one of the parameters of its Hamiltonian is suddenly changed. We consider two extreme limits: the heat susceptibility limit and the thermodynamic limit. It is argued that the irreversible entropy generated for a thermal quench at low enough temperatures when the system is initially in a Gibbs state is likely to show a similar scaling behavior. To illustrate this proposition, we consider zero-temperature and thermal quenches in one-dimensional (1D) and 2D Dirac Hamiltonians where the exact estimation of the irreversible work and the irreversible entropy is possible. Exploiting these exact results, we then establish the following. (i) The irreversible work at zero temperature shows an appropriate scaling in the thermodynamic limit. (ii) The scaling of the irreversible work in the 1D Dirac model at zero temperature shows logarithmic corrections to the scaling, which is a signature of a marginal situation. (iii) Remarkably, the logarithmic corrections do indeed appear in the scaling of the entropy generated if the temperature is low enough while they disappear for high temperatures. For the 2D model, no such logarithmic correction is found to appear.

  10. Evaluation of properties of irreversible hydrocolloid impression materials mixed with disinfectant liquids

    PubMed Central

    Amalan, Arul; Ginjupalli, Kishore; Upadhya, Nagaraja

    2013-01-01

    Background: Addition of disinfectant to irreversible hydrocolloid impression materials can eliminate the disinfection step to avoid dimensional changes associated with it. The aim of the present study was to evaluate the effect of various disinfectant mixing liquids on the properties of commercially available irreversible hydrocolloid impression materials. Materials and Methods: Four commercially available irreversible hydrocolloid impression materials (Zelgan, Vignette, Tropicalgin, and Algitex) were mixed with disinfectant liquid containing chlorhexidine (0.1 and 0.2%) and sodium hypochlorite (0.1 and 0.5%). After mixing with disinfectant liquids, materials were evaluated for pH changes during gelation, gelation time, flow, gel strength, permanent deformation and detail reproduction. Results: Significant changes in gelation time were observed in irreversible hydrocolloid impression materials upon mixing with disinfectant liquids. In general, chlorhexidine increased the gelation time, whereas sodium hypochlorite reduced it. However, no significant changes in the flow were observed both with chlorhexidine and sodium hypochlorite. Gel strength was found to decrease when mixed with chlorhexidine, whereas an increase in gel strength was observed upon mixing with sodium hypochlorite. Permanent deformation of the most irreversible hydrocolloid impression materials was below the specification limit even after mixing with disinfectant liquids. Sodium hypochlorite significantly reduced the surface detail reproduction, whereas no change in detail reproduction was observed with chlorhexidine. Conclusion: Chlorhexidine solution can be used to mix irreversible hydrocolloid impression materials in regular dental practice as it did not significantly alter the properties. This may ensure effective disinfection of impressions. PMID:23878566

  11. Role of oxyradicals in the inactivation of catalase by ozone

    SciTech Connect

    Whiteside, C.; Hassan, H.M. )

    1988-01-01

    The antioxidant enzymes, catalase and superoxide dismutase, are inactivated upon exposure to ozone. In this study, the mechanism of this inactivation was examined using catalase as a model system. The data show that the inactivation of catalase is dependent on ozone concentration, time of exposure, and pH. Loss of catalase activity is accompanied with loss of the heme spectra. Tiron, desferal-Mn, trolox-c, and pyruvate protect the enzyme against ozone inactivation. SOD is less effective due to its inactivation by ozone. On the other hand, alcohols do not provide significant protection. The data suggest the possible involvement of superoxide radicals in the inactivation of catalase by ozone.

  12. Role of oxyradicals in the inactivation of catalase by ozone.

    PubMed

    Whiteside, C; Hassan, H M

    1988-01-01

    The antioxidant enzymes, catalase and superoxide dismutase, are inactivated upon exposure to ozone. In this study, the mechanism of this inactivation was examined using catalase as a model system. The data show that the inactivation of catalase is dependent on ozone concentration, time of exposure, and pH. Loss of catalase activity is accompanied with loss of the heme spectra. Tiron, desferal-Mn, trolox-c, and pyruvate protect the enzyme against ozone inactivation. SOD is less effective due to its inactivation by ozone. On the other hand, alcohols do not provide significant protection. The data suggest the possible involvement of superoxide radicals in the inactivation of catalase by ozone.

  13. Mechanism of enteroviral inactivation by ozone

    SciTech Connect

    Roy, D.; Wong, P.K.; Engelbrecht, R.S.; Chian, E.S.

    1981-03-01

    The mechanism of enteroviral inactivation by ozone was investigated with poliovirus 1 (Mahoney) as the model virus. Ozone was observed to alter two of the four polypeptide chains present in the viral protein coat of poliovirus 1. However, the alteration of the protein coat did not significantly impair virus adsorption or alter the integrity of the virus particle. Damage to the viral RNA after exposure to ozone was demonstrated by velocity sedimentation analysis. It was concluded that the damage to the viral nucleic acid is the major cause of poliovirus 1 inactivation by ozone.

  14. Mechanism of enteroviral inactivation by ozone.

    PubMed Central

    Roy, D; Wong, P K; Engelbrecht, R S; Chian, E S

    1981-01-01

    The mechanism of enteroviral inactivation by ozone was investigated with poliovirus 1 (Mahoney) as the model virus. Ozone was observed to alter two of the four polypeptide chains present in the viral protein coat of poliovirus 1. However, the alteration of the protein coat did not significantly impair virus adsorption or alter the integrity of the virus particle. Damage to the viral RNA after exposure to ozone was demonstrated by velocity sedimentation analysis. It was concluded that the damage to the viral nucleic acid is the major cause of poliovirus 1 inactivation by ozone. PMID:6261692

  15. Quality control of Photosystem II: reversible and irreversible protein aggregation decides the fate of Photosystem II under excessive illumination

    PubMed Central

    Yamamoto, Yasusi; Hori, Haruka; Kai, Suguru; Ishikawa, Tomomi; Ohnishi, Atsuki; Tsumura, Nodoka; Morita, Noriko

    2013-01-01

    In response to excessive light, the thylakoid membranes of higher plant chloroplasts show dynamic changes including the degradation and reassembly of proteins, a change in the distribution of proteins, and large-scale structural changes such as unstacking of the grana. Here, we examined the aggregation of light-harvesting chlorophyll-protein complexes and Photosystem II core subunits of spinach thylakoid membranes under light stress with 77K chlorophyll fluorescence; aggregation of these proteins was found to proceed with increasing light intensity. Measurement of changes in the fluidity of thylakoid membranes with fluorescence polarization of diphenylhexatriene showed that membrane fluidity increased at a light intensity of 500–1,000 μmol photons m-2 s-1, and decreased at very high light intensity (1,500 μmol photons m-2 s-1). The aggregation of light-harvesting complexes at moderately high light intensity is known to be reversible, while that of Photosystem II core subunits at extremely high light intensity is irreversible. It is likely that the reversibility of protein aggregation is closely related to membrane fluidity: increases in fluidity should stimulate reversible protein aggregation, whereas irreversible protein aggregation might decrease membrane fluidity. When spinach leaves were pre-illuminated with moderately high light intensity, the qE component of non-photochemical quenching and the optimum quantum yield of Photosystem II increased, indicating that Photosystem II/light-harvesting complexes rearranged in the thylakoid membranes to optimize Photosystem II activity. Transmission electron microscopy revealed that the thylakoids underwent partial unstacking under these light stress conditions. Thus, protein aggregation is involved in thylakoid dynamics and regulates photochemical reactions, thereby deciding the fate of Photosystem II. PMID:24194743

  16. Monolaurin and acetic acid inactivation of Listeria monocytogenes attached to stainless steel.

    PubMed

    Oh, D H; Marshall, D L

    1996-03-01

    Individual and combined antimicrobial effects of monolaurin and acetic acid on Listeria monocytogenes planktonic cells or stainless-steel-adherent cells were determined in order to evaluate cell viability during a 25-min exposure period at 25 degrees C. A 10(7)-colony-forming units (CFU)/ml population of planktonic cells was completely inactivated by the synergistic combination of 1% acetic acid with 50 or 100 microg/ml of monolaurin within 25 or 20 min, respectively. Either compound alone caused partial but incomplete inactivation within the same time periods. A population of 10(5) CFU/cm2 of 1-day adherent cells on stainless steel was completely inactivated within 25 min, but with the highest concentrations of the combined chemicals, i.e., 1% acetic acid and 100 microg/ml of monolaurin. The combined chemical treatment again synergistically produced greater inhibition. A 10(6)-CFU/cm2 population of 7-day adherent cells was not completely inactivated within 25 min of exposure, although counts did decline. The results demonstrate increased resistance of attached L. monocytogenes to acetic acid and monolaurin and show that resistance increased with culture age. Combinations of organic acids and monolaurin might be considered as sanitizers of food contact surfaces, but activities of such combinations are likely to be less than other commonly used sanitizers.

  17. Inactivation of F-specific bacteriophages during flocculation with polyaluminum chloride - a mechanistic study.

    PubMed

    Kreißel, Katja; Bösl, Monika; Hügler, Michael; Lipp, Pia; Franzreb, Matthias; Hambsch, Beate

    2014-03-15

    Bacteriophages are often used as surrogates for enteric viruses in spiking experiments to determine the efficiencies of virus removal of certain water treatment measures, like e.g. flocculation or filtration steps. Such spiking experiments with bacteriophages are indispensable if the natural virus concentrations in the raw water of water treatment plants are too low to allow the determination of elimination levels over several orders of magnitude. In order to obtain reliable results from such spiking tests, it is essential that bacteriophages behave comparable to viruses and remain stable during the experiments. To test this, the influence of flocculation parameters on the bacteriophages MS2, Qβ and phiX174 was examined. Notably, the F-specific phages MS2 and Qβ were found to be inactivated in flocculation processes with polyaluminum chloride (PACl). In contrast, other aluminum coagulants like AlCl3 or Al2(SO4)3 did not show a comparable effect on MS2 in this study. In experiments testing the influence of different PACl species on MS2 and Qβ inactivation during flocculation, it could be shown that cationic dissolved PACl species (Al13) interacted with the MS2 surface and hereby reduced the surviving phage fraction to c/c0 values below 1*10(-4) even at very low PACl concentrations of 7 μmol Al/L. Other inactivation mechanisms like the irreversible adsorption of phages to the floc structure or the damage of phage surfaces due to entrapment into the floc during coagulation and floc formation do not seem to contribute to the low surviving fraction found for both F-specific bacteriophages. Furthermore, no influence of phage agglomeration or pH drops during the flocculation process on phage inactivation could be observed. The somatic coliphage phiX174 in contrast did not show sensitivity to chemical stress and in accordance only slight interaction between Al13 and the phage surface was observed. Consequently, F-specific phages like MS2 should not be used as

  18. Inactivation of Bacillus atrophaeus by OH radicals

    NASA Astrophysics Data System (ADS)

    Ono, Ryo; Yonetamari, Kenta; Tokumitsu, Yusuke; Yonemori, Seiya; Yasuda, Hachiro; Mizuno, Akira

    2016-08-01

    The inactivation of Bacillus atrophaeus by OH radicals is measured. This study aims to evaluate the bactericidal effects of OH radicals produced by atmospheric-pressure nonthermal plasma widely used for plasma medicine; however, in this study, OH radicals are produced by vacuum ultraviolet (VUV) photolysis of water vapor instead of plasma to allow the production of OH radicals with almost no other reactive species. A 172 nm VUV light from a Xe2 excimer lamp irradiates a He-H2O mixture flowing in a quartz tube to photodissociate H2O to produce OH, H, O, HO2, H2O2, and O3. The produced reactive oxygen species (ROS) flow out of the quartz tube nozzle to the bacteria on an agar plate and cause inactivation. The inactivation by OH radicals among the six ROS is observed by properly setting the experimental conditions with the help of simulations calculating the ROS densities. A 30 s treatment with approximately 0.1 ppm OH radicals causes visible inactivation.

  19. Inactivation of plasminogen activator inhibitor by oxidants

    SciTech Connect

    Lawrence, D.A.; Loskutoff, D.J.

    1986-10-21

    The rapidly acting plasminogen activator inhibitor (PAI) purified from cultured bovine endothelial cells (BAEs) was inactivated during iodination with chloramine T and other oxidizing iodination systems. Inactivation was observed in the absence of iodine, suggesting that the loss of activity resulted from the oxidizing conditions employed. In an attempt to further study the nature of this inactivation, the PAI was treated with chloramine T under conditions that specifically oxidize methionine and cystein residues. Both PAI inhibitory activity and the ability of the PAI to form complexes with tissue-type PA were decreased in a dose-dependent manner by such treatment. PAI activity was measured with the lysis of /sup 125/I-labelled fibrin. The reductase is a DTT-dependent enzyme that specifically converts methionine sulfoxide to methionine. Little activity was restored by either the reductase or DTT alone. These results indicate that the oxidation of at least one critical methionine residue is responsible for the loss of PAI activity upon iodination. In this respect, the BAE PAI resembles ..cap alpha../sub 1/-protease inhibitor, a well-characterized elastase inhibitor that also is inactivated by oxidants. Both inhibitors are members of the serine protease inhibitor superfamily (Serpins), and both have a methionine residue in their reactive center.

  20. Bell's palsy and parenteral inactivated influenza vaccine.

    PubMed

    Stowe, Julia; Andrews, Nick; Wise, Lesley; Miller, Elizabeth

    2006-01-01

    Concern about a possible increased risk of Bell's palsy after parenteral inactivated influenza vaccine was raised following the publication in 2004 of a Swiss study in which there was an increased risk following the nasal inactivated formulation of the vaccine. When data from passive reporting systems in the United States and the United Kingdom were examined there was some evidence of increased reporting following the parenteral vaccine. A large population based study using the General Practice Research Database (GPRD) was therefore performed to test the hypothesis that there was an increased risk of Bell's palsy in the three months following parenteral inactivated influenza vaccine. The risk was also assessed for the same period following pneumococcal vaccine and was stratified into three age groups (<45, 45-64 and 65+ years). Relative incidence (RI) estimates were calculated using the self-controlled case-series method and showed no evidence of an increased risk in the three months following parenteral inactivated influenza vaccine RI 0.92 (95% confidence interval 0.78-1.08). There was also no evidence of an increased risk in any age group or following pneumococcal vaccine. A significant increase was seen on the day of vaccination (day 0) probably due to opportunistic recording of cases.

  1. Monochloramine inactivation of bacterial select agents.

    PubMed

    Rose, Laura J; Rice, Eugene W; Hodges, Lisa; Peterson, Alicia; Arduino, Matthew J

    2007-05-01

    Seven species of bacterial select agents were tested for susceptibility to monochloramine. Under test conditions, the monochloramine routinely maintained in potable water would reduce six of the species by 2 orders of magnitude within 4.2 h. Bacillus anthracis spores would require up to 3.5 days for the same inactivation with monochloramine.

  2. Inactivation of human norovirus using chemical sanitizers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The porcine gastric mucin binding magnetic bead (PGM-MB) assay was used to evaluate the ability of chlorine, chlorine dioxide, peroxyacetic acid, hydrogen peroxide, and trisodium phosphate to inactivate human norovirus within 10 percent stool filtrate. One min free chlorine treatments at concentrat...

  3. Inactivation of human interferon by body fluids

    NASA Technical Reports Server (NTRS)

    Cesario, T. C.; Mandell, A.; Tilles, J. G.

    1973-01-01

    Description of the effects of human feces, bile, saliva, serum, and cerebrospinal fluid on interferon activity. It is shown that crude interferon is inactivated by at least 50% more than with the control medium used, when incubated for 4 hr in vitro in the presence of serum, saliva, or cerebrospinal liquid, and by close to 100% when incubated with stool extract or bile.

  4. High Pressure Inactivation of HAV within Mussels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The potential of hepatitis A virus (HAV) to be inactivated within Mediterranean mussels (Mytilus galloprovincialis) and blue mussels (Mytilus edulis) by high pressure processing was evaluated. HAV was bioaccumulated within mussels to approximately 6-log10 PFU by exposure of mussels to HAV-contamina...

  5. Sex chromosome inactivation in the male.

    PubMed

    Yan, Wei; McCarrey, John R

    2009-10-01

    Mammalian females have two X chromosomes, while males have only one X plus a Y chromosome. In order to balance X-linked gene dosage between the sexes, one X chromosome undergoes inactivation during development of female embryos. This process has been termed X-chromosome inactivation (XCI). Inactivation of the single X chromosome also occurs in the male, but is transient and is confined to the late stages of first meiotic prophase during spermatogenesis. This phenomenon has been termed meiotic sex chromosome inactivation (MSCI). A substantial portion ( approximately 15-25%) of X-linked mRNA-encoding genes escapes XCI in female somatic cells. While no mRNA genes are known to escape MSCI in males, approximately 80% of X-linked miRNA genes have been shown to escape this process. Recent results have led to the proposal that the RNA interference mechanism may be involved in regulating XCI in female cells. We suggest that some MSCI-escaping miRNAs may play a similar role in regulating MSCI in male germ cells.

  6. Bioinactivation: Software for modelling dynamic microbial inactivation.

    PubMed

    Garre, Alberto; Fernández, Pablo S; Lindqvist, Roland; Egea, Jose A

    2017-03-01

    This contribution presents the bioinactivation software, which implements functions for the modelling of isothermal and non-isothermal microbial inactivation. This software offers features such as user-friendliness, modelling of dynamic conditions, possibility to choose the fitting algorithm and generation of prediction intervals. The software is offered in two different formats: Bioinactivation core and Bioinactivation SE. Bioinactivation core is a package for the R programming language, which includes features for the generation of predictions and for the fitting of models to inactivation experiments using non-linear regression or a Markov Chain Monte Carlo algorithm (MCMC). The calculations are based on inactivation models common in academia and industry (Bigelow, Peleg, Mafart and Geeraerd). Bioinactivation SE supplies a user-friendly interface to selected functions of Bioinactivation core, namely the model fitting of non-isothermal experiments and the generation of prediction intervals. The capabilities of bioinactivation are presented in this paper through a case study, modelling the non-isothermal inactivation of Bacillus sporothermodurans. This study has provided a full characterization of the response of the bacteria to dynamic temperature conditions, including confidence intervals for the model parameters and a prediction interval of the survivor curve. We conclude that the MCMC algorithm produces a better characterization of the biological uncertainty and variability than non-linear regression. The bioinactivation software can be relevant to the food and pharmaceutical industry, as well as to regulatory agencies, as part of a (quantitative) microbial risk assessment.

  7. Heat Inactivation of Human Pathogens on Catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the National Advisory Committee on Microbiological Criteria for Food (NACMCF) determined that the cooking (time/temperature) for finfish would be different than for meat products and identified a need for time/temperature requirements to assure the thermal inactivation of the human pathogens: Sa...

  8. Inactivation of Listeria monocytogenes on catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes, a psychrotrophic foodborne pathogen, is an occasional post-process contaminant on retail catfish. In this study, bacteriophages were evaluated for the ability to inactivate a cocktail of L. monocytogenes inoculated (4-5 log cfu/cm2) onto raw catfish. Spray application of bac...

  9. Oxidative inactivation of an extramitochondrial acetyl-CoA hydrolase by autoxidation of L-ascorbic acid.

    PubMed

    Nakanishi, Y; Isohashi, F; Matsunaga, T; Sakamoto, Y

    1985-10-15

    The activity of acetyl-CoA hydrolase (dimeric form) purified from the supernatant fraction of rat liver was shown to have a half-life (t1/2) of 3 min at 0 degree C, but to stable at 37 degrees C (t1/2 = 34 h) [Isohashi, F., Nakanishi, Y. & Sakamoto, Y. (1983) Biochemistry 22, 584-590]. Incubation of the purified enzyme with L-ascorbic acid (AsA) at 37 degrees C resulted in inactivation of the enzyme (t1/2 = 90 min at 2 mM AsA). The extent of inactivation was greatly enhanced by addition of transition metal ions (Cu2+, Fe2+, and Fe3+). Thiol reducing agents, such as reduced glutathione and DL-dithiothreitol, protected the hydrolase from inactivation by AsA. However, these materials did not restore the catalytic activity of the enzyme inactivated by AsA. When AsA solution containing Cu2+ was preincubated under aerobic conditions at 37 degrees C for various times in the absence of enzyme, and then aliquots were incubated with the enzyme solution for 20 min, remaining activity was found to decrease with increase in the preincubation time, reaching a minimum at 60 min. However, further preincubation reduced the potential for inactivation. Catalase, a hydrogen peroxide (H2O2) scavenger, almost completely prevented inactivation of the enzyme by AsA plus Cu2+. Superoxide dismutase and tiron, which are both superoxide (O2-) scavengers, also prevented inactivation of the enzyme. A high concentration of mannitol, a hydroxyl radical (OH) scavenger, partially protected the enzyme from inactivation. These results suggest that inactivation of the enzyme by AsA in the presence of Cu2+ was due to the effect of active oxygen species (H2O2, O2-, OH) that are known to be autoxidation products of AsA. Valeryl-CoA, a competitive inhibitor of acetyl-CoA hydrolase, greatly protected the enzyme from inactivation by AsA plus Cu2+, but ATP and ADP, which are both effectors of this enzyme, had only slight protective effects. These results suggest that inactivation of this enzyme by addition

  10. Radiation-induced inactivation of enzymes - Molecular mechanism based on inactivation of dehydrogenases

    NASA Astrophysics Data System (ADS)

    Rodacka, Aleksandra; Gerszon, Joanna; Puchala, Mieczyslaw; Bartosz, Grzegorz

    2016-11-01

    Proteins, which have enzymatic activities play a fundamental role in the cell due to participation in most of biological processes. Oxidative-induced damage of enzymes often have marked effects on cellular processes, which in consequence determine cell functioning and survival. In this review, we focused on the radiation-induced inactivation of enzymes with particular emphasis on the inactivation of dehydrogenases. For a better understanding of this issue, the efficiency of products of water radiolysis (•OH, O2•- and H2O2) in enzyme inactivation has been analysed. Reactions of reactive oxygen species (ROS) with amino acids present in the active site of enzymes appear to have the greatest impact on enzyme inactivation.

  11. The antibrowning agent sulfite inactivates Agaricus bisporus tyrosinase through covalent modification of the copper-B site.

    PubMed

    Kuijpers, Tomas F M; Gruppen, Harry; Sforza, Stefano; van Berkel, Willem J H; Vincken, Jean-Paul

    2013-12-01

    Sulfite salts are widely used as antibrowning agents in food processing. Nevertheless, the exact mechanism by which sulfite prevents enzymatic browning has remained unknown. Here, we show that sodium hydrogen sulfite (NaHSO3) irreversibly blocks the active site of tyrosinase from the edible mushroom Agaricus bisporus, and that the competitive inhibitors tropolone and kojic acid protect the enzyme from NaHSO3 inactivation. LC-MS analysis of pepsin digests of NaHSO3 -treated tyrosinase revealed two peptides showing a neutral loss corresponding to the mass of SO3 upon MS(2) fragmentation. These peptides were found to be homologous peptides containing two of the three histidine residues that form the copper-B-binding site of mushroom tyrosinase isoform PPO3 and mushroom tyrosinase isoform PPO4, which were both present in the tyrosinase preparation used. Peptides showing this neutral loss behavior were not found in the untreated control. Comparison of the effects of NaHSO3 on apo-tyrosinase and holo-tyrosinase indicated that inactivation is facilitated by the active site copper ions. These data provide compelling evidence that inactivation of mushroom tyrosinase by NaHSO3 occurs through covalent modification of a single amino-acid residue, probably via addition of HSO3(-) to one of the copper-coordinating histidines in the copper-B site of the enzyme.

  12. The Transient Inactivation of the Master Cell Cycle Phosphatase Cdc14 Causes Genomic Instability in Diploid Cells of Saccharomyces cerevisiae

    PubMed Central

    Quevedo, Oliver; Ramos-Pérez, Cristina; Petes, Thomas D.; Machín, Félix

    2015-01-01

    Genomic instability is a common feature found in cancer cells . Accordingly, many tumor suppressor genes identified in familiar cancer syndromes are involved in the maintenance of the stability of the genome during every cell division and are commonly referred to as caretakers. Inactivating mutations and epigenetic silencing of caretakers are thought to be the most important mechanisms that explain cancer-related genome instability. However, little is known of whether transient inactivation of caretaker proteins could trigger genome instability and, if so, what types of instability would occur. In this work, we show that a brief and reversible inactivation, during just one cell cycle, of the key phosphatase Cdc14 in the model organism Saccharomyces cerevisiae is enough to result in diploid cells with multiple gross chromosomal rearrangements and changes in ploidy. Interestingly, we observed that such transient loss yields a characteristic fingerprint whereby trisomies are often found in small-sized chromosomes, and gross chromosome rearrangements, often associated with concomitant loss of heterozygosity, are detected mainly on the ribosomal DNA-bearing chromosome XII. Taking into account the key role of Cdc14 in preventing anaphase bridges, resetting replication origins, and controlling spindle dynamics in a well-defined window within anaphase, we speculate that the transient loss of Cdc14 activity causes cells to go through a single mitotic catastrophe with irreversible consequences for the genome stability of the progeny. PMID:25971663

  13. Photocatalytic inactivation of Escherichia coli by natural sphalerite suspension: effect of spectrum, wavelength and intensity of visible light.

    PubMed

    Chen, Yanmin; Lu, Anhuai; Li, Yan; Yip, Ho Yin; An, Taicheng; Li, Guiying; Jin, Peng; Wong, Po-Keung

    2011-08-01

    The photocatalytic disinfection of Escherichia coli K-12 is investigated by the natural sphalerite (NS) under different spectra, wavelengths and intensities of visible light (VL) emitted by light-emitting-diode lamp (LED). The spectrum effect of VL on disinfection efficiency is studied by using white LED, fluorescent tube (FT) and xenon lamp (XE), which indicates that the "discreted peak spectrum" of FT is more effective to inactivate bacteria than "continuous spectrum" of LED and XE. Besides, the photocatalytic disinfection of bacteria is compared under different single spectrum (blue, green, yellow and red color) LEDs. The results show that the most effective wavelength ranges of VL for photocatalytic disinfection with the NS are 440-490 and 570-620 nm. Furthermore, a positive relationship is obtained between the disinfection efficiency and the VL intensity. The experiment shows that NS can completely inactivate 10(7)cfu mL(-1)E. coli K-12 within 8h irradiation by white LED with the intensity of 200 mW cm(-2) at pH 8. Moreover, the destruction process of the cell wall and the cell membrane are directly observed by TEM. Finally, no bacterial colony can be detected within a 96 h regrowth test of inactivated bacteria, which reveals that the VL-photocatalytic disinfection leads to an irreversible damage to the bacterial cells.

  14. The Transient Inactivation of the Master Cell Cycle Phosphatase Cdc14 Causes Genomic Instability in Diploid Cells of Saccharomyces cerevisiae.

    PubMed

    Quevedo, Oliver; Ramos-Pérez, Cristina; Petes, Thomas D; Machín, Félix

    2015-07-01

    Genomic instability is a common feature found in cancer cells . Accordingly, many tumor suppressor genes identified in familiar cancer syndromes are involved in the maintenance of the stability of the genome during every cell division and are commonly referred to as caretakers. Inactivating mutations and epigenetic silencing of caretakers are thought to be the most important mechanisms that explain cancer-related genome instability. However, little is known of whether transient inactivation of caretaker proteins could trigger genome instability and, if so, what types of instability would occur. In this work, we show that a brief and reversible inactivation, during just one cell cycle, of the key phosphatase Cdc14 in the model organism Saccharomyces cerevisiae is enough to result in diploid cells with multiple gross chromosomal rearrangements and changes in ploidy. Interestingly, we observed that such transient loss yields a characteristic fingerprint whereby trisomies are often found in small-sized chromosomes, and gross chromosome rearrangements, often associated with concomitant loss of heterozygosity, are detected mainly on the ribosomal DNA-bearing chromosome XII. Taking into account the key role of Cdc14 in preventing anaphase bridges, resetting replication origins, and controlling spindle dynamics in a well-defined window within anaphase, we speculate that the transient loss of Cdc14 activity causes cells to go through a single mitotic catastrophe with irreversible consequences for the genome stability of the progeny.

  15. Rapidly inactivating and non-inactivating calcium-activated potassium currents in frog saccular hair cells

    PubMed Central

    Armstrong, Cecilia E; Roberts, William M

    2001-01-01

    Using a semi-intact epithelial preparation we examined the Ca2+-activated K+ (KCa) currents of frog (Rana pipiens) saccular hair cells. After blocking voltage-dependent K+ (KV) currents with 4-aminopyridine (4-AP) an outward current containing inactivating (Itransient) and non-inactivating (Isteady) components remained.The contribution of each varied greatly from cell to cell, with Itransient contributing from 14 to 90 % of the total outward current. Inactivation of Itransient was rapid (τ≈ 2–3 ms) and occurred within the physiological range of membrane potentials (V1/2=−63 mV). Recovery from inactivation was also rapid (τ≈ 10 ms).Suppression of both Itransient and Isteady by depolarizations that approached the Ca2+ equilibrium potential and by treatments that blocked Ca2+ influx (application Ca2+-free saline or Cd2+), suggest both are Ca2+ dependent. Both were blocked by iberiotoxin, a specific blocker of large-conductance KCa channels (BK), but not by apamin, a specific blocker of small-conductance KCa channels.Ensemble-variance analysis showed that Itransient and Isteady flow through two distinct populations of channels, both of which have a large single-channel conductance (∼100 pS in non-symmetrical conditions). Together, these data indicate that both Itransient and Isteady are carried through BK channels, one of which undergoes rapid inactivation while the other does not.Inactivation of Itransient could be removed by extracellular papain and could later be restored by intracellular application of the ‘ball’ domain of the auxiliary subunit (β2) thought to mediate BK channel inactivation in rat chromaffin cells. We hypothesize that Itransient results from the association of a similar β subunit with some of the BK channels and that papain removes inactivation by cleaving extracellular sites required for this association. PMID:11579156

  16. Functional inactivation of Rb sensitizes cancer cells to TSC2 inactivation induced cell death.

    PubMed

    Danos, Arpad M; Liao, Yang; Li, Xuan; Du, Wei

    2013-01-01

    We showed previously that inactivation of TSC2 induces death in cancer cells lacking the Retinoblastoma (Rb) tumor suppressor under stress conditions, suggesting that inactivation of TSC2 can potentially be used as an approach to specifically kill cancers that have lost WT Rb. As Rb is often inactivated in cancers by overexpression of cyclin D1, loss of p16(ink4a) cdk inhibitor, or expression of viral oncoproteins, it will be interesting to determine if such functional inactivation of Rb would similarly sensitize cancer cells to TSC2 inactivation induced cell death. In addition, many cancers lack functional Pten, resulting in increased PI3K/Akt signaling that has been shown to modulate E2F-induced cell death. Therefore it will be interesting to test whether loss of Pten will affect TSC2 inactivation induced killing of Rb mutant cancer cells. Here, we show that overexpression of Cyclin D1 or the viral oncogene E1a sensitizes cancer cells to TSC2 knockdown induced cell death and growth inhibition. On the other hand, knockdown of p16(ink4a) sensitizes cancer cells to TSC2 knockdown induced cell death in a manner that is likely dependant on serum induction of Cyclin D1 to inactivate the Rb function. Additionally, we demonstrate that loss of Pten does not interfere with TSC2 knockdown induced cell death in Rb mutant cancer cells. Together, these results suggest that TSC2 is potentially a useful target for a large spectrum of cancer types with an inactivated Rb pathway.

  17. Photo-inactivation of Bacillus endospores: inter-specific variability of inactivation efficiency.

    PubMed

    da Silva, Raquel N; Tomé, Augusto C; Tomé, João P C; Neves, Maria G P M S; Faustino, Maria A F; Cavaleiro, José A S; Oliveira, Anabela; Almeida, Adelaide; Cunha, Ângela

    2012-10-01

    The aims of this work were to (a) evaluate the susceptibility of endospores of Bacillus cereus, B. licheniformis, B. sphaericus and B. subtilis to photodynamic inactivation using a tricationic porphyrin as photosensitizer, (b) assess the efficiency of adsorption of the photosensitizer in endospore material as a determinant of the susceptibility of endospores of different Bacillus species to photo-inactivation, (c) determine the value of B. cereus as a model organism for studies of antimicrobial photodynamic inactivation of bacterial endospores. The results of irradiation experiments with endospores of four species of Bacillus showed that B. cereus was the only species for which efficient endospore photo-inactivation (> 3 log reduction) could be achieved. Endospores of B. licheniformis, B. sphaericus and B. subtilis were virtually resistant to photo-inactivation with tricationic porphyrin. The amount of porphyrin bound to endospore material was not significantly different between species, regardless of the presence of an exosporium or exosporium-like outer layer. The sensitivity of endospores to photodynamic inactivation with a tricationic porphyrin is highly variable among different species of the genus Bacillus. The presence of an exosporium in endospores of B. cereus and B. sphaericus, or an exosporium-like glycoprotein layer in endospores of B. subtilis, did not affect the amount of bound photosensitizer and did not explain the inter-species variability in susceptibility to photodynamic inactivation. The results imply that the use of B. cereus as a more amenable surrogate of the exosporium-producing B. anthracis must be carefully considered when testing new photosensitizers for their antimicrobial photo-inactivation properties.

  18. Health Technology Assessment of CEM Pulpotomy in Permanent Molars with Irreversible Pulpitis

    PubMed Central

    Yazdani, Shahram; Jadidfard, Mohammad-Pooyan; Tahani, Bahareh; Kazemian, Ali; Dianat, Omid; Alim Marvasti, Laleh

    2014-01-01

    Introduction: Teeth with irreversible pulpitis usually undergo root canal therapy (RCT). This treatment modality is often considered disadvantageous as it removes vital pulp tissue and weakens the tooth structure. A relatively new concept has risen which suggests vital pulp therapy (VPT) for irreversible pulpitis. VPT with calcium enriched mixture (VPT/CEM) has demonstrated favorable treatment outcomes when treating permanent molars with irreversible pulpitis. This study aims to compare patient related factors, safety and organizational consideration as parts of health technology assessment (HTA) of the new VPT/CEM biotechnology when compared with RCT. Materials and Methods: Patient related factors were assessed by looking at short- and long-term clinical success; safety related factors were evaluated by a specialist committee and discussion board involved in formulating healthcare policies. Organizational evaluation was performed and the social implications were assessed by estimating the costs, availability, accessibility and acceptability. The impact of VPT/CEM biotechnology was assessed by investigating the incidence of irreversible pulpitis and the effect of this treatment on reducing the burden of disease. Results: VPT/CEM biotechnology was deemed feasible and acceptable like RCT; however, it was more successful, accessible, affordable, available and also safer than RCT. Conclusion: When considering socioeconomic implications on oral health status and oral health-related quality of life of VPT/CEM, the novel biotechnology can be more effective and more efficient than RCT in mature permanent molars with irreversible pulpitis. PMID:24396372

  19. Irreversibility line in superconductor as line of constant shielding current density

    SciTech Connect

    Goemoery, F.; Takacs, S.; Holubar, T.

    1997-06-01

    The irreversibility of magnetic properties of superconductors is due to the existence of macroscopic shielding currents persisting for some period of time. The same currents offer nearly lossless electricity transport. Thus, the extent of magnetic irreversibility is directly proportional to the current-carrying capacity of a superconductor. Because the current-carrying capacity is an intrinsic property of the material, various experimental techniques should give the same irreversibility line corresponding to the same macroscopic shielding current density. Following this approach, the authors compared the irreversibility lines obtained from AC susceptibility measurement with those determined from quasistatic magnetization loops recorded with the help of a SQUID susceptometer. An additional parameter which has to be comparable is the electrical field characterizing the rate of change of the magnetic field. Fulfilling these conditions of equivalency, the authors found that it is possible to explain the irreversibility lines obtained by various techniques and at different conditions by the same physical model. They demonstrate that for the data, taken within two orders of magnitude for the current density and more than seven orders of magnitude for the electrical field, a consistent picture expressing all the observed features by the same model can be found. Measurements are presented from YBCO samples.

  20. Optimization of the performance characteristics in an irreversible magnetic Ericsson refrigeration cycle

    NASA Astrophysics Data System (ADS)

    Xia, Z. R.; Ye, X. M.; Lin, G. X.; Brück, E.

    2006-05-01

    A general model of an irreversible Ericsson refrigeration cycle employing paramagnetic materials as the working substance is presented, in which multi-irreversibilities such as finite-rate heat transfer, regenerative loss, heat leak, efficiency of regenerator and internal irreversibility resulting from magnetic working substances are taken into account. On the basis of the general thermodynamic properties of paramagnetic materials and the optimal-control theory, the optimal mathematical expressions of cooling load, coefficient of performance and power input of the irreversible Ericsson refrigeration cycle using paramagnetic materials as the working substance are derived. By means of a numerical approach, the influence of the heat leak, the internal irreversibility, the efficiency of regenerator, the ratio of the magnetic fields on the cyclic performance characteristics of the refrigeration cycle are revealed and discussed in detail. Some important performance bounds, e.g. the maximum cooling load and the corresponding coefficient of performance, the maximum coefficient of performance and the corresponding cooling load, are determined and evaluated. Furthermore, several special cases may be deduced from the primary results in this paper. The conclusions obtained in the present paper are more general and useful than those existing in literature and can provide some new important information for the optimal design and performance improvement of magnetic refrigerators.

  1. The optimal operating temperature of the collector of an irreversible solar-driven refrigerator

    NASA Astrophysics Data System (ADS)

    Lin, Guoxing; Yan, Zijun

    1999-01-01

    A universal irreversible solar-driven refrigerator model is presented, in which not only the irreversibility of heat conduction but also the irreversibilities resulting from the friction, eddies and other irreversible effects inside the working fluid are considered. On the basis of this model and the linear heat-loss model of a solar collector, one of the important parameters, called the optimal operating temperature of the collector of a solar-driven refrigerator, is derived by using the finite-time thermodynamic theory. From the result, the maximum overall coefficient of performance of the refrigerator is determined and some significant problems are discussed. The results obtained here are quite realistic and universal, insofar as all the corresponding results derived by using the reversible and endoreversible models and the model considering only the internal irreversibility cycle can be deduced from them. Thus, they may provide some new theoretical bases for further exploitation of solar-driven refrigerators. Furthermore, some shortcoming in the related literature are pointed out.

  2. Reversible and irreversible emission of methanethiol and dimethyl disulfide from anaerobically stored broccoli.

    PubMed

    Tulio, Artemio Z; Yamanaka, Hiroyuki; Ueda, Yoshinori; Imahori, Yoshihiro; Chachin, Kazuo

    2003-11-05

    The reversible and irreversible emission of methanethiol (MT) and dimethyl disulfide (DMDS) from broccoli florets was demonstrated during anaerobic storage at 20 degrees C for up to 24 h. Reversible emission of MT and DMDS was feasible only in broccoli stored for between 0 and 12 h under entirely anaerobic condition. Beyond that, the emission was completely irreversible. This irreversible process was demonstrated through significant reductions in the chlorophyll fluorescence values and rate of carbon dioxide production and significant increase in the membrane permeability of induced broccoli tissues after exposure to air and incubation. Irreversible emission was also demonstrated through significant change in color from the characteristic bright green to olive green as well as the conversion of chlorophyll a to pheophytin a and chlorophyll a' contents of the induced florets after hot-water treatment. These findings suggest that the irreversible emission of MT and DMDS is a function of permanent membrane damage and loss of intracellular compartmentation in the broccoli tissues as a result of the anaerobic induction. The off-odor formation can still be reversed if the affected tissue is only temporarily impaired by anaerobic condition, thereby maintaining the quality of stored broccoli.

  3. Inactivation of Escherichia coli phage by pulsed electric field treatment and analysis of inactivation mechanism

    NASA Astrophysics Data System (ADS)

    Tanino, Takanori; Yoshida, Tomoki; Sakai, Kazuki; Ohshima, Takayuki

    2013-03-01

    Inactivation of bacteriophage by pulsed electric field (PEF) treatment, one of the effective procedures for bacteria nonthermal inactivation, was studied. Model phage particles Escherichia coli bacteriophages M13mp18 and λ phage, were successfully inactivated by PEF treatment. The survival ratios of both bacteriophages decreased depending on the PEF treatment time when applied peak voltage was 5 or 7 kV, and the survival ratios after 12 min PEF treatment were 10-4 - 10-5. Electrophoresis analyses of biological molecules of inactivated λ phage detected no degradation of total protein and genomic DNA. These results suggested that the factor of phage inactivation by PEF treatment was not based on the degradation of protein or DNA, but on the destruction of phage particle structure. Sensitivity of E. coli phage to PEF treatment was compared with that of E. coli cell. Phage and MV1184 cell were treated with same condition PEF at 5 kV, respectively. After 12 min treatment, the survival ration of λ phage and MV1184 were 4.0 × 10-5 and 1.7 × 10-3, respectively. The survival ratio of phage was lower than that of MV1184. E. coli cell is more tolerant to inactivation with PEF treatment than coli phage.

  4. Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.

    PubMed

    Boucherat, Olivier; Landry-Truchon, Kim; Bérubé-Simard, Félix-Antoine; Houde, Nicolas; Beuret, Laurent; Lezmi, Guillaume; Foulkes, William D; Delacourt, Christophe; Charron, Jean; Jeannotte, Lucie

    2015-09-01

    Yin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation whereas Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching and caused airway dilation similar to that seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be partly explained by the reduced expression of Shh, a transcriptional target of YY1, in lung endoderm, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the crucial requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB.

  5. Is hydrogen peroxide involved in the benzyl viologen-mediated in-vivo inactivation of rat liver glutamine synthetase?

    PubMed Central

    Muriana, F. J.; Ruiz-Gutierrez, V.; Relimpio, A. M.

    1993-01-01

    After benzyl viologen administration to rats, a decrease in the rat liver glutamine synthetase activity was observed. An increase in the rat liver catalase activity was found concomitantly. In combination with the catalase inhibitor aminotriazole, benzyl viologen again diminished, but markedly, the rat liver glutamine synthetase activity. Moreover, partially purified glutamine synthetase from rat liver underwent rapid inactivation upon aerobic incubation with NAD(P)H and benzyl viologen. This inactivation was prevented by catalase, which suggests that the NAD(P)H/BV2+/O2-dependent system has a role in H2O2 production. Our results suggest that H2O2 is involved in the benzyl viologen-mediated in-vivo inactivation of the rat liver glutamine synthetase. In contrast, benzyl viologen alone or in combination with aminotriazole produced a significant increase of brain glutamine synthetase. PMID:8098954

  6. Effects of Bacterial Inactivation Methods on Downstream Proteomic Analysis

    SciTech Connect

    Lin, Andy; Merkley, Eric D.; Clowers, Brian H.; Hutchison, Janine R.; Kreuzer, Helen W.

    2015-05-01

    Inactivation of pathogenic microbial samples is often necessary for the protection of researchers and to comply with local and federal regulations. By its nature, biological inactivation causes changes to microbial samples, potentially affecting observed experimental results. While inactivation induced damage to materials such as DNA has been evaluated, the effect of various inactivation strategies on proteomic data, to our knowledge, has not been discussed. To this end, we inactivated samples of Yersinia pestis and Escherichia coli by autoclave, ethanol, or irradiation treatment to determine how inactivation changes liquid chromatography tandem mass spectrometry data quality as well as apparent protein content of cells. Proteomic datasets obtained from aliquots of samples inactivated by different methods were highly similar, with Pearson correlation coefficients ranging from 0.822 to 0.985 and 0.816 to 0.985 for E. coli and Y. pestis, respectively, suggesting that inactivation had only slight impacts on the set of proteins identified. In addition, spectral quality metrics such as distributions of various database search algorithm scores remained constant across inactivation methods, indicating that inactivation does not appreciably degrade spectral quality. Though overall changes resulting from inactivation were small, there were detectable trends. For example, one-sided Fischer exact tests determined that periplasmic proteins decrease in observed abundance after sample inactivation by autoclaving (α = 1.71x10-2 for E. coli, α = 4.97x10-4 for Y. pestis) and irradiation (α = 9.43x10-7 for E. coli, α = 1.21x10-5 for Y. pestis) when compared to controls that were not inactivated. Based on our data, if sample inactivation is necessary, we recommend inactivation with ethanol treatment with secondary preference given to irradiation.

  7. Effects of bacterial inactivation methods on downstream proteomic analysis.

    PubMed

    Lin, Andy; Merkley, Eric D; Clowers, Brian H; Hutchison, Janine R; Kreuzer, Helen W

    2015-05-01

    Inactivation of pathogenic microbial samples is often necessary for the protection of researchers and to comply with local and federal regulations. By its nature, biological inactivation causes changes to microbial samples, potentially affecting observed experimental results. While inactivation-induced damage to materials such as DNA has been evaluated, the effect of various inactivation strategies on proteomic data, to our knowledge, has not been discussed. To this end, we inactivated samples of Yersinia pestis and Escherichia coli by autoclave, ethanol, or irradiation treatment to determine how inactivation changes liquid chromatography-tandem mass spectrometry data quality as well as apparent protein content of cells. Proteomic datasets obtained from aliquots of samples inactivated by different methods were highly similar, with Pearson correlation coefficients ranging from 0.822 to 0.985 and 0.816 to 0.985 for E. coli and Y. pestis, respectively, suggesting that inactivation had only slight impacts on the set of proteins identified. In addition, spectral quality metrics such as distributions of various database search algorithm scores remained constant across inactivation methods, indicating that inactivation does not appreciably degrade spectral quality. Though overall changes resulting from inactivation were small, there were detectable trends. For example, one-sided Fischer exact tests determined that periplasmic proteins decrease in observed abundance after sample inactivation by autoclaving (α=1.71×10(-2) for E. coli, α=4.97×10(-4) for Y. pestis) and irradiation (α=9.43×10(-7) for E. coli, α=1.21×10(-5) for Y. pestis) when compared to controls that were not inactivated. Based on our data, if sample inactivation is necessary, we recommend inactivation with ethanol treatment with secondary preference given to irradiation.

  8. Performance analysis and parametric optimum criteria of an irreversible Bose-Otto engine

    NASA Astrophysics Data System (ADS)

    Wang, Hao; Liu, Sanqiu; He, Jizhou

    2009-04-01

    An irreversible cycle model of a Bose-Otto engine is established, in which finite time thermodynamic processes and the irreversibility result from the nonisentropic compression and expansion processes are taken into account. Based on the model, expressions for the power output and efficiency of the Bose-Otto engine are derived. On the basis of the thermodynamic properties of ideal Bose gas, the effects of the irreversibility and the compression ratio of the two isochoric processes on the performance of the Bose-Otto engine are revealed and some important performance parameters are optimized. Furthermore, some optimal operating regions including those for the power output, efficiency, and the temperatures of the cyclic working substance at two important state points are determined and evaluated. Finally, several special cases are discussed in detail.

  9. Optimization of the performance characteristics in an irreversible regeneration magnetic Brayton refrigeration cycle

    NASA Astrophysics Data System (ADS)

    Wang, Hao; Wu, GuoXing

    2012-02-01

    A model of the irreversible regenerative Brayton refrigeration cycle working with paramagnetic materials is established, in which the regeneration problem in two constant-magnetic field processes and the irreversibility in two adiabatic processes are considered synthetically. Expressions for the COP, cooling rate, power input, the minimum ratio of the two magnetic fields, etc., are derived. It is found that the influence of the irreversibility and the regeneration on the main performance parameters of the magnetic Brayton refrigerator is remarkable. It is important that we have obtained several optimal criteria, which may provide some theoretical basis for the optimal design and operation of the Brayton refrigerator. The results obtained in the paper can provide some new theoretical information for the optimal design and performance improvement of real Brayton refrigerators.

  10. Classifying of financial time series based on multiscale entropy and multiscale time irreversibility

    NASA Astrophysics Data System (ADS)

    Xia, Jianan; Shang, Pengjian; Wang, Jing; Shi, Wenbin

    2014-04-01

    Time irreversibility is a fundamental property of many time series. We apply the multiscale entropy (MSE) and multiscale time irreversibility (MSTI) to analyze the financial time series, and succeed to classify the financial markets. Interestingly, both methods have nearly the same classification results, which mean that they are capable of distinguishing different series in a reliable manner. By comparing the results of shuffled data with the original results, we confirm that the asymmetry property is an inherent property of financial time series and it can extend over a wide range of scales. In addition, the effect of noise on Americas markets and Europe markets are relatively more significant than the effect on Asia markets, and loss of time irreversibility has been detected in high noise added series.

  11. Cloning of a nitrate reductase inactivator (NRI) cDNA from Spinacia oleracea L. and expression of mRNA and protein of NRI in cultured spinach cells.

    PubMed

    Sonoda, Masatoshi; Ide, Hiroaki; Nakayama, Shinya; Sasaki, Asako; Kitazaki, Shinei; Sato, Takahide; Nakagawa, Hiroki

    2003-04-01

    The spinach ( Spinacia oleracea L. (cv. Hoyo) nitrate reductase inactivator (NRI) is a novel protein that irreversibly inactivates NR. Using degenerate primers based on an N-terminal amino acid sequence of NRI purified from spinach leaves and a cDNA library, we isolated a full-length NRI cDNA from spinach that contains an open reading frame encoding 479 amino acid residues. This protein shares 67.4% and 51.1-68.3% amino acid sequence similarities with a nucleotide pyrophosphatase (EC 3.6.1.9) from rice and three types of the nucleotide pyrophosphatase-like protein from Arabidopsis thaliana, respectively. Immunoblot analysis revealed that NRI was constitutively expressed in suspension-cultured spinach cells; however, its expression level is quite low in 1-day-subcultured cells. Moreover, northern blot analysis indicated that this expression was regulated at the mRNA level. These results suggest that NRI functions in mature cells.

  12. Use of laser-UV for inactivation of virus in blood products

    SciTech Connect

    Prodouz, K.N.; Fratantoni, J.C.; Boone, E.J.; Bonner, R.F.

    1987-08-01

    Inactivation of virus by UV radiation was examined as a potential method for sterilization of blood products. Samples of attenuated poliovirus, platelets and plasma were uniformly irradiated with a XeCl excimer laser that delivered 40 nsec pulses of UV at 308 nm (UVB308). Intensities and exposure does were varied from 0.11 to 1.40 MW/cm2 and 0.51 to 56.0 J/cm2, respectively. In studies conducted with low intensity UVB308 (less than or equal to 0.17 MW/cm2), using exposure doses greater than or equal to 10.8 J/cm2, it was possible to inactivate poliovirus by 4 to 6 log10. Platelets irradiated with doses less than or equal to 21.5 J/cm2 exhibited minimal damage as assessed by aggregation activity and spontaneous release of serotonin. Examination of the coagulation activity of irradiated plasma indicated that exposure doses less than or equal to 21.5 J/cm2 resulted in less than 20% increase in prothrombin and partial thromboplastin times. The use of UVB308 at a higher intensity (1.4 MW/cm2) over a similar range of exposure doses did not enhance viral inactivation but did result in increased damage to platelet and plasma proteins. These results demonstrate that at 308 nm there exists a window of efficacy for exposure doses between 10.8 and 21.5 J/cm2 and peak intensities less than or equal to 0.17 MW/cm2 in which a hardy virus is significantly inactivated and platelets and plasma proteins are, by functional criteria, minimally affected. Increased viral inactivation cannot be accomplished with higher UV intensities and will require additional or alternate measures.

  13. Enhanced irreversible sorption of carbaryl to soils amended with crop-residue-derived biochar.

    PubMed

    Qiu, Yuping; Wu, Minwei; Jiang, Jing; Li, Liang; Sheng, G Daniel

    2013-09-01

    The irreversible sorption-desorption of carbaryl in five soil types with crop-residue-derived biochar (CBC) amendment was determined. CBC has lower surface area and micropores volume than wood-based biochar and charcoal. However, CBC amendment (0.5%) still significantly enhanced the hysteresis effect on soils, with a 1.7- to 2.8-fold increase in the hysteresis index (HI) values. The HI values increased exponentially with the increased amount of CBC but decreased exponentially with the increased amount of soil organic matter (SOM%). Furthermore, the irreversible carbaryl sorption (qirr) and the irreversibility index (Iirr) values were proportional to the amount of CBC (0-1.0%) in soils. Likewise, the SOM-rich soil (S3) was washed ten times to reduce its SOM% to evaluate the influence of the dissolved organic matter (DOM) in the soils on the irreversible sorption. The Iirr values of the unamended S3 increased as the number of sorption-desorption cycles increased, whereas those of the 1.0% CBC-amended S3 decreased. In addition, the Iirr values of the unwashed S3 were lower than those of the washed S3. By contrast, the Iirr values of the 1.0% CBC-amended S3 soil were higher in the unwashed samples than in the washed samples. These results suggested that DOM had opposite effects on the irreversible carbaryl sorption by unamended and CBC-amended soils. The DOM release may expose more irreversible adsorption sites in the soils and may cover the surface of the CBC to form a desorption-resistant fraction in its mesopore or macropore regions, thereby preventing the desorption of adsorbed carbaryl molecules.

  14. Partial Torus Instability

    NASA Astrophysics Data System (ADS)

    Olmedo, Oscar; Zhang, J.

    2010-05-01

    Flux ropes are now generally accepted to be the magnetic configuration of Coronal Mass Ejections (CMEs), which may be formed prior or during solar eruptions. In this study, we model the flux rope as a current-carrying partial torus loop with its two footpoints anchored in the photosphere, and investigate its instability in the context of the torus instability (TI). Previous studies on TI have focused on the configuration of a circular torus and revealed the existence of a critical decay index. Our study reveals that the critical index is a function of the fractional number of the partial torus, defined by the ratio between the arc length of the partial torus above the photosphere and the circumference of a circular torus of equal radius. We refer to this finding the partial torus instability (PTI). It is found that a partial torus with a smaller fractional number has a smaller critical index, thus requiring a more gradually decreasing magnetic field to stabilize the flux rope. On the other hand, the partial torus with a larger fractional number has a larger critical index. In the limit of a circular torus when the fractional number approaches one, the critical index goes to a maximum value that depends on the distribution of the external magnetic field. We demonstrate that the partial torus instability helps us to understand the confinement, growth, and eventual eruption of a flux rope CME.

  15. Irreversible Horner’s syndrome diagnosed by aproclonidine test due to benign thyroid nodule

    PubMed Central

    M, Coskun; A, Aydogan; C, Gokce; O, Ilhan; OV, Ozkan; H, Gokce; H, Oksuz

    2013-01-01

    We are reporting an irreversible Horner Syndrome (HS) in a patient with benign thyroid gland nodule in which thyroidectomy was performed for treatment. A 37-year-old female was admitted to our clinic with a swelling in the left lobe of the thyroid gland and ptosis at the left eyelid. The clinical diagnosis of HS was confirmed pharmacologically by aproclonidine. Histopathologic examination of thyroidectomy specimen was reported as benign nodule. To the best of our knowledge, this is a very rare report in terms of thyroid benign nodule associated with irreversible HS due to cervical sympathetic chain compression. PMID:24353546

  16. Irreversible event-based model for thermal emission of electrons from isolated traps

    NASA Astrophysics Data System (ADS)

    Dimitrijev, Sima

    2009-05-01

    In spite of the irreversible nature of macroscopic processes, our understanding of the fundamental physical phenomena remains limited to reversible models (the Loschmidt's paradox). We propose a direct irreversible model for the probability per unit time that an electron will be emitted from an isolated trap. This resolves a number of problems, including (1) the dubious link between emission measurements and the parameters of the independent capture process and (2) the elusive meaning of the degeneracy factor in the equilibrium Fermi-Dirac distribution.

  17. An Irreversible Constitutive Law for Modeling the Delamination Process Using Interface Elements

    NASA Technical Reports Server (NTRS)

    Goyal, Vinay K.; Johnson, Eric R.; Davila, Carlos G.; Jaunky, Navin; Bushnell, Dennis M. (Technical Monitor)

    2002-01-01

    An irreversible constitutive law is postulated for the formulation of interface elements to predict initiation and progression of delamination in composite structures. An exponential function is used for the constitutive law such that it satisfies a multi-axial stress criterion for the onset of delamination, and satisfies a mixed mode fracture criterion for the progression of delamination. A damage parameter is included to prevent the restoration of the previous cohesive state between the interfacial surfaces. To demonstrate the irreversibility capability of the constitutive law, steady-state crack growth is simulated for quasi-static loading-unloading cycle of various fracture test specimens.

  18. An Irreversible Constitutive Law for Modeling the Delamination Process using Interface Elements

    NASA Technical Reports Server (NTRS)

    Goyal, Vinay K.; Johnson, Eric R.; Davila, Carlos G.; Jaunky, Navin; Ambur, Damodar (Technical Monitor)

    2002-01-01

    An irreversible constitutive law is postulated for the formulation of interface elements to predict initiation and progression of delamination in composite structures. An exponential function is used for the constitutive law such that it satisfies a multi-axial stress criterion for the onset of delamination, and satisfies a mixed mode fracture criterion for the progression of delamination. A damage parameter is included to prevent the restoration of the previous cohesive state between the interfacial surfaces. To demonstrate the irreversibility capability of the constitutive law, steady-state crack growth is simulated for quasi-static loading-unloading cycle of various fracture test specimens.

  19. Quasi-specific access of the potassium channel inactivation gate.

    PubMed

    Venkataraman, Gaurav; Srikumar, Deepa; Holmgren, Miguel

    2014-06-09

    Many voltage-gated potassium channels open in response to membrane depolarization and then inactivate within milliseconds. Neurons use these channels to tune their excitability. In Shaker K(+) channels, inactivation is caused by the cytoplasmic amino terminus, termed the inactivation gate. Despite having four such gates, inactivation is caused by the movement of a single gate into a position that occludes ion permeation. The pathway that this single inactivation gate takes into its inactivating position remains unknown. Here we show that a single gate threads through the intracellular entryway of its own subunit, but the tip of the gate has sufficient freedom to interact with all four subunits deep in the pore, and does so with equal probability. This pathway demonstrates that flexibility afforded by the inactivation peptide segment at the tip of the N-terminus is used to mediate function.

  20. Mechanism-based inactivation of lacrimal-gland peroxidase by phenylhydrazine: a suicidal substrate to probe the active site.

    PubMed Central

    Mazumdar, A; Adak, S; Chatterjee, R; Banerjee, R K

    1997-01-01

    Humans are exposed to various hydrazine derivatives for therapeutic control of several diseases, and mammalian peroxidases are implicated in the oxidative metabolism of many drugs. The results presented here indicate that lacrimal-gland peroxidase is irreversibly inactivated in a mechanism-based way by phenylhydrazine, which acts as a suicidal substrate in the presence of H2O2. The pseudo-first-order kinetic constants for inactivation at pH 5.5 are Ki=18 microM, kinact=0.25 min-1 and tau50=2.75 min, with a second-order rate constant of 0.75x10(4) M-1.min-1. Approx. 27 mol of phenylhydrazine and 54 mol of H2O2 are required per mol of enzyme for complete inactivation. The pH-dependent inactivation kinetics indicate the involvement of an ionizable group on the enzyme with a pKa value of 5.4, protonation of which favours inactivation. SCN-, the plausible physiological electron donor of the enzyme, protects it from inactivation. Binding studies by optical difference spectroscopy indicate that phenylhydrazine interacts with the enzyme with a KD value of 60 microM, and its binding is prevented by the presence of SCN-. The enzyme is also protected by 5, 5-dimethyl-1-pyrroline N-oxide, a free-radical trap, suggesting the involvement of a radical species in the inactivation. ESR studies indicate the formation of a spin-trapped phenyl radical (aN=15.9G and abetaH=24.8G) generated on incubation of phenylhydrazine with the enzyme and H2O2. A 75% loss of the Soret spectrum is observed when the enzyme is completely inactivated. However, in the presence of the spin trap, spectral loss is prevented and the enzyme compound II is readily reduced to the native state by phenylhydrazine. The phenylhydrazine-inactivated enzyme reacts with H2O2 or CN- to form compound II or the cyanide complex with a characteristic spectrum, indicating that haem iron is protected from attack by the radical species. The inactivated enzyme binds SCN- with a KD value similar to that of the native enzyme (15

  1. Antibacterial efficacy and effect of chlorhexidine mixed with irreversible hydrocolloid for dental impressions: a randomized controlled trial.

    PubMed

    Cubas, Glória; Valentini, Fernanda; Camacho, Guilherme Brião; Leite, Fábio; Cenci, Maximiliano Sérgio; Pereira-Cenci, Tatiana

    2014-01-01

    This study aimed to evaluate whether chlorhexidine mixed with irreversible hydrocolloid powder decreases microbial contamination during impression taking without affecting the resulting casts. Twenty volunteers were randomly divided into two groups (n = 10) according to the liquid used for impression taking in conjunction with irreversible hydrocolloid: 0.12% chlorhexidine or water. Surface roughness and dimensional stability of the casts were evaluated. Chlorhexidine mixed with irreversible hydrocolloid decreased the percentage of microorganisms when compared with water (P < .001) but did not affect the surface quality or dimensional stability of the casts. Mixing chlorhexidine with irreversible hydrocolloid powder is an alternative method to prevent contamination without sacrificing impression quality.

  2. Thermal inactivation of bovine immunodeficiency virus.

    PubMed Central

    Moore, E C; Keil, D; Coats, K S

    1996-01-01

    Cell-associated bovine immunodeficiency virus (BIV) and cell-free BIV were subjected to increasing temperatures, including pasteurization conditions. To determine the effect of heat treatment on BIV viability, reverse transcriptase activity and infectivity of the heat-treated virus were assessed. BIV was inactivated by heating to 47 degrees C for 30 min and by low- and high-temperature pasteurization conditions. PMID:8900024

  3. Pathogen Inactivated Plasma Concentrated: Preparation and Uses

    DTIC Science & Technology

    2004-09-01

    http://www.navigantbiotech.com, 2004 [5] Wagner SJ, “Virus inactivation in blood components by photoactive phenothiazine dyes,” Transfus Med Rev...their fellow soldiers is a time- honored military tradition, it is inherently limited. The only remaining option is therefore to collect blood ... components from the indigenous populations, but this approach carries a great risk of dangerous infections, particularly in third world countries. For an

  4. Female meiotic sex chromosome inactivation in chicken.

    PubMed

    Schoenmakers, Sam; Wassenaar, Evelyne; Hoogerbrugge, Jos W; Laven, Joop S E; Grootegoed, J Anton; Baarends, Willy M

    2009-05-01

    During meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI) leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (ZW), whereas males have the homogametic ZZ constitution. During chicken oogenesis, the heterologous ZW pair reaches a state of complete heterologous synapsis, and this might enable maintenance of transcription of Z- and W chromosomal genes during meiotic prophase. Herein, we show that the ZW pair is transiently silenced, from early pachytene to early diplotene using immunocytochemistry and gene expression analyses. We propose that ZW inactivation is most likely achieved via spreading of heterochromatin from the W on the Z chromosome. Also, persistent meiotic DNA double-strand breaks (DSBs) may contribute to silencing of Z. Surprisingly, gammaH2AX, a marker of DSBs, and also the earliest histone modification that is associated with XY body formation in mammalian and marsupial spermatocytes, does not cover the ZW during the synapsed stage. However, when the ZW pair starts to desynapse, a second wave of gammaH2AX accumulates on the unsynapsed regions of Z, which also show a reappearance of the DSB repair protein RAD51. This indicates that repair of meiotic DSBs on the heterologous part of Z is postponed until late pachytene/diplotene, possibly to avoid recombination with regions on the heterologously synapsed W chromosome. Two days after entering diplotene, the Z looses gammaH2AX and shows reactivation. This is the first report of meiotic sex chromosome inactivation in a species with female heterogamety, providing evidence that this mechanism is not specific to spermatogenesis. It also indicates the presence of an evolutionary force that drives meiotic sex chromosome inactivation independent of the final achievement of synapsis.

  5. Thymineless Death in Escherichia coli: Inactivation and Recovery

    PubMed Central

    Cummings, Donald J.; Kusy, Alvin R.

    1969-01-01

    The effects of chloramphenicol (CAP) on the progress of thymineless death (TLD), nalidixic acid (NA) inactivation, ultraviolet (UV) irradiation, and mitomycin C (MC) inactivation were studied in Escherichia coli B, Bs−1, Bs−3, Bs−12, and B/r. This was done before, during, and after inactivation. During the progress of inactivation, it was found that at 10 to 20 μg of CAP per ml, up to 50% of the UV-sensitive bacteria survived TLD and about 10% survived NA. In E. coli B/r, at these concentrations of CAP, about 10 to 15% of the cells survived TLD and about 20 to 25% survived NA. Concentrations of CAP greater than 25 μg/ml actually increased the sensitivity of E. coli B, Bs−1, Bs−3, and Bs−12 to inactivation by either TLD or NA; at 150 μg of CAP per ml, the sensitivity of E. coli B/r to inactivation also increased. When E. coli B cells were incubated in CAP prior to inactivation, the longer the preincubation the longer onset of TLD was delayed; NA inactivation was also affected in that the rate of inactivation after CAP incubation was greatly decreased. Preincubation of E. coli B/r with CAP had much less effect on the progress of inactivation. After thymineless death, incubation in CAP plus thymine led to a rapid and almost complete recovery of E. coli B and Bs−12. Lesser recoveries were observed after inactivation due to UV, NA, or MC inactivation. E. coli Bs−1 and B/r did not recover viability after any mode of inactivation, and E. coli Bs−3 and Bs−12 recovered from UV to about 20% of the initial titer. It was suggested that protein synthesis, in particular proteins involved in deoxyribonucleic synthesis, was a determining factor in these inactivating and recovery events. PMID:4897115

  6. Partial knee replacement - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100225.htm Partial knee replacement - series—Normal anatomy To use the sharing ... A.M. Editorial team. Related MedlinePlus Health Topics Knee Replacement A.D.A.M., Inc. is accredited ...

  7. Twisted partially pure spinors

    NASA Astrophysics Data System (ADS)

    Herrera, Rafael; Tellez, Ivan

    2016-08-01

    Motivated by the relationship between orthogonal complex structures and pure spinors, we define twisted partially pure spinors in order to characterize spinorially subspaces of Euclidean space endowed with a complex structure.

  8. Developmental regulation of X-chromosome inactivation.

    PubMed

    Payer, Bernhard

    2016-08-01

    With the emergence of sex-determination by sex chromosomes, which differ in composition and number between males and females, appeared the need to equalize X-chromosomal gene dosage between the sexes. Mammals have devised the strategy of X-chromosome inactivation (XCI), in which one of the two X-chromosomes is rendered transcriptionally silent in females. In the mouse, the best-studied model organism with respect to XCI, this inactivation process occurs in different forms, imprinted and random, interspersed by periods of X-chromosome reactivation (XCR), which is needed to switch between the different modes of XCI. In this review, I describe the recent advances with respect to the developmental control of XCI and XCR and in particular their link to differentiation and pluripotency. Furthermore, I review the mechanisms, which influence the timing and choice, with which one of the two X-chromosomes is chosen for inactivation during random XCI. This has an impact on how females are mosaics with regard to which X-chromosome is active in different cells, which has implications on the severity of diseases caused by X-linked mutations.

  9. Rapid inactivation of SARS-like coronaviruses.

    SciTech Connect

    Kapil, Sanjay; Oberst, R. D.; Bieker, Jill Marie; Tucker, Mark David; Souza, Caroline Ann; Williams, Cecelia Victoria

    2004-03-01

    Chemical disinfection and inactivation of viruses is largely understudied, but is very important especially in the case of highly infectious viruses. The purpose of this LDRD was to determine the efficacy of the Sandia National Laboratories developed decontamination formulations against Bovine Coronavirus (BCV) as a surrogate for the coronavirus that causes Severe Acute Respiratory Syndrome (SARS) in humans. The outbreak of SARS in late 2002 resulted from a highly infectious virus that was able to survive and remain infectious for extended periods. For this study, preliminary testing with Escherichia coli MS-2 (MS-2) and Escherichia coli T4 (T4) bacteriophages was conducted to develop virucidal methodology for verifying the inactivation after treatment with the test formulations following AOAC germicidal methodologies. After the determination of various experimental parameters (i.e. exposure, concentration) of the formulations, final testing was conducted on BCV. All experiments were conducted with various organic challenges (horse serum, bovine feces, compost) for results that more accurately represent field use condition. The MS-2 and T4 were slightly more resistant than BCV and required a 2 minute exposure while BCV was completely inactivated after a 1 minute exposure. These results were also consistent for the testing conducted in the presence of the various organic challenges indicating that the test formulations are highly effective for real world application.

  10. Inactivation of Renibacterium salmoninarum by free chlorine

    USGS Publications Warehouse

    Pascho, Ronald J.; Landolt, Marsha L.; Ongerth, Jerry E.

    1995-01-01

    Salmonid fishes contract bacterial kidney disease by vertical or horizontal transmission of the pathogenic bacterium, Renibacterium salmoninarum. Procedures to reduce vertical transmission are under evaluation, but methods are still needed to eliminate sources of waterborne R. salmoninarum. We examined the efficacy of chlorine to inactivate R. salmoninarum. The bacterium was exposed to various levels of chlorine at pH 6, 7, or 8, and at 7.5 °C or 15 °C. At pH 7 and 15 °C, 99% inactivation occurred within 18 s, even at free chlorine concentrations as low as 0.05 mg/l. Chlorine was most effective at neutral or acidic pH, and 15 °C. The inactivation curves for 7.5 °C and pH 7, or 15 °C and pH 8, deviated from first-order kinetics by exhibiting shoulders or a tailing-off effect, suggesting that chlorine and the bacterial cells were not the sole reactants. A plot of the concentration-time (Ct) products for free chlorine at pH 7 and 15 °C produced a line with a slope less than 1, indicating that the duration of exposure was more important than the concentration of free chlorine. These data indicate that R. salmoninarum is very sensitive to chlorine, and that this disinfectant may be appropriate for use in fish hatcheries rearing salmonids affected by bacterial kidney disease.

  11. Partially coherent nonparaxial beams.

    PubMed

    Duan, Kailiang; Lü, Baida

    2004-04-15

    The concept of a partially coherent nonparaxial beam is proposed. A closed-form expression for the propagation of nonparaxial Gaussian Schell model (GSM) beams in free space is derived and applied to study the propagation properties of nonparaxial GSM beams. It is shown that for partially coherent nonparaxial beams a new parameter f(sigma) has to be introduced, which together with the parameter f, determines the beam nonparaxiality.

  12. Rabies virus inactivation by binary ethylenimine: new method for inactivated vaccine production.

    PubMed Central

    Larghi, O P; Nebel, A E

    1980-01-01

    The inactivation dynamics of rabies virus (PV strain) by binary ethylenimine, and the immunogenic properites and the stability of the vaccines prepared using this agent, were studied. Binary ethylenimine at a final concentration of 0.01 M was prepared wtih 2-bromoethylamine hydrobromide in alkaline solutions, either separately from or in suspensions of rabies virus propagated in BHK cells. The infectivity of virus suspensions containing more than 108 plaque-forming units per 0.1 ml was inactivated in 2 h when the inactivating agent was prepared before its addition to the suspensions, and in3 h when prepared directly in the suspensions. Liquid vaccines prepared in this manner and stored at different temperatures maintained potency for 1 month at 37 degrees C and for 6 months at 4 degrees C and 22 to 25 degrees C. Lyophilized vaccine maintained its potency for 6 months at the three temperatures. The inactivated vaccine mixed with aluminum or oil adjuvant at high dilutions protected guinea pigs against challenge. This safer procedure for rabies virus inactivation offers promise for the production of effective vaccines for the immunization of dogs and cattle. PMID:7358836

  13. Sodium channel inactivation in the crayfish giant axon. Must channels open before inactivating

    SciTech Connect

    Bean, B.P.

    1981-09-01

    Experiments on sodium channel inactivation kinetics were performed on voltage-clamped crayfish giant axons. The primary goals was to investigate whether channels must open before activating. Voltage-clamp artifacts were minimized by the use of low-sodium solutions and full series resistance compensation, and the spatial uniformity of the currents was checked with a closely spaced pair of electrodes used to measure local current densities. For membrane potentials between -40 and +40 mV, sodium currents decay to zero with a single exponential time-course. The time constant for decay is a steep function of membrane potential. The time-course of inactivation measured with the double-pulse method is very similar to the decay of current at the same potential. Steady-state inactivation curves measured with different test pulses are identical. The time-course of doubling pulse inactivation shows a lag that roughly correlates with the opening of sodium channels, but it is not strictly necessary for channels to open before inactivating. Measurements of the potential dependence of the integral of sodium conductance are also inconsistent with the simplest cases of models in which channels must open before activating.

  14. MRI/DTI of the Brain Stem Reveals Reversible and Irreversible Disruption of the Baroreflex Neural Circuits: Clinical Implications.

    PubMed

    Su, Chia-Hao; Tsai, Ching-Yi; Chang, Alice Y W; Chan, Julie Y H; Chan, Samuel H H

    2016-01-01

    Baroreflex is the physiological mechanism for the maintenance of blood pressure and heart rate. Impairment of baroreflex is not a disease per se. However, depending on severity, the eventuality of baroreflex dysfunction varies from inconvenience in daily existence to curtailment of mobility to death. Despite universal acceptance, neuronal traffic within the contemporary neural circuits during the execution of baroreflex has never been visualized. By enhancing signal detection and fine-tuning the scanning parameters, we have successfully implemented tractographic analysis of the medulla oblongata in mice that allowed for visualization of connectivity between key brain stem nuclei in the baroreflex circuits. When viewed in conjunction with radiotelemetric analysis of the baroreflex, we found that under pathophysiological conditions when the disrupted connectivity between key nuclei in the baroreflex circuits was reversible, the associated disease condition (e.g. neurogenic hypertension) was amenable to remedial measures. Nevertheless, fatality ensues under pathological conditions (e.g. hepatic encephalopathy) when the connectivity between key substrates in the baroreflex circuits was irreversibly severed. MRI/DTI also prompted partial re-wiring of the contemporary circuit for baroreflex-mediated sympathetic vasomotor tone, and unearthed an explanation for the time lapse between brain death and the inevitable asystole signifying cardiac death that follows.

  15. Irreversible change of electric conduction in ionic-liquid-gated (La,Sr)MnO3 thin films

    NASA Astrophysics Data System (ADS)

    Lee, Tae Kwon; Jung, Jong Hoon

    2016-10-01

    We have investigated the ionic-liquid-gating effect on electric conduction in (La0.8Sr0.2)MnO3(LSMO) thin films. The gating effect is significant for the LSMO thin films grown at low oxygen partial pressures. We observed that the channel resistance of LSMO was altered only for a positive gating voltage, not for a negative one, mainly through the changes of mobility rather than the carrier density. The increased sheet resistance at positive voltage does not return to the original value even after the removal of gating voltage as well as the application of a negative voltage. Through the Mn 2 p X-ray absorption, the increased resistance of LSMO after a positive voltage is found to be associated with the increase of the Mn3+ ions over Mn4+ ones. We proposed that oxygen vacancy and electrochemical reactions should play a role for the irreversible electric conduction in ionic-liquid-gated (La,Sr)MnO3 thin films.

  16. Irreversible transformation of ferromagnetic ordered stripe domains in single-shot infrared-pump/resonant-x-ray-scattering-probe experiments

    NASA Astrophysics Data System (ADS)

    Bergeard, Nicolas; Schaffert, Stefan; López-Flores, Víctor; Jaouen, Nicolas; Geilhufe, Jan; Günther, Christian M.; Schneider, Michael; Graves, Catherine; Wang, Tianhan; Wu, Benny; Scherz, Andreas; Baumier, Cédric; Delaunay, Renaud; Fortuna, Franck; Tortarolo, Marina; Tudu, Bharati; Krupin, Oleg; Minitti, Michael P.; Robinson, Joe; Schlotter, William F.; Turner, Joshua J.; Lüning, Jan; Eisebitt, Stefan; Boeglin, Christine

    2015-02-01

    The evolution of a magnetic domain structure upon excitation by an intense, femtosecond infrared (IR) laser pulse has been investigated using single-shot based time-resolved resonant x-ray scattering at the x-ray free electron laser LCLS. A well-ordered stripe domain pattern as present in a thin CoPd alloy film has been used as a prototype magnetic domain structure for this study. The fluence of the IR laser pump pulse was sufficient to lead to an almost complete quenching of the magnetization within the ultrafast demagnetization process taking place within the first few hundreds of femtoseconds following the IR laser pump pulse excitation. On longer time scales this excitation gave rise to subsequent irreversible transformations of the magnetic domain structure. Under our specific experimental conditions, it took about 2 ns before the magnetization started to recover. After about 5 ns the previously ordered stripe domain structure had evolved into a disordered labyrinth domain structure. Surprisingly, we observe after about 7 ns the occurrence of a partially ordered stripe domain structure reoriented into a novel direction. It is this domain structure in which the sample's magnetization stabilizes as revealed by scattering patterns recorded long after the initial pump-probe cycle. Using micromagnetic simulations we can explain this observation based on changes of the magnetic anisotropy going along with heat dissipation in the film.

  17. PARTIAL TORUS INSTABILITY

    SciTech Connect

    Olmedo, Oscar; Zhang Jie

    2010-07-20

    Flux ropes are now generally accepted to be the magnetic configuration of coronal mass ejections (CMEs), which may be formed prior to or during solar eruptions. In this study, we model the flux rope as a current-carrying partial torus loop with its two footpoints anchored in the photosphere, and investigate its stability in the context of the torus instability (TI). Previous studies on TI have focused on the configuration of a circular torus and revealed the existence of a critical decay index of the overlying constraining magnetic field. Our study reveals that the critical index is a function of the fractional number of the partial torus, defined by the ratio between the arc length of the partial torus above the photosphere and the circumference of a circular torus of equal radius. We refer to this finding as the partial torus instability (PTI). It is found that a partial torus with a smaller fractional number has a smaller critical index, thus requiring a more gradually decreasing magnetic field to stabilize the flux rope. On the other hand, a partial torus with a larger fractional number has a larger critical index. In the limit of a circular torus when the fractional number approaches 1, the critical index goes to a maximum value. We demonstrate that the PTI helps us to understand the confinement, growth, and eventual eruption of a flux-rope CME.

  18. Partial Torus Instability

    NASA Astrophysics Data System (ADS)

    Olmedo, Oscar; Zhang, Jie

    2010-07-01

    Flux ropes are now generally accepted to be the magnetic configuration of coronal mass ejections (CMEs), which may be formed prior to or during solar eruptions. In this study, we model the flux rope as a current-carrying partial torus loop with its two footpoints anchored in the photosphere, and investigate its stability in the context of the torus instability (TI). Previous studies on TI have focused on the configuration of a circular torus and revealed the existence of a critical decay index of the overlying constraining magnetic field. Our study reveals that the critical index is a function of the fractional number of the partial torus, defined by the ratio between the arc length of the partial torus above the photosphere and the circumference of a circular torus of equal radius. We refer to this finding as the partial torus instability (PTI). It is found that a partial torus with a smaller fractional number has a smaller critical index, thus requiring a more gradually decreasing magnetic field to stabilize the flux rope. On the other hand, a partial torus with a larger fractional number has a larger critical index. In the limit of a circular torus when the fractional number approaches 1, the critical index goes to a maximum value. We demonstrate that the PTI helps us to understand the confinement, growth, and eventual eruption of a flux-rope CME.

  19. Structure of 6-Diazo-5-Oxo-Norleucine-Bound Human Gamma-Glutamyl Transpeptidase 1, a Novel Mechanism of Inactivation.

    PubMed

    Terzyan, Simon S; Cook, Paul F; Heroux, Annie; Hanigan, Marie H

    2017-04-05

    Intense efforts are underway to identify inhibitors of the enzyme gamma-glutamyl transpeptidase 1 (GGT1) which cleaves extracellular gamma-glutamyl compounds and contributes to the pathology of asthma, reperfusion injury and cancer. The glutamate analog, 6-diazo-5-oxo-norleucine (DON), inhibits GGT1. DON also inhibits many essential glutamine metabolizing enzymes rendering it too toxic for use in the clinic as a GGT1 inhibitor. We investigated the molecular mechanism of human GGT1 (hGGT1) inhibition by DON to determine possible strategies for increasing its specificity for hGGT1. DON is an irreversible inhibitor of hGGT1. The second order rate constant of inactivation was 0.052 mM(-1) min(-1) and the Ki was 2.7 ± 0.7 mM. The crystal structure of DON-inactivated hGGT1 contained a molecule of DON without the diazo-nitrogen atoms in the active site. The overall structure of the hGGT1-DON complex resembled the structure of the apo-enzyme; however, shifts were detected in the loop forming the oxyanion hole and elements of the main chain that form the entrance to the active site. The structure of hGGT1-DON complex revealed two covalent bonds between the enzyme and inhibitor which were part of a six membered ring. The ring included the OG atom of Thr381, the reactive nucleophile of hGGT1 and the α-amine of Thr381. The structure of DON-bound hGGT1 has led to the discovery of a new mechanism of inactivation by DON that differs from its inactivation of other glutamine metabolizing enzymes, and insight into the activation of the catalytic nucleophile that initiates the hGGT1 reaction. This article is protected by copyright. All rights reserved.

  20. Selective inactivation by 21-chlorinated steroids of rabbit liver and adrenal microsomal cytochromes P-450 involved in progesterone hydroxylation.

    PubMed

    Halpert, J; Jaw, J Y; Balfour, C; Mash, E A; Johnson, E F

    1988-08-01

    The inactivation by 21-chlorinated steroids of rabbit liver cytochromes P-450 involved in the hydroxylation of progesterone has been investigated in intact microsomes encompassing two phenotypes of 21-hydroxylase activity, two phenotypes of 16 alpha-hydroxylase activity, and three phenotypes of 6 beta-hydroxylase activity. In liver microsomes from outbred New Zealand White male rabbits exhibiting a high content of cytochrome P-450 1, 21,21-dichloropregnenolone caused a time- and NADPH-dependent loss of 21-hydroxylase activity. This loss of activity exhibited a number of characteristics of mechanism-based inactivation, including irreversibility, saturation with increasing inhibitor concentrations, and protection by substrate, and was also documented with purified P-450 1 in a reconstituted system. 21,21-Dichloropregnenolone caused no time-dependent loss of 6 beta-hydroxylase activity in microsomes from the New Zealand White rabbits or from control or rifampicin-treated rabbits of the inbred B/J strain. In contrast, in the microsomes from the B/J rabbits, some inactivation of the 16 alpha-hydroxylase was observed (k = 0.04 min-1), regardless of the rifampicin treatment. The other two compounds tested, 21-chloropregnenolone and 21,21-dichloroprogesterone, were less effective than the dichloropregnenolone as inactivators of cytochrome P-450 1. On the other hand, 21,21-dichloroprogesterone, but not 21,21-dichloropregneolone, caused a rapid time-dependent loss of 21-hydroxylase activity in rabbit adrenal microsomes. The results indicate that the introduction of a dichloromethyl group into a substrate bearing a methyl group normally hydroxylated by only one or a few forms of cytochrome P-450 may be a rational means of designing selective inhibitors of the enzyme.

  1. DOPAMINE RECEPTOR INACTIVATION IN THE CAUDATE-PUTAMEN DIFFERENTIALLY AFFECTS THE BEHAVIOR OF PREWEANLING AND ADULT RATS

    PubMed Central

    DER-GHAZARIAN, T.; GUTIERREZ, A.; VARELA, F. A.; HERBERT, M. S.; AMODEO, L. R.; CHARNTIKOV, S.; CRAWFORD, C. A.; MCDOUGALL, S. A.

    2012-01-01

    The irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) has been used to study the ontogeny of dopamine (DA) receptor functioning in the young and adult rat. Most notably, systemic administration of EEDQ blocks the DA agonist-induced behaviors of adult rats, while leaving the behavior of preweanling rats unaffected. The purpose of the present study was to: (a) determine whether the age-dependent actions of EEDQ involve receptors located in the dorsal caudate-putamen (CPu) and (b) confirm that EEDQ's behavioral effects result from the inactivation of DA receptors rather than some other receptor type. In Experiment 1, EEDQ or DMSO were bilaterally infused into the CPu on PD 17 or PD 84. After 24 h, rats were given bilateral microinjections of the full DA agonist R(–)-propylnorapomorphine (NPA) or vehicle into the dorsal CPu and behavior was assessed for 40 min. In Experiment 2, preweanling rats were treated as just described, except that DA receptors were protected from EEDQ-induced alkylation by administering systemic injections of D1 (SCH23390) and D2 (sulpiride) receptor antagonists. As predicted, microinjecting EEDQ into the dorsal CPu attenuated the NPA-induced locomotor activity and stereotypy of adult rats. In contrast, rats given bilateral EEDQ infusions on PD 17 exhibited a potentiated locomotor response when treated with NPA. Experiment 2 showed that DA receptor inactivation was responsible for NPA's actions. A likely explanation for these results is that EEDQ inactivates a sizable percentage of DA receptors on PD 17, but leaves the remaining receptors in a supersensitive state. This receptor supersensitivity, which probably involves alterations in G protein coupling, could account for NPA-induced locomotor potentiation. Either adult rats do not show a similar EEDQ-induced change in receptor dynamics or DA receptor inactivation was more complete in older animals and effectively eliminated the expression of DA agonist

  2. An inactivated influenza D virus vaccine partially protects cattle from respiratory disease caused by homologous challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Originally isolated from swine, the proposed influenza D virus has since been shown to be common in cattle. Inoculation of IDV to naïve calves resulted in mild respiratory disease histologically characterized by tracheitis. As several studies have associated the presence of IDV with acute bovine r...

  3. Selective rod degeneration and partial cone inactivation characterize an iodoacetic acid model of Swine retinal degeneration.

    PubMed

    Wang, Wei; Fernandez de Castro, Juan; Vukmanic, Eric; Zhou, Liang; Emery, Douglas; Demarco, Paul J; Kaplan, Henry J; Dean, Douglas C

    2011-10-07

    PURPOSE. Transgenic pigs carrying a mutant human rhodopsin transgene have been developed as a large animal model of retinitis pigmentosa (RP). This model displays some key features of human RP, but the time course of disease progression makes this model costly, time consuming, and difficult to study because of the size of the animals at end-stage disease. Here, the authors evaluate an iodoacetic acid (IAA) model of photoreceptor degeneration in the pig as an alternative model that shares features of the transgenic pig and human RP. METHODS. IAA blocks glycolysis, thereby inhibiting photoreceptor function. The effect of the intravenous injection of IAA on swine rod and cone photoreceptor viability and morphology was followed by histologic evaluation of different regions of the retina using hematoxylin and eosin and immunostaining. Rod and cone function was analyzed by full-field electroretinography and multifocal electroretinography. RESULTS. IAA led to specific loss of rods in a central-to-peripheral retinal gradient. Although cones were resistant, they showed shortened outer segments, loss of bipolar cell synaptic connections, and a diminished flicker ERG, hallmarks of transition to cone dysfunction in RP patients. CONCLUSIONS. IAA provides an alternative rod-dominant model of retinal damage that shares a surprising number of features with the pig transgenic model of RP and with human RP. This IAA model is cost-effective and rapid, ensuring that the size of the animals does not become prohibitive for end-stage evaluation or therapeutic intervention.

  4. Irreversible Capacities of Graphite in Low Temperature Electrolytes for Lithium-Ion Batteries

    NASA Technical Reports Server (NTRS)

    Ratnakumar, B.; Smart, M.; Surampudi, S.; Wang, Y.; Zhang, X.; Greenbaum, S.; Hightower, A.; Ahn, C.; Fultz, B.

    1999-01-01

    Carbonaceous anode materials in lithium ion rechargeable cells experience irreversible capacity, mainly due to a consumption of lithium in the formation of surface passive films. The stability and kinetics of lithium intercalation into the carbon anodes are dictated by these films.

  5. An ecology-based analysis of irreversible biofouling in membrane bioreactors.

    PubMed

    Zhang, K; Choi, H; Wu, M; Sorial, G A; Dionysiou, D; Oerther, D B

    2007-01-01

    To provide the first step towards a microbial ecology-based understanding of irreversible membrane biofouling, four laboratory-scale membrane bioreactors (MBRs) were operated to investigate the identity of bacterial populations highly correlated with irreversible membrane biofouling. The conventional MBR was divided into two separate experimental units. Unit one consisted of four suspended-growth, activated sludge, sequencing batch bioreactors treating a synthetic paper mill wastewater. Unit two consisted of a microfiltration membrane cell. Amplified ribosomal deoxyribonucleic acid restriction analysis (ARDRA) was used to compare the predominant bacterial populations in samples of mixed liquor and irreversibly bound to the membrane surface. The results of ARDRA showed a significant difference between the planktonic and sessile bacterial communities suggesting that irreversible biofouling of microfiltration membranes may be more highly correlated to specific bacterial populations rather than the total, bulk concentration of biomass. A custom-built mini-flow cell and light microscopy were used to visualise the early formation of biofilms by two pure cultures (Escherichia coli and Acinetobacter calcoaceticus) on membrane surfaces. The results confirmed that A. calcoaceticus was able to enhance the initiation of biofilm formation on microfiltration membranes.

  6. A comparison of the anesthetic efficacy of articaine and lidocaine in patients with irreversible pulpitis.

    PubMed

    Tortamano, Isabel Peixoto; Siviero, Marcelo; Costa, Carina Gisele; Buscariolo, Inês Aparecida; Armonia, Paschoal Laércio

    2009-02-01

    The purpose of the present study was to compare the anesthetic efficacy of 4% articaine with 1:100,000 epinephrine with that of 2% lidocaine with 1:100,000 epinephrine during pulpectomy in patients with irreversible pulpitis in mandibular posterior teeth. Forty volunteers, patients with irreversible pulpitis admitted to the Emergency Center of the School of Dentistry at the University of São Paulo, randomly received a conventional inferior alveolar nerve block containing 3.6 mL of either 4% articaine with 1:100,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine. During the subsequent pulpectomy, we recorded the patients' subjective assessments of lip anesthesia, the absence/presence of pulpal anesthesia through electric pulp stimulation, and the absence/presence of pain through a verbal analogue scale. All tested patients reported lip anesthesia after the application of either inferior alveolar nerve block. Regarding pulpal anesthesia success as measured with the pulp tester, the lidocaine solution had a higher success rate (70%) than the articaine solution (65%). For patients reporting none or mild pain during pulpectomy, the success rate of the articaine solution (65%) was higher than that of the lidocaine solution (45%). Yet, none of the observed differences between articaine and lidocaine were statistically significant. Apparently, therefore, both local anesthetic solutions had similar effects on the patients with irreversible pulpitis in mandibular posterior teeth. Neither of the solutions, however, resulted in an effective pain control during irreversible pulpitis treatments.

  7. Thermodynamics of Irreversible Processes. Physical Processes in Terrestrial and Aquatic Ecosystems, Transport Processes.

    ERIC Educational Resources Information Center

    Levin, Michael; Gallucci, V. F.

    These materials were designed to be used by life science students for instruction in the application of physical theory to ecosystem operation. Most modules contain computer programs which are built around a particular application of a physical process. This module describes the application of irreversible thermodynamics to biology. It begins with…

  8. The “irreversibility line” viewed as a phase transition: thermodynamic properties

    NASA Astrophysics Data System (ADS)

    Tournier, R.; Giordanengo, B.; De Rango, P.; Sulpice, A.

    1990-08-01

    The irreversibility line could be a second order phase transition. A vortex-lattice-dependent term in the Gibbs free energy is assumed to go to zero as H-H * for H < H *. The reversible magnetization of extremely high κ materials and H *(T) are used to predict the change of susceptibility and specific heat at the transition without any ajustable parameter.

  9. 50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act....

  10. 50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act....

  11. 50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act....

  12. 50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act....

  13. 50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act....

  14. Laser induced irreversible absorption changes in alkali halides at 10.6 µm

    NASA Astrophysics Data System (ADS)

    Wu, S.-T.; Bass, M.

    1981-12-01

    Laser induced irreversible changes in the absorption of alkali halides has been observed by using repetitively pulsed laser calorimetry. These changes occur at intensities below that required for laser induced breakdown and necessitate a change in the definition of laser damage threshold. A simple model is proposed to explain these observations based on the accumulation of microscopic failures as a result of each pulse.

  15. Irreversible magnetization reversal in some Co-based alloy thin films

    NASA Astrophysics Data System (ADS)

    Admon, U.; Dariel, M. P.; Grunbaum, E.; Lodder, J. C.

    1989-07-01

    Irreversible magnetization reversal occurs either by coherent or incoherent spin rotation or by wall displacement. In electrodeposited Co-W, Co-Fe, and Co-P 300-500-Å films, vibrating sample magnetometer hysteresis loop analyses indicate that magnetization reversal takes place by wall displacement. The formation and movement of domain walls has been put in evidence by Lorentz electron microscopy.

  16. Expansion Work without the External Pressure and Thermodynamics in Terms of Quasistatic Irreversible Processes

    ERIC Educational Resources Information Center

    Schmidt-Rohr, Klaus

    2014-01-01

    We demonstrate that the formula for irreversible expansion work in most chemical thermodynamics textbooks does not apply during the expansion process. Instead of the "external pressure" P[subscript ext], the pressure P[subscript sys,mb] on the piston or other moving boundary (hence the subscript mb), which is nearly equal to the system…

  17. Magnetic irreversibility: An important amendment in the zero-field-cooling and field-cooling method

    NASA Astrophysics Data System (ADS)

    Teixeira Dias, Fábio; das Neves Vieira, Valdemar; Esperança Nunes, Sabrina; Pureur, Paulo; Schaf, Jacob; Fernanda Farinela da Silva, Graziele; de Paiva Gouvêa, Cristol; Wolff-Fabris, Frederik; Kampert, Erik; Obradors, Xavier; Puig, Teresa; Roa Rovira, Joan Josep

    2016-02-01

    The present work reports about experimental procedures to correct significant deviations of magnetization data, caused by magnetic relaxation, due to small field cycling by sample transport in the inhomogeneous applied magnetic field of commercial magnetometers. The extensively used method for measuring the magnetic irreversibility by first cooling the sample in zero field, switching on a constant applied magnetic field and measuring the magnetization M(T) while slowly warming the sample, and subsequently measuring M(T) while slowly cooling it back in the same field, is very sensitive even to small displacement of the magnetization curve. In our melt-processed YBaCuO superconducting sample we observed displacements of the irreversibility limit up to 7 K in high fields. Such displacements are detected only on confronting the magnetic irreversibility limit with other measurements, like for instance zero resistance, in which the sample remains fixed and so is not affected by such relaxation. We measured the magnetic irreversibility, Tirr(H), using a vibrating sample magnetometer (VSM) from Quantum Design. The zero resistance data, Tc0(H), were obtained using a PPMS from Quantum Design. On confronting our irreversibility lines with those of zero resistance, we observed that the Tc0(H) data fell several degrees K above the Tirr(H) data, which obviously contradicts the well known properties of superconductivity. In order to get consistent Tirr(H) data in the H-T plane, it was necessary to do a lot of additional measurements as a function of the amplitude of the sample transport and extrapolate the Tirr(H) data for each applied field to zero amplitude.

  18. [Determination of irreversibility of clinical brain death. Electroencephalography and evoked potentials].

    PubMed

    Buchner, H; Ferbert, A

    2016-02-01

    Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

  19. Effect of hydraulically reversible and hydraulically irreversible fouling on the removal of MS2 and φX174 bacteriophage by an ultrafiltration membrane.

    PubMed

    ElHadidy, Ahmed M; Peldszus, Sigrid; Van Dyke, Michele I

    2014-09-15

    The effect of membrane fouling on the removal of enteric virus surrogates MS2 and φX174 bacteriophage by an ultrafiltration membrane was assessed under simulated full-scale drinking water treatment operating conditions. Filtration experiments of up to 8 days using either river or lake water ascertained how the membrane fouling layer affected virus removal. Organic carbon fractionation techniques identified potential foulants, including biopolymers, in the feed water and in the permeate. Hydraulically irreversible fouling could greatly improve the removal of both viruses at moderate and severe fouling conditions by up to 2.5 logs. Hydraulically reversible fouling increased virus removal only slightly, and increased removal of >0.5 log for both phage were only obtained under severe fouling conditions. The increase in virus removal due to irreversible and reversible fouling differed between the two water sources. As the degree of fouling increased, differences between the removal of the two phage decreased. Maintenance cleaning partially removed membrane foulants, however virus removal following maintenance cleaning was lower than that of the fouled membrane, it remained higher than that of the clean membrane.

  20. Analysis of Ribosome Inactivating Protein (RIP): A Bioinformatics Approach

    NASA Astrophysics Data System (ADS)

    Jothi, G. Edward Gnana; Majilla, G. Sahaya Jose; Subhashini, D.; Deivasigamani, B.

    2012-10-01

    In spite of the medical advances in recent years, the world is in need of different sources to encounter certain health issues.Ribosome Inactivating Proteins (RIPs) were found to be one among them. In order to get easy access about RIPs, there is a need to analyse RIPs towards constructing a database on RIPs. Also, multiple sequence alignment was done towards screening for homologues of significant RIPs from rare sources against RIPs from easily available sources in terms of similarity. Protein sequences were retrieved from SWISS-PROT and are further analysed using pair wise and multiple sequence alignment.Analysis shows that, 151 RIPs have been characterized to date. Amongst them, there are 87 type I, 37 type II, 1 type III and 25 unknown RIPs. The sequence length information of various RIPs about the availability of full or partial sequence was also found. The multiple sequence alignment of 37 type I RIP using the online server Multalin, indicates the presence of 20 conserved residues. Pairwise alignment and multiple sequence alignment of certain selected RIPs in two groups namely Group I and Group II were carried out and the consensus level was found to be 98%, 98% and 90% respectively.

  1. Development of methods to measure virus inactivation in fresh waters.

    PubMed Central

    Ward, R L; Winston, P E

    1985-01-01

    This study concerns the identification and correction of deficiencies in methods used to measure inactivation rates of enteric viruses seeded into environmental waters. It was found that viable microorganisms in an environmental water sample increased greatly after addition of small amounts of nutrients normally present in the unpurified seed virus preparation. This burst of microbial growth was not observed after seeding the water with purified virus. The use of radioactively labeled poliovirus revealed that high percentages of virus particles, sometimes greater than 99%, were lost through adherence to containers, especially in less turbid waters. This effect was partially overcome by the use of polypropylene containers and by the absence of movement during incubation. Adherence to containers clearly demonstrated the need for labeled viruses to monitor losses in this type of study. Loss of viral infectivity in samples found to occur during freezing was avoided by addition of broth. Finally, microbial contamination of the cell cultures during infectivity assays was overcome by the use of gentamicin and increased concentrations of penicillin, streptomycin, and amphotericin B. PMID:3004328

  2. Total and Partial Laser Arytenoidectomy for Bilateral Vocal Fold Paralysis.

    PubMed

    Yılmaz, Taner; Altuntaş, Ozan Muzaffer; Süslü, Nilda; Atay, Gamze; Özer, Serdar; Kuşçu, Oğuz; Sözen, Tevfik

    2016-01-01

    Introduction. Treatment for bilateral vocal fold paralysis (BVFP) has evolved from external irreversible procedures to endolaryngeal laser surgery with greater focus on anatomic and functional preservation. Since the introduction of endolaryngeal laser arytenoidectomy, certain modifications have been described, such as partial resection procedures and mucosa sparing techniques as opposed to total arytenoidectomy. Discussion. The primary outcome measure in studies on BVFP treatment using total or partial arytenoidectomy is avoidance of tracheotomy or decannulation and reported success ranges between 90 and 100% in this regard. Phonation is invariably affected and arytenoidectomy worsens both aerodynamic and acoustic vocal properties. Recent reports indicate that partial and total arytenoidectomies have similar outcome in respect to phonation and swallowing. We use CO2 laser assisted partial arytenoidectomy with a posteromedially based mucosal flap for primary cases and reserve total arytenoidectomy for revision. Lateral suturing of preserved mucosa provides tension on the vocal fold leading to better voice and leaves no raw surgical field to unpredictable scarring or granulation. Conclusion. Arytenoidectomy as a permanent static procedure remains a traditional yet sound choice in the treatment of BVFP. Laser dissection provides a precise dissection in a narrow surgical field and the possibility to perform partial arytenoidectomy.

  3. Total and Partial Laser Arytenoidectomy for Bilateral Vocal Fold Paralysis

    PubMed Central

    Süslü, Nilda; Atay, Gamze; Özer, Serdar; Kuşçu, Oğuz; Sözen, Tevfik

    2016-01-01

    Introduction. Treatment for bilateral vocal fold paralysis (BVFP) has evolved from external irreversible procedures to endolaryngeal laser surgery with greater focus on anatomic and functional preservation. Since the introduction of endolaryngeal laser arytenoidectomy, certain modifications have been described, such as partial resection procedures and mucosa sparing techniques as opposed to total arytenoidectomy. Discussion. The primary outcome measure in studies on BVFP treatment using total or partial arytenoidectomy is avoidance of tracheotomy or decannulation and reported success ranges between 90 and 100% in this regard. Phonation is invariably affected and arytenoidectomy worsens both aerodynamic and acoustic vocal properties. Recent reports indicate that partial and total arytenoidectomies have similar outcome in respect to phonation and swallowing. We use CO2 laser assisted partial arytenoidectomy with a posteromedially based mucosal flap for primary cases and reserve total arytenoidectomy for revision. Lateral suturing of preserved mucosa provides tension on the vocal fold leading to better voice and leaves no raw surgical field to unpredictable scarring or granulation. Conclusion. Arytenoidectomy as a permanent static procedure remains a traditional yet sound choice in the treatment of BVFP. Laser dissection provides a precise dissection in a narrow surgical field and the possibility to perform partial arytenoidectomy. PMID:27830141

  4. Chlorine inactivation of Tubifex tubifex in drinking water and the synergistic effect of sequential inactivation with UV irradiation and chlorine.

    PubMed

    Nie, Xiao-Bao; Li, Zhi-Hong; Long, Yuan-Nan; He, Pan-Pan; Xu, Chao

    2017-06-01

    The inactivation of Tubifex tubifex is important to prevent contamination of drinking water. Chlorine is a widely-used disinfectant and the key factor in the inactivation of T. tubifex. This study investigated the inactivation kinetics of chlorine on T. tubifex and the synergistic effect of the sequential use of chlorine and UV irradiation. The experimental results indicated that the Ct (concentration × timereaction) concept could be used to evaluate the inactivation kinetics of T. tubifex with chlorine, thus allowing for the use of a simpler Ct approach for the assessment of T. tubifex chlorine inactivation requirements. The inactivation kinetics of T. tubifex by chlorine was found to be well-fitted to a delayed pseudo first-order Chick-Watson expression. Sequential experiments revealed that UV irradiation and chlorine worked synergistically to effectively inactivate T. tubifex as a result of the decreased activation energy, Ea, induced by primary UV irradiation. Furthermore, the inactivation effectiveness of T. tubifex by chlorine was found to be affected by several drinking water quality parameters including pH, turbidity, and chemical oxygen demand with potassium permanganate (CODMn) concentration. High pH exhibited pronounced inactivation effectiveness and the decrease in turbidity and CODMn concentrations contributed to the inactivation of T. tubifex.

  5. Oxygen partial pressure sensor

    DOEpatents

    Dees, D.W.

    1994-09-06

    A method for detecting oxygen partial pressure and an oxygen partial pressure sensor are provided. The method for measuring oxygen partial pressure includes contacting oxygen to a solid oxide electrolyte and measuring the subsequent change in electrical conductivity of the solid oxide electrolyte. A solid oxide electrolyte is utilized that contacts both a porous electrode and a nonporous electrode. The electrical conductivity of the solid oxide electrolyte is affected when oxygen from an exhaust stream permeates through the porous electrode to establish an equilibrium of oxygen anions in the electrolyte, thereby displacing electrons throughout the electrolyte to form an electron gradient. By adapting the two electrodes to sense a voltage potential between them, the change in electrolyte conductivity due to oxygen presence can be measured. 1 fig.

  6. Oxygen partial pressure sensor

    DOEpatents

    Dees, Dennis W.

    1994-01-01

    A method for detecting oxygen partial pressure and an oxygen partial pressure sensor are provided. The method for measuring oxygen partial pressure includes contacting oxygen to a solid oxide electrolyte and measuring the subsequent change in electrical conductivity of the solid oxide electrolyte. A solid oxide electrolyte is utilized that contacts both a porous electrode and a nonporous electrode. The electrical conductivity of the solid oxide electrolyte is affected when oxygen from an exhaust stream permeates through the porous electrode to establish an equilibrium of oxygen anions in the electrolyte, thereby displacing electrons throughout the electrolyte to form an electron gradient. By adapting the two electrodes to sense a voltage potential between them, the change in electrolyte conductivity due to oxygen presence can be measured.

  7. Methanol partial oxidation reformer

    DOEpatents

    Ahmed, Shabbir; Kumar, Romesh; Krumpelt, Michael

    1999-01-01

    A partial oxidation reformer comprising a longitudinally extending chamber having a methanol, water and an air inlet and an outlet. An igniter mechanism is near the inlets for igniting a mixture of methanol and air, while a partial oxidation catalyst in the chamber is spaced from the inlets and converts methanol and oxygen to carbon dioxide and hydrogen. Controlling the oxygen to methanol mole ratio provides continuous slightly exothermic partial oxidation reactions of methanol and air producing hydrogen gas. The liquid is preferably injected in droplets having diameters less than 100 micrometers. The reformer is useful in a propulsion system for a vehicle which supplies a hydrogen-containing gas to the negative electrode of a fuel cell.

  8. Methanol partial oxidation reformer

    DOEpatents

    Ahmed, S.; Kumar, R.; Krumpelt, M.

    1999-08-17

    A partial oxidation reformer is described comprising a longitudinally extending chamber having a methanol, water and an air inlet and an outlet. An igniter mechanism is near the inlets for igniting a mixture of methanol and air, while a partial oxidation catalyst in the chamber is spaced from the inlets and converts methanol and oxygen to carbon dioxide and hydrogen. Controlling the oxygen to methanol mole ratio provides continuous slightly exothermic partial oxidation reactions of methanol and air producing hydrogen gas. The liquid is preferably injected in droplets having diameters less than 100 micrometers. The reformer is useful in a propulsion system for a vehicle which supplies a hydrogen-containing gas to the negative electrode of a fuel cell. 7 figs.

  9. Methanol partial oxidation reformer

    DOEpatents

    Ahmed, S.; Kumar, R.; Krumpelt, M.

    1999-08-24

    A partial oxidation reformer is described comprising a longitudinally extending chamber having a methanol, water and an air inlet and an outlet. An igniter mechanism is near the inlets for igniting a mixture of methanol and air, while a partial oxidation catalyst in the chamber is spaced from the inlets and converts methanol and oxygen to carbon dioxide and hydrogen. Controlling the oxygen to methanol mole ratio provides continuous slightly exothermic partial oxidation reactions of methanol and air producing hydrogen gas. The liquid is preferably injected in droplets having diameters less than 100 micrometers. The reformer is useful in a propulsion system for a vehicle which supplies a hydrogen-containing gas to the negative electrode of a fuel cell. 7 figs.

  10. Methanol partial oxidation reformer

    DOEpatents

    Ahmed, Shabbir; Kumar, Romesh; Krumpelt, Michael

    2001-01-01

    A partial oxidation reformer comprising a longitudinally extending chamber having a methanol, water and an air inlet and an outlet. An igniter mechanism is near the inlets for igniting a mixture of methanol and air, while a partial oxidation catalyst in the chamber is spaced from the inlets and converts methanol and oxygen to carbon dioxide and hydrogen. Controlling the oxygen to methanol mole ratio provides continuous slightly exothermic partial oxidation reactions of methanol and air producing hydrogen gas. The liquid is preferably injected in droplets having diameters less than 100 micrometers. The reformer is useful in a propulsion system for a vehicle which supplies a hydrogen-containing gas to the negative electrode of a fuel cell.

  11. Identifying and characterizing binding sites on the irreversible inhibition of human glutathione S-transferase P1-1 by S-thiocarbamoylation.

    PubMed

    Quesada-Soriano, Indalecio; Primavera, Alessandra; Casas-Solvas, Juan M; Téllez-Sanz, Ramiro; Barón, Carmen; Vargas-Berenguel, Antonio; Lo Bello, Mario; García-Fuentes, Luís

    2012-07-23

    Human glutathione S-transferase P1-1 (hGST P1-1) is involved in cell detoxification processes through the conjugation of its natural substrate, reduced glutathione (GSH), with xenobiotics. GSTs are known to be overexpressed in tumors, and naturally occurring isothiocyanates, such as benzyl isothiocyanate (BITC), are effective cancer chemopreventive compounds. To identify and characterize the potential inhibitory mechanisms of GST P1-1 induced by isothiocyanate conjugates, we studied the binding of GST P1-1 and some cysteine mutants to the BITC-SG conjugate as well as to the synthetic S-(N-benzylcarbamoylmethyl)glutathione conjugate (BC-SG). We report here the inactivation of GST P1-1 through the covalent modification of two Cys47 residues per dimer and one Cys101. The evidence has been compiled by isothermal titration calorimetry (ITC) and electrospray ionization mass spectrometry (ESI-MS). ITC experiments suggest that the BITC-SG conjugate generates adducts with Cys47 and Cys101 at physiological temperatures through a corresponding kinetic process, in which the BITC moiety is covalently bound to these enzyme cysteines through an S-thiocarbamoylation reaction. ESI-MS analysis of the BITC-SG incubated enzymes indicates that although the Cys47 in each subunit is covalently attached to the BITC ligand moiety, only one of the Cys101 residues in the dimer is so attached. A plausible mechanism is given for the emergence of inactivation through the kinetic processes with both cysteines. Likewise, our molecular docking simulations suggest that steric hindrance is the reason why only one Cys101 per dimer is covalently modified by BITC-SG. No covalent inactivation of GST P1-1 with the BC-SG inhibitor has been observed. The affinities and inhibitory potencies for both conjugates are high and very similar, but slightly lower for BC-SG. Thus, we conclude that the presence of the sulfur atom from the isothiocyanate moiety in BITC-SG is crucial for its irreversible inhibition of

  12. Virus inactivation by protein denaturants used in affinity chromatography.

    PubMed

    Roberts, Peter L; Lloyd, David

    2007-10-01

    Virus inactivation by a number of protein denaturants commonly used in gel affinity chromatography for protein elution and gel recycling has been investigated. The enveloped viruses Sindbis, herpes simplex-1 and vaccinia, and the non-enveloped virus polio-1 were effectively inactivated by 0.5 M sodium hydroxide, 6 M guanidinium thiocyanate, 8 M urea and 70% ethanol. However, pH 2.6, 3 M sodium thiocyanate, 6 M guanidinium chloride and 20% ethanol, while effectively inactivating the enveloped viruses, did not inactivate polio-1. These studies demonstrate that protein denaturants are generally effective for virus inactivation but with the limitation that only some may inactivate non-enveloped viruses. The use of protein denaturants, together with virus reduction steps in the manufacturing process should ensure that viral cross contamination between manufacturing batches of therapeutic biological products is prevented and the safety of the product ensured.

  13. Obatoclax interacts synergistically with the irreversible proteasome inhibitor carfilzomib in GC- and ABC-DLBCL cells in vitro and in vivo.

    PubMed

    Dasmahapatra, Girija; Lembersky, Dmitry; Son, Minkyeong P; Patel, Hiral; Peterson, Derick; Attkisson, Elisa; Fisher, Richard I; Friedberg, Jonathan W; Dent, Paul; Grant, Steven

    2012-05-01

    Interactions between the irreversible proteasome inhibitor carfilzomib and the pan-BH3 mimetic obatoclax were examined in germinal center (GC)- and activated B-cell-diffuse large B-cell lymphoma (ABC-DLBCL) cells. Cotreatment with minimally toxic concentrations of carfilzomib (i.e., 2-6 nmol/L) and subtoxic concentrations of obatoclax (0.05-2.0 μmol/L) synergistically increased apoptosis in multiple DLBCL cell lines and increased lethality toward primary human DLBCL but not normal CD34(+) cells. Synergistic interactions were associated with sharp increases in caspase-3 activation, PARP cleavage, p-JNK induction, upregulation of Noxa, and AKT dephosphorylation. Combined treatment also diminished carfilzomib-mediated Mcl-1 upregulation whereas immunoprecipitation analysis revealed reduced associations between Bak and Mcl-1/Bcl-xL and Bim and Mcl-1. The carfilzomib/obatoclax regimen triggered translocation, conformational change, and dimerization of Bax and activation of Bak. Genetic interruption of c-jun-NH(2)-kinase (JNK) and Noxa by short hairpin RNA knockdown, ectopic Mcl-1 expression, or enforced activation of AKT significantly attenuated carfilzomib/obatoclax-mediated apoptosis. Notably, coadministration of carfilzomib/obatoclax sharply increased apoptosis in multiple bortezomib-resistant DLBCL models. Finally, in vivo administration of carfilzomib and obatoclax to mice inoculated with SUDHL4 cells substantially suppressed tumor growth, activated JNK, inactivated AKT, and increased survival compared with the effects of single-agent treatment. Together, these findings argue that a strategy combining carfilzomib and obatoclax warrants attention in DLBCL.

  14. Survey of Impression Materials and Techniques in Fixed Partial Dentures among the Practitioners in India.

    PubMed

    Moldi, Arvind; Gala, Vimal; Puranik, Shivakumar; Karan, Smita; Deshpande, Sumit; Neela, Neelima

    2013-01-01

    Objective. Anecdotal evidence suggests that impression materials and techniques used in general dental practice for fixed partial dentures vary from those taught in dental schools. The aim of this survey was to integrate impression techniques evolved all over the years for fixed partial dentures and to know the techniques and materials which are used in the present day by the practitioners. Materials and Methods. A total of 1000 questionnaires were sent to various practitioners in India, out of which 807 questionnaires were filled. Results. The results showed that 84.8% of prosthodontists (65.56%, urban areas) use elastomeric impression materials as well as irreversible hydrocolloids and 15.2% use irreversible hydrocolloid only. Amongst other practitioners, 55.46% use irreversible hydrocolloid (45%, rural and semiurban areas) and 44.54% use elastomeric impression materials. Elastomeric impression technique practiced most commonly is putty reline with/without spacer (77.2%); other techniques are multiple-mix and monophase techniques. Conclusion. The ideal materials, technique, and armamentarium are required for the long-term success of the treatment for fixed partial denture. Also, if the ideal procedure is not followed, it will lead to a compromised fit of the final prosthesis and failure of the treatment.

  15. Partially strong WW scattering

    SciTech Connect

    Cheung Kingman; Chiang Chengwei; Yuan Tzuchiang

    2008-09-01

    What if only a light Higgs boson is discovered at the CERN LHC? Conventional wisdom tells us that the scattering of longitudinal weak gauge bosons would not grow strong at high energies. However, this is generally not true. In some composite models or general two-Higgs-doublet models, the presence of a light Higgs boson does not guarantee complete unitarization of the WW scattering. After partial unitarization by the light Higgs boson, the WW scattering becomes strongly interacting until it hits one or more heavier Higgs bosons or other strong dynamics. We analyze how LHC experiments can reveal this interesting possibility of partially strong WW scattering.

  16. Irreversible Heating Measurement with Microsecond Pulse Magnet: Example of the α-θ Phase Transition of Solid Oxygen

    NASA Astrophysics Data System (ADS)

    Nomura, Toshihiro; Matsuda, Yasuhiro H.; Takeyama, Shojiro; Kobayashi, Tatsuo C.

    2016-09-01

    Dissipation inevitably occurs in first-order phase transitions, leading to irreversible heating. Conversely, the irreversible heating effect may indicate the occurrence of the first-order phase transition. We measured the temperature change at the magnetic-field-induced α-θ phase transition of solid oxygen. A significant temperature increase from 13 to 37 K, amounting to 700 J/mol, due to irreversible heating was observed at the first-order phase transition. We argue that the hysteresis loss of the magnetization curve and the dissipative structural transformation account for the irreversible heating. The measurement of irreversible heating can be utilized to detect the first-order phase transition in combination with an ultrahigh magnetic fields generated in a time of µs order.

  17. Antibacterial efficacy and effect of Morinda citrifolia L. mixed with irreversible hydrocolloid for dental impressions: A randomized controlled trial

    PubMed Central

    Ahmed, A. Shafath; Charles, P. David; Cholan, R.; Russia, M.; Surya, R.; Jailance, L.

    2015-01-01

    Aim: This study aimed to evaluate whether the extract of Morinda citrifolia L. mixed with irreversible hydrocolloid powder decreases microbial contamination during impression making without affecting the resulting casts. Materials and Methods: Twenty volunteers were randomly divided into two groups (n = 10). Group A 30 ml extract of M. citrifolia L diluted in 30 ml of water was mixed to make the impression with irreversible hydrocolloid material. Group B 30 ml deionized water was mixed with irreversible hydrocolloid material to make the impressions following which the surface roughness and dimensional stability of casts were evaluated. Results: Extract of M. citrifolia L. mixed with irreversible hydrocolloid decreased the percentage of microorganisms when compared with water (P < 0.001) but did not affect the surface quality or dimensional stability of the casts. Conclusion: Mixing the extract of M. citrifolia L. with irreversible hydrocolloid powder is an alternative method to prevent contamination without sacrificing impression quality. PMID:26538926

  18. Inactivation of human norovirus using chemical sanitizers.

    PubMed

    Kingsley, David H; Vincent, Emily M; Meade, Gloria K; Watson, Clytrice L; Fan, Xuetong

    2014-02-03

    The porcine gastric mucin binding magnetic bead (PGM-MB) assay was used to evaluate the ability of chlorine, chlorine dioxide, peroxyacetic acid, hydrogen peroxide, and trisodium phosphate to inactivate human norovirus within 10% stool filtrate. One-minute free chlorine treatments at concentrations of 33 and 189 ppm reduced virus binding in the PGM-MB assay by 1.48 and 4.14 log₁₀, respectively, suggesting that chlorine is an efficient sanitizer for inactivation of human norovirus (HuNoV). Five minute treatments with 5% trisodium phosphate (pH~12) reduced HuNoV binding by 1.6 log₁₀, suggesting that TSP, or some other high pH buffer, could be used to treat food and food contact surfaces to reduce HuNoV. One minute treatments with 350 ppm chlorine dioxide dissolved in water did not reduce PGM-MB binding, suggesting that the sanitizer may not be suitable for HuNoV inactivation in liquid form. However a 60-min treatment with 350 ppm chlorine dioxide did reduce human norovirus by 2.8 log₁₀, indicating that chlorine dioxide had some, albeit limited, activity against HuNoV. Results also suggest that peroxyacetic acid has limited effectiveness against human norovirus, since 1-min treatments with up to 195 ppm reduced human norovirus binding by <1 log₁₀. Hydrogen peroxide (4%) treatment of up to 60 min resulted in minimal binding reduction (~0.1 log₁₀) suggesting that H₂O₂ is not a good liquid sanitizer for HuNoV. Overall this study suggests that HuNoV is remarkably resistant to several commonly used disinfectants and advocates for the use of chlorine (sodium hypochlorite) as a HuNoV disinfectant wherever possible.

  19. Assessing the role of feed water constituents in irreversible membrane fouling of pilot-scale ultrafiltration drinking water treatment systems.

    PubMed

    Peiris, R H; Jaklewicz, M; Budman, H; Legge, R L; Moresoli, C

    2013-06-15

    Fluorescence excitation-emission matrix (EEM) approach together with principal component analysis (PCA) was used for assessing hydraulically irreversible fouling of three pilot-scale ultrafiltration (UF) systems containing full-scale and bench-scale hollow fiber membrane modules in drinking water treatment. These systems were operated for at least three months with extensive cycles of permeation, combination of back-pulsing and scouring and chemical cleaning. The principal component (PC) scores generated from the PCA of the fluorescence EEMs were found to be related to humic substances (HS), protein-like and colloidal/particulate matter content. PC scores of HS- and protein-like matter of the UF feed water, when considered separately, showed reasonably good correlations with the rate of hydraulically irreversible fouling for long-term UF operations. In contrast, comparatively weaker correlations for PC scores of colloidal/particulate matter and the rate of hydraulically irreversible fouling were obtained for all UF systems. Since, individual correlations could not fully explain the evolution of the rate of irreversible fouling, multi-linear regression models were developed to relate the combined effect of HS-like, protein-like and colloidal/particulate matter PC scores to the rate of hydraulically irreversible fouling for each specific UF system. These multi-linear regression models revealed significant individual and combined contribution of HS- and protein-like matter to the rate of hydraulically irreversible fouling, with protein-like matter generally showing the greatest contribution. The contribution of colloidal/particulate matter to the rate of hydraulically irreversible fouling was not as significant. The addition of polyaluminum chloride, as coagulant, to UF feed appeared to have a positive impact in reducing hydraulically irreversible fouling by these constituents. The proposed approach has applications in quantifying the individual and synergistic

  20. Inactivation of virus in solution by cold atmospheric pressure plasma: identification of chemical inactivation pathways

    NASA Astrophysics Data System (ADS)

    Aboubakr, Hamada A.; Gangal, Urvashi; Youssef, Mohammed M.; Goyal, Sagar M.; Bruggeman, Peter J.

    2016-05-01

    Cold atmospheric pressure plasma (CAP) inactivates bacteria and virus through in situ production of reactive oxygen and nitrogen species (RONS). While the bactericidal and virucidal efficiency of plasmas is well established, there is limited knowledge about the chemistry leading to the pathogen inactivation. This article describes a chemical analysis of the CAP reactive chemistry involved in the inactivation of feline calicivirus. We used a remote radio frequency CAP produced in varying gas mixtures leading to different plasma-induced chemistries. A study of the effects of selected scavengers complemented with positive control measurements of relevant RONS reveal two distinctive pathways based on singlet oxygen and peroxynitrous acid. The first mechanism is favored in the presence of oxygen and the second in the presence of air when a significant pH reduction is induced in the solution by the plasma. Additionally, smaller effects of the H2O2, O3 and \\text{NO}2- produced were also found. Identification of singlet oxygen-mediated 2-imidazolone/2-oxo-His (His  +14 Da)—an oxidative modification of His 262 comprising the capsid protein of feline calicivirus links the plasma induced singlet oxygen chemistry to viral inactivation.

  1. Species-specific differences in X chromosome inactivation in mammals.

    PubMed

    Sado, Takashi; Sakaguchi, Takehisa

    2013-10-01

    In female mammals, the dosage difference in X-linked genes between XX females and XY males is compensated for by inactivating one of the two X chromosomes during early development. Since the discovery of the X inactive-specific transcript (XIST) gene in humans and its subsequent isolation of the mouse homolog, Xist, in the early 1990s, the molecular basis of X chromosome inactivation (X-inactivation) has been more fully elucidated using genetically manipulated mouse embryos and embryonic stem cells. Studies on X-inactivation in other mammals, although limited when compared with those in the mice, have revealed that, while their inactive X chromosome shares many features with those in the mice, there are marked differences in not only some epigenetic modifications of the inactive X chromosome but also when and how X-inactivation is initiated during early embryonic development. Such differences raise the issue about what extent of the molecular basis of X-inactivation in the mice is commonly shared among others. Recognizing similarities and differences in X-inactivation among mammals may provide further insight into our understanding of not only the evolutionary but also the molecular aspects for the mechanism of X-inactivation. Here, we reviewed species-specific differences in X-inactivation and discussed what these differences may reveal.

  2. Partial polarizer filter

    NASA Technical Reports Server (NTRS)

    Title, A. M. (Inventor)

    1978-01-01

    A birefringent filter module comprises, in seriatum. (1) an entrance polarizer, (2) a first birefringent crystal responsive to optical energy exiting the entrance polarizer, (3) a partial polarizer responsive to optical energy exiting the first polarizer, (4) a second birefringent crystal responsive to optical energy exiting the partial polarizer, and (5) an exit polarizer. The first and second birefringent crystals have fast axes disposed + or -45 deg from the high transmitivity direction of the partial polarizer. Preferably, the second crystal has a length 1/2 that of the first crystal and the high transmitivity direction of the partial polarizer is nine times as great as the low transmitivity direction. To provide tuning, the polarizations of the energy entering the first crystal and leaving the second crystal are varied by either rotating the entrance and exit polarizers, or by sandwiching the entrance and exit polarizers between pairs of half wave plates that are rotated relative to the polarizers. A plurality of the filter modules may be cascaded.

  3. Dilemmas of partial cooperation.

    PubMed

    Stark, Hans-Ulrich

    2010-08-01

    Related to the often applied cooperation models of social dilemmas, we deal with scenarios in which defection dominates cooperation, but an intermediate fraction of cooperators, that is, "partial cooperation," would maximize the overall performance of a group of individuals. Of course, such a solution comes at the expense of cooperators that do not profit from the overall maximum. However, because there are mechanisms accounting for mutual benefits after repeated interactions or through evolutionary mechanisms, such situations can constitute "dilemmas" of partial cooperation. Among the 12 ordinally distinct, symmetrical 2 x 2 games, three (barely considered) variants are correspondents of such dilemmas. Whereas some previous studies investigated particular instances of such games, we here provide the unifying framework and concisely relate it to the broad literature on cooperation in social dilemmas. Complementing our argumentation, we study the evolution of partial cooperation by deriving the respective conditions under which coexistence of cooperators and defectors, that is, partial cooperation, can be a stable outcome of evolutionary dynamics in these scenarios. Finally, we discuss the relevance of such models for research on the large biodiversity and variation in cooperative efforts both in biological and social systems.

  4. Inactivation of Toluene 2-Monooxygenase in Burkholderia cepacia G4 by Alkynes

    PubMed Central

    Yeager, Chris M.; Bottomley, Peter J.; Arp, Daniel J.; Hyman, Michael R.

    1999-01-01

    High concentrations of acetylene (10 to 50% [vol/vol] gas phase) were required to inhibit the growth of Burkholderia cepacia G4 on toluene, while 1% (vol/vol) (gas phase) propyne or 1-butyne completely inhibited growth. Low concentrations of longer-chain alkynes (C5 to C10) were also effective inhibitors of toluene-dependent growth, and 2- and 3-alkynes were more potent inhibitors than their 1-alkyne counterparts. Exposure of toluene-grown B. cepacia G4 to alkynes resulted in the irreversible loss of toluene- and o-cresol-dependent O2 uptake activities, while acetate- and 3-methylcatechol-dependent O2 uptake activities were unaffected. Toluene-dependent O2 uptake decreased upon the addition of 1-butyne in a concentration- and time-dependent manner. The loss of activity followed first-order kinetics, with apparent rate constants ranging from 0.25 min−1 to 2.45 min−1. Increasing concentrations of toluene afforded protection from the inhibitory effects of 1-butyne. Furthermore, oxygen, supplied as H2O2, was required for inhibition by 1-butyne. These results suggest that alkynes are specific, mechanism-based inactivators of toluene 2-monooxygenase in B. cepacia G4, although the simplest alkyne, acetylene, was relatively ineffective compared to longer alkynes. Alkene analogs of acetylene and propyne—ethylene and propylene—were not inactivators of toluene 2-monooxygenase activity in B. cepacia G4 but were oxidized to their respective epoxides, with apparent Ks and Vmax values of 39.7 μM and 112.3 nmol min−1 mg of protein−1 for ethylene and 32.3 μM and 89.2 nmol min−1 mg of protein−1 for propylene. PMID:9925593

  5. Direct evidence for the covalent modification of glutathione-S-transferase P1-1 by electrophilic prostaglandins: implications for enzyme inactivation and cell survival.

    PubMed

    Sánchez-Gómez, Francisco J; Gayarre, Javier; Avellano, M Isabel; Pérez-Sala, Dolores

    2007-01-15

    Glutathione-S-transferases (GST) catalyze the conjugation of electrophilic compounds to glutathione, thus playing a key role in cell survival and tumor chemoresistance. Cyclopentenone prostaglandins (cyPG) are electrophilic eicosanoids that display potent antiproliferative properties, through multiple mechanisms not completely elucidated. Here we show that the cyPG 15-deoxy-Delta(12,14)-PGJ2 (15d-PGJ2) binds to GSTP1-1 covalently, as demonstrated by mass spectrometry and by the use of biotinylated 15d-PGJ2. Moreover, cyPG inactivate GSTP1-1 irreversibly. The presence of the cyclopentenone moiety is important for these effects. Covalent interactions also occur in cells, in which 15d-PGJ2 binds to endogenous GSTP1-1, irreversibly reduces GST free-thiol content and inhibits GST activity. Protein delivery of GSTP1-1 improves cell survival upon serum deprivation whereas 15d-PGJ2-treated GSTP1-1 displays a reduced protective effect. These results show the first evidence for the formation of stable adducts between cyPG and GSTP1-1 and may offer new perspectives for the development of irreversible GST inhibitors as anticancer agents.

  6. Short communication: Pasteurization as a means of inactivating staphylococcal enterotoxins A, B, and C in milk.

    PubMed

    Necidova, Lenka; Bogdanovicova, Katerina; Harustiakova, Danka; Bartova, Katerina

    2016-11-01

    Our aim was to assess the effect of pasteurization temperature on inactivation of staphylococcal enterotoxins (SE). Milk samples were inoculated with log 4.38 to 5.18cfu/mL of 40 different Staphylococcus aureus strains having the ability to produce types A, B, or C SE and incubated at 37°C for 24h to develop SE. This incubation was followed by heat treatment for 15 s at 72, 85, and 92°C. Samples were analyzed for Staph. aureus count by plate method and, specifically, for SE presence. An enzyme-linked immunofluorescent assay on a MiniVIDAS analyzer (bioMérieux, Marcy l'Étoile, France) was used to detect SE, which were determined semiquantitatively based on test values. The Staph. aureus count in milk before pasteurization did not affect the amount of SE. Before pasteurization, SEB was detected in the lowest amount compared with other SE types. Staphylococcal enterotoxins were markedly reduced with pasteurization and inactivated at pasteurization temperatures to an extent depending on the amount in the sample before pasteurization. After pasteurization at 72°C, SE were detected in 87.5% of samples (35/40), after pasteurization at 85°C in 52.5% of samples (21/40), and after pasteurization at 92°C in 45.0% of samples (18/40). We determined that SE may still persist in milk even when Staph. aureus bacteria are inactivated through pasteurization. Although pasteurization may partially inactivate SE in milk, a key measure in the prevention of staphylococcal enterotoxicosis linked to pasteurized milk consumption is to avoid any cold chain disruption during milk production and processing.

  7. Kinetic Features of L,D-Transpeptidase Inactivation Critical for β-Lactam Antibacterial Activity

    PubMed Central

    Lecoq, Lauriane; Bougault, Catherine; Mainardi, Jean-Luc; Rice, Louis B.; Ethève-Quelquejeu, Mélanie; Gutmann, Laurent; Marie, Arul; Dubost, Lionel; Hugonnet, Jean-Emmanuel; Simorre, Jean-Pierre; Arthur, Michel

    2013-01-01

    Active-site serine D,D-transpeptidases belonging to the penicillin-binding protein family (PBPs) have been considered for a long time as essential for peptidoglycan cross-linking in all bacteria. However, bypass of the PBPs by an L,D-transpeptidase (Ldtfm) conveys high-level resistance to β-lactams of the penam class in Enterococcus faecium with a minimal inhibitory concentration (MIC) of ampicillin >2,000 µg/ml. Unexpectedly, Ldtfm does not confer resistance to β-lactams of the carbapenem class (imipenem MIC = 0.5 µg/ml) whereas cephems display residual activity (ceftriaxone MIC = 128 µg/ml). Mass spectrometry, fluorescence kinetics, and NMR chemical shift perturbation experiments were performed to explore the basis for this specificity and identify β-lactam features that are critical for efficient L,D-transpeptidase inactivation. We show that imipenem, ceftriaxone, and ampicillin acylate Ldtfm by formation of a thioester bond between the active-site cysteine and the β-lactam-ring carbonyl. However, slow acylation and slow acylenzyme hydrolysis resulted in partial Ldtfm inactivation by ampicillin and ceftriaxone. For ampicillin, Ldtfm acylation was followed by rupture of the C5–C6 bond of the β-lactam ring and formation of a secondary acylenzyme prone to hydrolysis. The saturable step of the catalytic cycle was the reversible formation of a tetrahedral intermediate (oxyanion) without significant accumulation of a non-covalent complex. In agreement, a derivative of Ldtfm blocked in acylation bound ertapenem (a carbapenem), ceftriaxone, and ampicillin with similar low affinities. Thus, oxyanion and acylenzyme stabilization are both critical for rapid L,D-transpeptidase inactivation and antibacterial activity. These results pave the way for optimization of the β-lactam scaffold for L,D-transpeptidase-inactivation. PMID:23861815

  8. Atmospheric pressure resistive barrier air plasma jet induced bacterial inactivation in aqueous environment

    NASA Astrophysics Data System (ADS)

    Thiyagarajan, Magesh; Sarani, Abdollah; Gonzales, Xavier

    2013-03-01

    An atmospheric pressure resistive barrier air plasma jet is designed to inactivate bacteria in aqueous media in direct and indirect exposure modes of treatment. The resistive barrier plasma jet is designed to operate at both dc and standard 50-60 Hz low frequency ac power input and the ambient air at 50% humidity level was used as the operating gas. The voltage-current characteristics of the plasma jet were analyzed and the operating frequency of the discharge was measured to be 20 kHz and the plasma power was measured to be 26 W. The plasma jet rotational temperatures (Trot) are obtained from the optical emission spectra, from the N2C-B(2+) transitions by matching the experimental spectrum results with the Spectra Air (SPECAIR) simulation spectra. The reactive oxygen and nitrogen species were measured using optical emission spectroscopy and gas analyzers, for direct and indirect treatment modes. The nitric oxides (NO) were observed to be the predominant long lived reactive nitrogen species produced by the plasma. Three different bacteria including Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative), and Neisseria meningitidis (Gram-negative) were suspended in an aqueous media and treated by the resistive barrier air plasma jet in direct and indirect exposure modes. The results show that a near complete bacterial inactivation was achieved within 120 s for both direct and indirect plasma treatment of S. aureus and E. coli bacteria. Conversely, a partial inactivation of N. meningitidis was observed by 120 s direct plasma exposure and insignificant inactivation was observed for the indirect plasma exposure treatment. Plasma induced shifts in N. meningitidis gene expression was analyzed using pilC gene expression as a representative gene and the results showed a reduction in the expression of the pilC gene compared to untreated samples suggesting that the observed protection against NO may be regulated by other genes.

  9. Pulvinar inactivation disrupts selection of movement plans.

    PubMed

    Wilke, Melanie; Turchi, Janita; Smith, Katy; Mishkin, Mortimer; Leopold, David A

    2010-06-23

    The coordinated movement of the eyes and hands under visual guidance is an essential part of goal-directed behavior. Several cortical areas known to be involved in this process exchange projections with the dorsal aspect of the thalamic pulvinar nucleus, suggesting that this structure may play a central role in visuomotor behavior. Here, we used reversible inactivation to investigate the role of the dorsal pulvinar in the selection and execution of visually guided manual and saccadic eye movements in macaque monkeys. We found that unilateral pulvinar inactivation resulted in a spatial neglect syndrome accompanied by visuomotor deficits including optic ataxia during visually guided limb movements. Monkeys were severely disrupted in their visually guided behavior regarding space contralateral to the side of the injection in several domains, including the following: (1) target selection in both manual and oculomotor tasks, (2) limb usage in a manual retrieval task, and (3) spontaneous visual exploration. In addition, saccades into the ipsilesional field had abnormally short latencies and tended to overshoot their mark. None of the deficits could be explained by a visual field defect or primary motor deficit. These findings highlight the importance of the dorsal aspect of the pulvinar nucleus as a critical hub for spatial attention and selection of visually guided actions.

  10. IL26 gene inactivation in Equidae.

    PubMed

    Shakhsi-Niaei, M; Drögemüller, M; Jagannathan, V; Gerber, V; Leeb, T

    2013-12-01

    Interleukin-26 (IL26) is a member of the IL10 cytokine family. The IL26 gene is located between two other well-known cytokines genes of this family encoding interferon-gamma (IFNG) and IL22 in an evolutionary conserved gene cluster. In contrast to humans and most other mammals, mice lack a functional Il26 gene. We analyzed the genome sequences of other vertebrates for the presence or absence of functional IL26 orthologs and found that the IL26 gene has also become inactivated in several equid species. We detected a one-base pair frameshift deletion in exon 2 of the IL26 gene in the domestic horse (Equus caballus), Przewalski horse (Equus przewalskii) and donkey (Equus asinus). The remnant IL26 gene in the horse is still transcribed and gives rise to at least five alternative transcripts. None of these transcripts share a conserved open reading frame with the human IL26 gene. A comparative analysis across diverse vertebrates revealed that the IL26 gene has also independently been inactivated in a few other mammals, including the African elephant and the European hedgehog. The IL26 gene thus appears to be highly variable, and the conserved open reading frame has been lost several times during mammalian evolution.

  11. Photochemical inactivation of alpha- and poxviruses.

    PubMed

    Sagripanti, Jose-Luis; Marschall, Hans-Jürgen; Voss, Lucy; Hülseweh, Birgit

    2011-01-01

    The objective of this study was to determine whether photochemical inactivation of viruses could be accomplished with high efficiency while preserving the molecular integrity of viral targets allowing subsequent diagnostic tests to be performed at a lower level of containment and cost. We studied the effect of 5-iodonaphthyl 1-azide (INA) and amotosalen (AMO, also known as S-59), which are photochemicals known to target either viral proteins or nucleic acids, respectively. We found that vaccinia virus (VACV, an orthopox virus with a DNA genome) and pixuna virus (PIXV, an alphavirus with an RNA genome) were stable when irradiated with UVA alone or when exposed to either INA or AMO in the dark. AMO followed by UVA exposure was at least 1000-fold more virucidal than INA/UVA on vaccinia and pixuna viruses treated under similar conditions. Photoinactivation with either INA or AMO at conditions that abolished viral infectivity resulted in only minimal impairment of subsequent ELISA and PCR testing. The results presented in this study should assist in developing methods to inactivate in the field environmental and forensic samples suspected of viral contamination, thus limiting the need for costly security and safety operations after an accidental or intentional viral release.

  12. Virus inactivation in aluminum and polyaluminum coagulation.

    PubMed

    Matsui, Yoshihiko; Matsushita, Taku; Sakuma, Satoru; Gojo, Takahito; Mamiya, Teppei; Suzuoki, Hiroshi; Inoue, Takanobu

    2003-11-15

    Inorganic aluminum salts, such as aluminum sulfate, are coagulants that cause small particles, such as bacteria and viruses as well as inorganic particles, to destabilize and combine into larger aggregates. In this investigation, batch coagulation treatments of water samples spiked with Qbeta, MS2, T4, and P1 viruses were conducted with four different aluminum coagulants. The total infectious virus concentration in the suspension of floc particles that eventually formed by dosing with coagulant was measured after the floc particles were dissolved by raising the pH with an alkaline beef extract solution. The virus concentrations were extremely reduced after the water samples were dosed with aluminum coagulants. Viruses mixed with and adsorbed onto preformed aluminum hydroxide floc were, however, completely recovered after the floc dissolution. These results indicated that the aluminum coagulation process inactivates viruses. Virucidal activity was most prominent with the prehydrolyzed aluminum salt coagulant, polyaluminum chloride (PACl). Virucidal activity was lower in river water than in ultrapure water--natural organic matter in the river water depressed the virucidal activity. Mechanisms and kinetics of the virus inactivation were discussed. Our results suggest that intermediate polymers formed during hydrolysis of the aluminum coagulants sorbed strongly to viruses, either rendering them inactive or preventing infectivity.

  13. Titanium dioxide photocatalytic inactivation of prions.

    PubMed

    Paspaltsis, Ioannis; Kotta, Konstantia; Lagoudaki, Roza; Grigoriadis, Nikolaos; Poulios, Ioannis; Sklaviadis, Theodoros

    2006-10-01

    Prions are postulated to be the infectious agents of a family of transmissible, fatal, neurodegenerative disorders affecting both humans and animals. The possibility of prion transmission constitutes a public-health risk that confronts regulatory authorities everywhere. The main problem in handling prions is the fact that they are extremely resistant to standard decontamination methods. Thus, the use of harsh and expensive practices to destroy prions is inevitable. The development of applicable and efficient prion-inactivation practices is still highly important for the prevention of accidental transmission. In the search for effective and environmentally friendly methods to eliminate organic compounds and bacteria, much attention has been focused on the so-called advanced oxidation processes. These are based on the formation of hydroxyl radicals, which are known to possess a high reductive potential. This study tested the potential of titanium dioxide, an inexpensive and completely inert reagent, to inactivate prions in a heterogeneous photocatalytic process. Initial in vitro experiments were followed by a bioassay with the scrapie strain 263K in Syrian hamsters. The results obtained from this study indicate that titanium dioxide photocatalytic treatment of scrapie-infected brain homogenates reduces infectivity titres significantly.

  14. FEF inactivation with improved optogenetic methods.

    PubMed

    Acker, Leah; Pino, Erica N; Boyden, Edward S; Desimone, Robert

    2016-11-15

    Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools to a classic question in oculomotor control. First, we measured light absorption and heat propagation in vivo, optimized the conditions for using the red-light-shifted halorhodopsin Jaws in primates, and developed a large-volume illuminator to maximize light delivery with minimal heating and tissue displacement. Together, these advances allowed for nearly universal neuronal inactivation across more than 10 mm(3) of the cortex. Using these tools, we demonstrated large behavioral changes (i.e., up to several fold increases in error rate) with relatively low light power densities (≤100 mW/mm(2)) in the frontal eye field (FEF). Pharmacological inactivation studies have shown that the FEF is critical for executing saccades to remembered locations. FEF neurons increase their firing rate during the three epochs of the memory-guided saccade task: visual stimulus presentation, the delay interval, and motor preparation. It is unclear from earlier work, however, whether FEF activity during each epoch is necessary for memory-guided saccade execution. By harnessing the temporal specificity of optogenetics, we found that FEF contributes to memory-guided eye movements during every epoch of the memory-guided saccade task (the visual, delay, and motor periods).

  15. Photodynamic inactivation of pathogens causing infectious keratitis

    NASA Astrophysics Data System (ADS)

    Simon, Carole; Wolf, G.; Walther, M.; Winkler, K.; Finke, M.; Hüttenberger, D.; Bischoff, Markus; Seitz, B.; Cullum, J.; Foth, H.-J.

    2014-03-01

    The increasing prevalence of antibiotic resistance requires new approaches also for the treatment of infectious keratitis. Photodynamic Inactivation (PDI) using the photosensitizer (PS) Chlorin e6 (Ce6) was investigated as an alternative to antibiotic treatment. An in-vitro cornea model was established using porcine eyes. The uptake of Ce6 by bacteria and the diffusion of the PS in the individual layers of corneal tissue were investigated by fluorescence. After removal of the cornea's epithelium Ce6-concentrations < 1 mM were sufficient to reach a penetration depth of 500 μm. Liquid cultures of microorganisms were irradiated using a specially constructed illumination chamber made of Spectralon(R) (reflectance: 99 %), which was equipped with high power light emitting diodes (λ = 670 nm). Clinical isolates of Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) from keratitis patients were tested in liquid culture against different concentrations of Ce6 (1 - 512 μM) using 10 minutes irradiation (E = 18 J/cm2 ). This demonstrated that a complete inactivation of the pathogen strains were feasible whereby SA was slightly more susceptible than PA. 3909 mutants of the Keio collection of Escherichia coli (E.coli) were screened for potential resistance factors. The sensitive mutants can be grouped into three categories: transport mutants, mutants in lipopolysaccharide synthesis and mutants in the bacterial SOS-response. In conclusion PDI is seen as a promising therapy concept for infectious keratitis.

  16. X-changing information on X inactivation

    SciTech Connect

    Barakat, Tahsin Stefan; Jonkers, Iris; Monkhorst, Kim; Gribnau, Joost

    2010-03-10

    In female somatic cells of mammalian species one X chromosome is inactivated to ensure dosage equality of X-encoded genes between females and males, during development and adulthood. X chromosome inactivation (XCI) involves various epigenetic mechanisms, including RNA mediated gene silencing in cis, DNA methylation, and changes in chromatin modifications and composition. XCI therefore provides an attractive paradigm to study epigenetic gene regulation in a more general context. The XCI process starts with counting of the number of X chromosomes present in a nucleus, and initiation of XCI follows if this number exceeds one per diploid genome. Recently, X-encoded RNF12 has been identified as a dose-dependent activator of XCI. In addition, other factors, including the pluripotency factors OCT4, SOX2 and Nanog, have been implicated to play a role in suppression of initiation of XCI. In this review, we highlight and explain these new and old findings in the context of a stochastic model for X chromosome counting and XCI initiation.

  17. Inactivation of anthracyclines by serum heme proteins.

    PubMed

    Wagner, Brett A; Teesch, Lynn M; Buettner, Garry R; Britigan, Bradley E; Burns, C Patrick; Reszka, Krzysztof J

    2007-06-01

    We have previously shown that the anticancer agent doxorubicin undergoes oxidation and inactivation when exposed to myeloperoxidase-containing human leukemia HL-60 cells, or to isolated myeloperoxidase, in the presence of hydrogen peroxide and nitrite. In the current study we report that commercial fetal bovine serum (FBS) alone oxidizes doxorubicin in the presence of hydrogen peroxide and that nitrite accelerates this oxidation. The efficacy of inactivation was dependent on the concentration of serum present; no reaction was observed when hydrogen peroxide or serum was omitted. Peroxidase activity assays, based on oxidation of 3,3',5,5'-tetramethylbenzidine, confirmed the presence of a peroxidase in the sera from several suppliers. The peroxidative activity was contained in the >10000 MW fraction. We also found that hemoglobin, a heme protein likely to be present in commercial FBS, is capable of oxidizing doxorubicin in the presence of hydrogen peroxide and that nitrite further stimulates the reaction. In contrast to intact doxorubicin, the serum + hydrogen peroxide + nitrite treated drug appeared to be nontoxic for PC3 human prostate cancer cells. Together, this study shows that (pseudo)peroxidases present in sera catalyze oxidation of doxorubicin by hydrogen peroxide and that this diminishes the tumoricidal activity of the anthracycline, at least in in vitro settings. Finally, this study also points out that addition of H2O2 to media containing FBS will stimulate peroxidase-type of reactions, which may affect cytotoxic properties of studied compounds.

  18. Implications of the detailed fluctuation theorem for the sources of irreversibility in interfacial charge transfer processes.

    PubMed

    Bisquert, Juan

    2005-11-01

    We investigate from basic principles of nonequilibrium statistical mechanics the general reasons why electron transfer across an interface is associated with irreversible elements (resistances) in equivalent circuit modeling. We apply the detailed fluctuation theorem [C. Jarzynski, J. Stat. Phys. 98, 77 (2000)] to a simple model of an interface between two different materials. The elementary transition rates are interpreted in terms of the evolution of a microstate, and obey a ratio that is related to the heat absorbed from the phonon bath while promoting an electron to a higher energy level. The amount of irreversibility (the entropy production), and also the macroscopic current density, can be both obtained with the additional constraint that the system belongs in a particular mesostate, determined by the distribution of chemical and electrostatic potential.

  19. An Irreversible Inhibitor of HSP72 that Unexpectedly Targets Lysine-56.

    PubMed

    Pettinger, Jonathan; Le Bihan, Yann-Vaï; Widya, Marcella; van Montfort, Rob L M; Jones, Keith; Cheeseman, Matthew D

    2017-02-22

    The stress-inducible molecular chaperone, HSP72, is an important therapeutic target in oncology, but inhibiting this protein with small molecules has proven particularly challenging. Validating HSP72 inhibitors in cells is difficult owing to competition with the high affinity and abundance of its endogenous nucleotide substrates. We hypothesized this could be overcome using a cysteine-targeted irreversible inhibitor. Using rational design, we adapted a validated 8-N-benzyladenosine ligand for covalent bond formation and confirmed targeted irreversible inhibition. However, no cysteine in the protein was modified; instead, we demonstrate that lysine-56 is the key nucleophilic residue. Targeting this lysine could lead to a new design paradigm for HSP72 chemical probes and drugs.

  20. Biogenic methane, hydrogen escape, and the irreversible oxidation of early Earth.

    PubMed

    Catling, D C; Zahnle, K J; McKay, C

    2001-08-03

    The low O2 content of the Archean atmosphere implies that methane should have been present at levels approximately 10(2) to 10(3) parts per million volume (ppmv) (compared with 1.7 ppmv today) given a plausible biogenic source. CH4 is favored as the greenhouse gas that countered the lower luminosity of the early Sun. But abundant CH4 implies that hydrogen escapes to space (upward arrow space) orders of magnitude faster than today. Such reductant loss oxidizes the Earth. Photosynthesis splits water into O2 and H, and methanogenesis transfers the H into CH4. Hydrogen escape after CH4 photolysis, therefore, causes a net gain of oxygen [CO2 + 2H2O --> CH4 + 2O2 --> CO2 + O2 + 4H(upward arrow space)]. Expected irreversible oxidation (approximately 10(12) to 10(13) moles oxygen per year) may help explain how Earth's surface environment became irreversibly oxidized.

  1. Linear irreversible thermodynamics and Onsager reciprocity for information-driven engines.

    PubMed

    Yamamoto, Shumpei; Ito, Sosuke; Shiraishi, Naoto; Sagawa, Takahiro

    2016-11-01

    In the recent progress in nonequilibrium thermodynamics, information has been recognized as a kind of thermodynamic resource that can drive thermodynamic current without any direct energy injection. In this paper, we establish the framework of linear irreversible thermodynamics for a broad class of autonomous information processing. In particular, we prove that the Onsager reciprocity holds true with information: The linear response matrix is well-defined and is shown symmetric with both of the information affinity and the conventional thermodynamic affinity. As an application, we derive a universal bound for the efficiency at maximum power for information-driven engines in the linear regime. Our result reveals the fundamental role of information flow in linear irreversible thermodynamics.

  2. Self-adjoint Lyapunov variables, temporal ordering, and irreversible representations of Schroedinger evolution

    SciTech Connect

    Strauss, Y.

    2010-02-15

    In nonrelativistic quantum mechanics time enters as a parameter in the Schroedinger equation. However, there are various situations where the need arises to view time as a dynamical variable. In this paper we consider the dynamical role of time through the construction of a Lyapunov variable - i.e., a self-adjoint quantum observable whose expectation value varies monotonically as time increases. It is shown, in a constructive way, that a certain class of models admits a Lyapunov variable and that the existence of a Lyapunov variable implies the existence of a transformation mapping the original quantum mechanical problem to an equivalent irreversible representation. In addition, it is proven that in the irreversible representation there exists a natural time ordering observable splitting the Hilbert space at each t>0 into past and future subspaces.

  3. Entropy production in irreversible systems described by a Fokker-Planck equation.

    PubMed

    Tomé, Tânia; de Oliveira, Mário J

    2010-08-01

    We analyze the irreversibility and the entropy production in nonequilibrium interacting particle systems described by a Fokker-Planck equation by the use of a suitable master equation representation. The irreversible character is provided either by nonconservative forces or by the contact with heat baths at distinct temperatures. The expression for the entropy production is deduced from a general definition, which is related to the probability of a trajectory in phase space and its time reversal, that makes no reference a priori to the dissipated power. Our formalism is applied to calculate the heat conductance in a simple system consisting of two Brownian particles each one in contact to a heat reservoir. We show also the connection between the definition of entropy production rate and the Jarzynski equality.

  4. Nitric oxide inhibits irreversibly P815 cell proliferation: involvement of potassium channels.

    PubMed

    Costa, R S A; Assreuy, J

    2002-12-01

    Nitric oxide (NO) has been shown to inhibit both normal and cancer cell proliferation. Potassium channels are involved in cell proliferation and, as NO activates these channels, we investigated the effect of NO on the proliferation of murine mastocytoma cell lines and the putative involvement of potassium channels. NO (in the form of NO donors) caused dose-dependent inhibition of cell proliferation in the P815 cell line inducing growth arrest in the mitosis phase. Incubation with NO donor for 4 or 24 h had a similar inhibitory effect on cell proliferation, indicating that this effect is irreversible. The inhibitory effect of NO was completely prevented by the blockade of voltage- and calcium-dependent potassium channels, but not by blockade of ATP-dependent channels. NO inhibition of cell proliferation was unaffected by guanylate cyclase and by cytoskeleton disruptors. Therefore, NO inhibits cell proliferation irreversibly via a potassium channel-dependent but guanylate cyclase-independent pathway in murine mastocytoma cells.

  5. Irreversible processes without energy dissipation in an isolated Lipkin-Meshkov-Glick model.

    PubMed

    Puebla, Ricardo; Relaño, Armando

    2015-07-01

    For a certain class of isolated quantum systems, we report the existence of irreversible processes in which the energy is not dissipated. After a closed cycle in which the initial energy distribution is fully recovered, the expectation value of a symmetry-breaking observable changes from a value differing from zero in the initial state to zero in the final state. This entails the unavoidable loss of a certain amount of information and constitutes a source of irreversibility. We show that the von Neumann entropy of time-averaged equilibrium states increases in the same magnitude as a consequence of the process. We support this result by means of numerical calculations in an experimentally feasible system, the Lipkin-Meshkov-Glick model.

  6. On heat equation in the framework of classic irreversible thermodynamics with internal variables

    NASA Astrophysics Data System (ADS)

    Ciancio, Vincenzo; Restuccia, Liliana

    2016-06-01

    In this paper, we show that, using a procedure of classical irreversible thermodynamics (CIT) with internal variables, it is possible to describe the relaxation of thermal phenomena, obtaining some well known results of extended irreversible thermodynamics (EIT). In particular, we introduce as internal variables a vector and a second rank tensor, that influence the thermal transport phenomena, and we derive in the anisotropic and isotropic case, the phenomenological equations for these variables. In the case, in which the medium is isotropic, it is obtained that the total heat flux can be split in two parts: a first contribution J(0), governed by Fourier law, and a second contribution J(1), obeying Maxwell-Cattaneo-Vernotte (MCV) equation, in which a relaxation time is present. The obtained results may have applications in describing the thermal behavior in nanosystems (semiconductors, nanotubes,…), where the phenomena are fast and there are high-frequency thermal waves.

  7. Lagrangian formulation of irreversible thermodynamics and the second law of thermodynamics

    SciTech Connect

    Glavatskiy, K. S.

    2015-05-28

    We show that the equations which describe irreversible evolution of a system can be derived from a variational principle. We suggest a Lagrangian, which depends on the properties of the normal and the so-called “mirror-image” system. The Lagrangian is symmetric in time and therefore compatible with microscopic reversibility. The evolution equations in the normal and mirror-imaged systems are decoupled and describe therefore independent irreversible evolution of each of the systems. The second law of thermodynamics follows from a symmetry of the Lagrangian. Entropy increase in the normal system is balanced by the entropy decrease in the mirror-image system, such that there exists an “integral of evolution” which is a constant. The derivation relies on the property of local equilibrium, which states that the local relations between the thermodynamic quantities in non-equilibrium are the same as in equilibrium.

  8. Irreversible binding of o,p'-DDD in interrenal cells of Atlantic cod (Gadus morhua).

    PubMed

    Lindhe, Orjan; Brandt, Ingvar; Christiansen, Jørgen Schou; Ingebrigtsen, Kristian

    2003-03-01

    Precision-cut tissue slices of the anterior kidney from Atlantic cod (Gadus morhua) were prepared with a Krumdieck tissue slicer and exposed to 2-(2-chlorophenyl)-2-(4-chloro-(14C)phenyl)-1,1-dichlorethane (o,p(')-[14C]DDD) in vitro. Microautoradiography revealed irreversible o,p(')-DDD-derived binding confined to the glucocorticoid producing interrenal cells (adrenocortical analogues). This cell-selective binding was confirmed by means of autoradiography at different levels of resolution on Atlantic cod administered o,p(')-[14C]DDD intragastrically. The results provide evidence for a site-specific metabolic activation and irreversible binding of o,p(')-DDD in the interrenal cells, which, in turn, may modify glucocorticoid homeostasis.

  9. Intermode Coupling Drives the Irreversible Tautomerization in Porphycene on Copper(111) Induced by Scanning Tunnelling Microscopy.

    PubMed

    Novko, Dino; Blanco-Rey, María; Tremblay, Jean Christophe

    2017-03-02

    In this contribution, we develop a nonadiabatic theory that explains, from first-principles, the recently reported irreversible trans → cis tautomerization of porphycene on Cu(111) induced by a scanning tunnelling microscope at finite bias. The inelastic contribution to the STM current is found to excite a large number of skeletal vibrational modes of the molecule, thereby inducing a deformation of the potential energy landscape along the hydrogen transfer coordinate. Above a threshold bias, the stability of the tautomers is reversed, which indirectly drives the reaction via intermode coupling. The proposed potential deformation term accounts effectively for the excitation of all internal vibrational modes without increasing the dimensionality of the problem. The model yields information about reaction rates, explains the reaction irreversibility at low temperatures, and accounts for the presence of resonant processes.

  10. Simulation of lung tissue properties in age and irreversible obstructive syndromes using an aldehyde.

    PubMed Central

    Sugihara, T; Martin, C J

    1975-01-01

    Weak solutions of CHOH alter tissue properties, probably by forming intermolecular cross-linkages. The maximum length (Lmax) to which alveolar wall can be extended is reduced. If exposed to CHOH while extended, the resting length (LO) of alveolar wall increases. Maximum extensibility (Lambdamax equal to Lmax/LO) decreases. Similar changes are found in the alveolar wall of man with aging and are significantly more marked in patients with irreversible obstructive pulmonary syndromes. A reduction in the energy loss of the length-tension cycle (hysteresis) was seen after exposure to CHOH, however, that does not occur with age or in obstructive syndromes. Because an exposure of alveolar wall to elastase increases LO and hysteresis, we used a staged exposure to CHOH followed by elastase. Tissue suitably prepared by exposure to CHOH followed by elastolysis better simulates the tissue changes of age and irreversible obstructive syndromes. PMID:1141435

  11. Optimum criteria of an irreversible quantum Brayton refrigeration cycle with an ideal Bose gas

    NASA Astrophysics Data System (ADS)

    Wang, Hao; Liu, Sanqiu; He, Jizhou

    2008-11-01

    An irreversible cycle model of the quantum Brayton refrigeration cycle is established, in which finite-time processes and irreversibility in the two adiabatic processes are taken into account. On the basis of the thermodynamic properties of an ideal Bose gas, by using the optimal control-theory, the mathematical expressions for several important performance parameters, such as the coefficient of performance, power input and cooling load, are derived and some important performance parameters, e.g., the temperatures of the working substance at several important state-points, are optimized. By means of numerical predictions, the optimal performance characteristic curves of a Bose-Brayton refrigeration cycle are obtained and analyzed. Furthermore, some optimal operating regions including those for the cooling load, coefficient of performance and the temperatures of the cyclic working substance at the two important state-points are determined and evaluated. Finally, several special cases are discussed in detail.

  12. Linear irreversible thermodynamics and Onsager reciprocity for information-driven engines

    NASA Astrophysics Data System (ADS)

    Yamamoto, Shumpei; Ito, Sosuke; Shiraishi, Naoto; Sagawa, Takahiro

    2016-11-01

    In the recent progress in nonequilibrium thermodynamics, information has been recognized as a kind of thermodynamic resource that can drive thermodynamic current without any direct energy injection. In this paper, we establish the framework of linear irreversible thermodynamics for a broad class of autonomous information processing. In particular, we prove that the Onsager reciprocity holds true with information: The linear response matrix is well-defined and is shown symmetric with both of the information affinity and the conventional thermodynamic affinity. As an application, we derive a universal bound for the efficiency at maximum power for information-driven engines in the linear regime. Our result reveals the fundamental role of information flow in linear irreversible thermodynamics.

  13. Simulation of irreversible rock compaction effects on geopressured reservoir response: Topical report

    SciTech Connect

    Riney, T.D.

    1986-12-01

    A series of calculations are presented which quantitatively demonstrate the effects of nonlinear stress-deformation properties on the behavior of geopressured reservoirs. The range of stress-deformation parameters considered is based on information available from laboratory rock mechanics tests performed at the University of Texas at Austin and at Terra Tek, Inc. on cores recovered from geopressured wells. The effects of irreversible formation rock compaction, associated permeability reduction, and repetitive load/unload cycling are considered. The formation rock and geopressured brine properties are incorporated into an existing reservoir simulator using a bilinear model for the irreversible compaction process. Pressure drawdown and buildup testing of a well producing from the geopressured formation is simulated for a suite of calculations covering the range of formation parameters. The results are presented and discussed in terms of the inference (e.g., permeability and reservoir volume) that would be drawn from the simulated test data by an analyst using conventional methods.

  14. Irreversible electrical manipulation of magnetization on BiFeO{sub 3}-based heterostructures

    SciTech Connect

    Xu, Qingyu E-mail: jdu@nju.edu.cn; Xu, Zhenyu; He, Maocheng; Du, Jun E-mail: jdu@nju.edu.cn; Cao, Yanqiang

    2015-05-07

    We prepared several heterostructures, Co/Bi{sub 0.90}La{sub 0.10}FeO{sub 3} on surface oxidized Si or (111) SrTiO{sub 3} and NiFe/Bi{sub 0.90}La{sub 0.10}FeO{sub 3} on (001) SrTiO{sub 3} substrates using LaNiO{sub 3} as bottom electrode. With different strategies of voltage application, the exchange bias field H{sub E} decreased with increasing voltage irreversibly for all the heterostructures at room temperature. The chemical state at the NiFe/Bi{sub 0.90}La{sub 0.10}FeO{sub 3} interface was studied by X-ray photoelectron spectroscopy before and after the electrical manipulation. The oxidization of the metallic ferromagnetic layer at interface after the electrical manipulation has been confirmed, which might explain the irreversibility.

  15. Microbiome of Deep Dentinal Caries Lesions in Teeth with Symptomatic Irreversible Pulpitis

    PubMed Central

    Rôças, Isabela N.; Rachid, Caio T. C. C.; Lima, Kenio C.; Assunção, Isauremi V.; Gomes, Patrícia N.; Siqueira, José F.

    2016-01-01

    This study used a next-generation sequencing approach to identify the bacterial taxa occurring in the advanced front of caries biofilms associated with pulp exposure and irreversible pulpitis. Samples were taken from the deepest layer of dentinal caries lesions associated with pulp exposure in 10 teeth diagnosed with symptomatic irreversible pulpitis. DNA was extracted and the microbiome was characterized on the basis of the V4 hypervariable region of the 16S rRNA gene by using paired-end sequencing on Illumina MiSeq device. Bacterial taxa were mapped to 14 phyla and 101 genera composed by 706 different OTUs. Three phyla accounted for approximately 98% of the sequences: Firmicutes, Actinobacteria and Proteobacteria. These phyla were also the ones with most representatives at the species level. Firmicutes was the most abundant phylum in 9/10 samples. As for genera, Lactobacillus accounted for 42.3% of the sequences, followed by Olsenella (13.7%), Pseudoramibacter (10.7%) and Streptococcus (5.5%). Half of the samples were heavily dominated by Lactobacillus, while in the other half lactobacilli were in very low abundance and the most dominant genera were Pseudoramibacter, Olsenella, Streptococcus, and Stenotrophomonas. High bacterial diversity occurred in deep dentinal caries lesions associated with symptomatic irreversible pulpitis. The microbiome could be classified according to the relative abundance of Lactobacillus. Except for Lactobacillus species, most of the highly prevalent and abundant bacterial taxa identified in this study have been commonly detected in infected root canals. The detected taxa can be regarded as candidate pathogens for irreversible pulpitis and possibly the pioneers in pulp invasion to initiate endodontic infection. PMID:27135405

  16. Microbiome of Deep Dentinal Caries Lesions in Teeth with Symptomatic Irreversible Pulpitis.

    PubMed

    Rôças, Isabela N; Alves, Flávio R F; Rachid, Caio T C C; Lima, Kenio C; Assunção, Isauremi V; Gomes, Patrícia N; Siqueira, José F

    2016-01-01

    This study used a next-generation sequencing approach to identify the bacterial taxa occurring in the advanced front of caries biofilms associated with pulp exposure and irreversible pulpitis. Samples were taken from the deepest layer of dentinal caries lesions associated with pulp exposure in 10 teeth diagnosed with symptomatic irreversible pulpitis. DNA was extracted and the microbiome was characterized on the basis of the V4 hypervariable region of the 16S rRNA gene by using paired-end sequencing on Illumina MiSeq device. Bacterial taxa were mapped to 14 phyla and 101 genera composed by 706 different OTUs. Three phyla accounted for approximately 98% of the sequences: Firmicutes, Actinobacteria and Proteobacteria. These phyla were also the ones with most representatives at the species level. Firmicutes was the most abundant phylum in 9/10 samples. As for genera, Lactobacillus accounted for 42.3% of the sequences, followed by Olsenella (13.7%), Pseudoramibacter (10.7%) and Streptococcus (5.5%). Half of the samples were heavily dominated by Lactobacillus, while in the other half lactobacilli were in very low abundance and the most dominant genera were Pseudoramibacter, Olsenella, Streptococcus, and Stenotrophomonas. High bacterial diversity occurred in deep dentinal caries lesions associated with symptomatic irreversible pulpitis. The microbiome could be classified according to the relative abundance of Lactobacillus. Except for Lactobacillus species, most of the highly prevalent and abundant bacterial taxa identified in this study have been commonly detected in infected root canals. The detected taxa can be regarded as candidate pathogens for irreversible pulpitis and possibly the pioneers in pulp invasion to initiate endodontic infection.

  17. Dipeptide-derived nitriles containing additional electrophilic sites: potentially irreversible inhibitors of cysteine proteases.

    PubMed

    Löser, Reik; Gütschow, Michael

    2009-12-01

    Heterocyclic and open-chain dipeptide-derived nitriles have been synthesized, containing an additional electrophilic center enabling the subsequent covalent modification of the thioimidate nitrogen formed in situ at the active site of the enzyme. The inhibitory potential of these nitriles against the cysteine proteases papain and cathepsins L, S, and K was determined. The open-chain dipeptide nitriles 8 and 10 acted as moderate reversible inhibitors, but no evidence for an irreversible inhibition of these enzymes was discernable.

  18. Time irreversibility of the statistics of a single particle in compressible turbulence

    NASA Astrophysics Data System (ADS)

    Grafke, Tobias; Frishman, Anna; Falkovich, Gregory

    2015-04-01

    We investigate time irreversibility from the point of view of a single particle in Burgers turbulence. Inspired by the recent work for incompressible flows [Xu et al., Proc. Natl. Acad. Sci. USA 111, 7558 (2014), 10.1073/pnas.1321682111], we analyze the evolution of the kinetic energy for fluid markers and use the fluctuations of the instantaneous power as a measure of time irreversibility. For short times, starting from a uniform distribution of markers, we find the scaling <[E(t ) -E (0 ) ] n>∝t and ∝Ren -1 for the power as a function of the Reynolds number. Both observations can be explained using the "flight-crash" model, suggested by Xu et al. Furthermore, we use a simple model for shocks that reproduces the moments of the energy difference, including the pre-factor for . To complete the single-particle picture for Burgers we compute the moments of the Lagrangian velocity difference and show that they are bifractal. This arises in a similar manner to the bifractality of Eulerian velocity differences. In the above setting, time irreversibility is directly manifest as particles eventually end up in shocks. We additionally investigate time irreversibility in the long-time limit when all particles are located inside shocks and the Lagrangian velocity statistics are stationary. We find the same scalings for the power and energy differences as at short times and argue that this is also a consequence of rare "flight-crash" events related to shock collisions.

  19. Irreversible Catalyst Activation Enables Hyperpolarization and Water Solubility for NMR Signal Amplification by Reversible Exchange

    DTIC Science & Technology

    2016-09-12

    Irreversible Catalyst Activation Enables Hyperpolarization and Water Solubility for NMR Signal Amplification by Reversible Exchange Milton L. Truong...Supporting Information ABSTRACT: Activation of a catalyst [IrCl(COD)(IMes)] (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene; COD = cyclooctadiene...for signal amplification by reversible exchange (SABRE) was monitored by in situ hyperpolarized proton NMR at 9.4 T. During the catalyst -activation

  20. Microstructural evolution and irreversibility in the viscoelastic response of mesoscopic dusty-plasma liquids.

    PubMed

    Chan, Chia-Ling; I, Lin

    2007-03-09

    We experimentally demonstrate the viscoelastic response and construct a microscopic dynamical picture using a quasi-2D dusty-plasma liquid confined in a mesoscopic gap and sheared periodically. The correlation between microdisplacement and structural evolution at the discrete kinetic level is explored. Through hopping, the structural rearrangement associated with shear enhanced stretching, kinking, breaking, and reconnection of local lattice lines generates irreversible plastic deformation. The strain energy accumulation in the twisted regions without topological rearrangement is the source for local rebound.

  1. Hydrophilic fraction of natural organic matter causing irreversible fouling of microfiltration and ultrafiltration membranes.

    PubMed

    Yamamura, Hiroshi; Okimoto, Kenji; Kimura, Katsuki; Watanabe, Yoshimasa

    2014-05-01

    Although membrane filtration is a promising technology in the field of drinking water treatment, persistent membrane fouling remains a major disadvantage. For more efficient operation, causative agents of membrane fouling need to be identified. Membrane fouling can be classified into physically reversible and irreversible fouling on basis of the removability of the foulants by physical cleaning. Four types of natural organic matter (NOM) in river water used as a source of drinking water were fractionated into hydrophobic and hydrophilic fractions, and their potential to develop irreversible membrane fouling was evaluated by a bench-scale filtration experiment together with spectroscopic and chromatographic analyses. In this study, only dissolved NOM was investigated without consideration of interactions of NOM fractions with particulate matter. Results demonstrated that despite identical total organic carbon (TOC), fouling development trends were significantly different between hydrophilic and hydrophobic fractions. The hydrophobic fractions did not increase membrane resistance, while the hydrophilic fractions caused severe loss of membrane permeability. These results were identical with the case when the calcium was added to hydrophobic and hydrophilic fractions. The largest difference in NOM characteristics between hydrophobic and hydrophilic fractions was the presence or absence of macromolecules; the primary constituent causing irreversible fouling was inferred to be "biopolymers", including carbohydrates and proteins. In addition, the results demonstrated that the extent of irreversible fouling was considerably different depending on the combination of membrane materials and NOM characteristics. Despite identical nominal pore size (0.1 μm), a polyvinylidene fluoride (PVDF) membrane was found to be more rapidly fouled than a PE membrane. This is probably explained by the generation of strong hydrogen bonding between hydroxyl groups of biopolymers and fluorine

  2. Irreversible modification of magnetic properties of Pt/Co/Pt ultrathin films by femtosecond laser pulses

    SciTech Connect

    Kisielewski, J.; Dobrogowski, W.; Kurant, Z.; Stupakiewicz, A.; Tekielak, M.; Maziewski, A.; Kirilyuk, A.; Kimel, A.; Rasing, Th.; Baczewski, L. T.; Wawro, A.

    2014-02-07

    Annealing ultrathin Pt/Co/Pt films with single femtosecond laser pulses leads to irreversible spin-reorientation transitions and an amplification of the magneto-optical Kerr rotation. The effect was studied as a function of the Co thickness and the pulse fluence, revealing two-dimensional diagrams of magnetic properties. While increasing the fluence, the creation of two branches of the out-of-plane magnetization state was found.

  3. Estimating Temperature Rise Due to Flashlamp Heating Using Irreversible Temperature Indicators

    NASA Technical Reports Server (NTRS)

    Koshti, Ajay M.

    1999-01-01

    One of the nondestructive thermography inspection techniques uses photographic flashlamps. The flashlamps provide a short duration (about 0.005 sec) heat pulse. The short burst of energy results in a momentary rise in the surface temperature of the part. The temperature rise may be detrimental to the top layer of the part being exposed. Therefore, it is necessary to ensure the nondestructive nature of the technique. Amount of the temperature rise determines whether the flashlamp heating would be detrimental to the part. A direct method for the temperature measurement is to use of an infrared pyrometer that has much shorter response time than the flash duration. In this paper, an alternative technique is given using the irreversible temperature 'indicators. This is an indirect technique and it measures the temperature rise on the irreversible temperature indicators and computes the incident heat flux. Once the heat flux is known, the temperature rise on the part can be computed. A wedge shaped irreversible temperature indicator for measuring the heat flux is proposed. A procedure is given to use the wedge indicator.

  4. Understanding Irreversible Degradation of Nb3Sn Wires with Fundamental Fracture Mechanics

    SciTech Connect

    Zhai, Yuhu; Calzolaio, Ciro; Senatore, Carmine

    2014-08-01

    Irreversible performance degradation of advanced Nb3Sn superconducting wires subjected to transverse or axial mechanical loading is a critical issue for the design of large-scale fusion and accelerator magnets such as ITER and LHC. Recent SULTAN tests indicate that most cable-in-conduit conductors for ITER coils made of Nb3Sn wires processed by various fabrication techniques show similar performance degradation under cyclic loading. The irreversible degradation due to filament fracture and local strain accumulation in Nb3Sn wires cannot be described by the existing strand scaling law. Fracture mechanic modeling combined with X-ray diffraction imaging of filament micro-crack formation inside the wires under mechanical loading may reveal exciting insights to the wire degradation mechanisms. We apply fundamental fracture mechanics with a singularity approach to study influence of wire filament microstructure of initial void size and distribution to local stress concentration and potential crack propagation. We report impact of the scale and density of the void structure on stress concentration in the composite wire materials for crack initiation. These initial defects result in an irreversible degradation of the critical current beyond certain applied stress. We also discuss options to minimize stress concentration in the design of the material microstructure for enhanced wire performance for future applications.

  5. Anesthetic efficacy of lidocaine/meperidine for inferior alveolar nerve blocks in patients with irreversible pulpitis.

    PubMed

    Bigby, Jason; Reader, Al; Nusstein, John; Beck, Mike

    2007-01-01

    The purpose of this prospective, randomized, single-blind study was to compare the anesthetic efficacy of lidocaine with epinephrine to lidocaine plus meperidine with epinephrine for inferior alveolar nerve blocks (IAN) in patients with mandibular posterior teeth experiencing irreversible pulpitis. Forty-eight emergency patients diagnosed with irreversible pulpitis of a mandibular posterior tooth randomly received, in a single-blind manner, 36 mg of lidocaine with 18 mug epinephrine or 36 mg of lidocaine with 18 mug of epinephrine plus 36 mg meperidine with 18 mug epinephrine, using a conventional inferior alveolar nerve block. Endodontic access was begun 15 minutes after solution deposition, and all patients were required to have profound lip numbness. Success was defined as no or mild pain (visual analog scale recordings) upon endodontic access or initial instrumentation. The success rate for the inferior alveolar nerve block using the lidocaine solution was 26%, and for the lidocaine/meperidine solution, the success rate was 12%. There was no significant difference (p = 0.28) between the two solutions. In conclusion, for mandibular posterior teeth with irreversible pulpitis, the addition of 36 mg of meperidine to a lidocaine solution administered in a conventional IAN block did not improve the success rate over a standard lidocaine solution.

  6. Nonlinear Gamow vectors, shock waves, and irreversibility in optically nonlocal media

    NASA Astrophysics Data System (ADS)

    Gentilini, Silvia; Braidotti, Maria Chiara; Marcucci, Giulia; DelRe, Eugenio; Conti, Claudio

    2015-08-01

    Dispersive shock waves dominate wave-breaking phenomena in Hamiltonian systems. In the absence of loss, these highly irregular and disordered waves are potentially reversible. However, no experimental evidence has been given about the possibility of inverting the dynamics of a dispersive shock wave and turn it into a regular wavefront. Nevertheless, the opposite scenario, i.e., a smooth wave generating turbulent dynamics, is well studied and observed in experiments. Here we introduce a theoretical formulation for the dynamics in a highly nonlocal and defocusing medium described by the nonlinear Schroedinger equation. Our theory unveils a mechanism that enhances the degree of irreversibility. This mechanism explains why a dispersive shock cannot be reversed in evolution even for an arbitrarily small amount of loss. Our theory is based on the concept of nonlinear Gamow vectors, i.e., power-dependent generalizations of the counterintuitive and hereto-elusive exponentially decaying states in Hamiltonian systems. We theoretically show that nonlinear Gamow vectors play a fundamental role in nonlinear Schroedinger models: They may be used as a generalized basis for describing the dynamics of the shock waves and affect the degree of irreversibility of wave-breaking phenomena. Gamow vectors allow analytical calculation of the amount of breaking of time reversal with a quantitative agreement with numerical solutions. We also show that a nonlocal, nonlinear optical medium may act as a simulator for the experimental investigation of quantum irreversible models, as the reversed harmonic oscillator.

  7. Calcitonin gene-related peptide receptor expression in alternatively activated monocytes/macrophages during irreversible pulpitis.

    PubMed

    Caviedes-Bucheli, Javier; Moreno, Gloria Cristina; López, María Paula; Bermeo-Noguera, Ana Milena; Pacheco-Rodríguez, Gloriana; Cuellar, Adriana; Muñoz, Hugo Roberto

    2008-08-01

    The purpose of this study was to quantify the percentage and the mean fluorescence intensity of viable alternatively activated monocytes/macrophages (AAMø) CD163+ positive for calcitonin gene-related peptide receptor (CGRPr) within the total AAMø population in human dental pulp. Pulp tissue samples were collected from teeth with a clinical diagnosis of irreversible pulpitis (n = 13), pulps with induced inflammation (n = 13), and normal pulps (n = 13). All samples were labeled to identify positive cells for CGRPr and CD163 using a flow cytometry assay. Results demonstrated that a high percentage of total viable AAMø CD163+ expressed CGRPr on their membranes (72.12% in healthy pulp, 62.20% in irreversible pulpitis, and 58.01% in induced pulpitis). Significant differences were found between mean AAMø CD163+ fluorescence for CGRPr according to pulp condition, being greater in irreversible pulpitis. It can be concluded that AAMø CD163+ are expressed during normal and inflammatory processes, supporting the hypothesis that they could exercise an anti-inflammatory action that could be controlled by CGRP signaling after its binding.

  8. Calcium-Enriched Mixture Pulpotomy of Primary Molar Teeth with Irreversible Pulpitis. A Clinical Study

    PubMed Central

    Memarpour, Mahtab; Fijan, Soleiman; Asgary, Saeed; Keikhaee, Marzieh

    2016-01-01

    Objectives: To evaluate the outcome of vital pulp therapy in primary teeth with irreversible pulpitis by using calcium-enriched mixture (CEM) cement according to clinical and radiographic assessment. Participants and Methods: Fifty primary molar teeth with irreversible pulpitis in 50 children aged 6-8 years underwent pulpotomy using CEM cement as the dressing material. Following pulpotomy, pain intensity was evaluated by use of a visual analog scale at 1 and 7 days from the treatment and in clinical appointments at 3, 6 and 12 months after baseline. Radiographic evaluation was performed at 6 and 12 months. Data were analyzed using the McNemar test. Results: A total of 42 children (mean age 7.26 ± 0.82 year) completed the study. After one day treatment 56 % of children reported complete relief of pain and after 7 days 62% reported the same. However, two children complained of increased pain 1 day after treatment. None of the children reported pain in the subsequent appointments. One child complained of tenderness in percussion after 6 months. Pulp canal obliteration was the most common change in the radiographic assessment. There was no significant difference between clinical (92.8%) and radiographic (90.4%) success (p=0.990). Conclusion: Pulpotomy using CEM cement could present a successful treatment in primary molar teeth with irreversible pulpitis. PMID:27326265

  9. Extended irreversible thermodynamics modeling for self-heating and dissipation in piezoelectric ceramics.

    PubMed

    Lu, Xia; Hanagud, Sathya V

    2004-12-01

    Self-heating or dissipation of piezoelectric ceramic elements is observed to be severe under dynamic operations even in the linear range. In this paper, a nonequilibrium thermodynamic model is developed to delineate the coupled irreversible mechanical, electric, and thermal processes, which jointly contribute to dissipation. Specifically, additional nonequilibrium state variables, also known as thermodynamic fluxes, are brought in to describe each of these processes. The characteristic relaxation of these processes is modeled. The nonnegative rate of entropy production is found to be in quadratic form of thermodynamics fluxes. The energy balance equation, which governs the transformation between different energy forms, is obtained in the framework of extended irreversible thermodynamics. Using this model, the dissipation of a piezoceramic stack actuator under harmonic electric or mechanical loadings in linear operation range is studied. The harmonic-balance methods are utilized as solution techniques. In contrast to the existing piezoelectric dissipation models, the dissipation by the developed model is verified to nonlinearly depend on operating frequency, with a peak dissipation occurring at some operating frequency that is related to characteristic relaxation of irreversible processes. The measurements of newly introduced parameters are also discussed.

  10. Effect of uniaxial stress on the reversible and irreversible permeabilities of 2% Mn pipeline steel

    SciTech Connect

    Makar, J.M.; Atherton, D.L. . Dept. of Physics)

    1994-07-01

    The results of a study of the effects of constant uniaxial stress on the irreversible and reversible differential permeabilities of minor and saturation major hysteresis loops are presented, extending an earlier study which studied those permeability components on the initial magnetization curve. Tension was found to increase both the reversible and irreversible components of the saturation major loop differential permeability in the low magnetization region, and to decrease them in the high magnetization region. The opposite effect was found for compression. This effect was explained as the result of changes in the domain structure of the sample when stressed and a resulting change in the ratio of 90[degree] of 180[degree] domain walls. The differences between the upper and lower branches of the saturation major hysteresis loop reversible relative differential permeability were found to increase in tension and decrease in compression, with more complicated behavior occurring in the irreversible component. Minor loop behavior was also found to vary depending on the magnetization of the sample. In the low magnetization region tension was found to produce higher values and larger variations in both components of the relative differential permeability than the unstressed case, while compression produced lower values and smaller variations. The opposite behavior was found to be true in the high magnetization region, while an intermediate behavior with little or no change in both the relative differential permeability components was found to exist between the two extreme cases.

  11. Novel Selective and Irreversible Mosquito Acetylcholinesterase Inhibitors for Controlling Malaria and Other Mosquito-Borne Diseases

    NASA Astrophysics Data System (ADS)

    Dou, Dengfeng; Park, Jewn Giew; Rana, Sandeep; Madden, Benjamin J.; Jiang, Haobo; Pang, Yuan-Ping

    2013-01-01

    We reported previously that insect acetylcholinesterases (AChEs) could be selectively and irreversibly inhibited by methanethiosulfonates presumably through conjugation to an insect-specific cysteine in these enzymes. However, no direct proof for the conjugation has been published to date, and doubts remain about whether such cysteine-targeting inhibitors have desirable kinetic properties for insecticide use. Here we report mass spectrometric proof of the conjugation and new chemicals that irreversibly inhibited African malaria mosquito AChE with bimolecular inhibition rate constants (kinact/KI) of 3,604-458,597 M-1sec-1 but spared human AChE. In comparison, the insecticide paraoxon irreversibly inhibited mosquito and human AChEs with kinact/KI values of 1,915 and 1,507 M-1sec-1, respectively, under the same assay conditions. These results further support our hypothesis that the insect-specific AChE cysteine is a unique and unexplored target to develop new insecticides with reduced insecticide resistance and low toxicity to mammals, fish, and birds for the control of mosquito-borne diseases.

  12. Evidence for Irreversible Inhibition of Glycogen Synthase Kinase-3β by Tideglusib*

    PubMed Central

    Domínguez, Juan Manuel; Fuertes, Ana; Orozco, Leyre; del Monte-Millán, María; Delgado, Elena; Medina, Miguel

    2012-01-01

    Tideglusib is a GSK-3 inhibitor currently in phase II clinical trials for the treatment of Alzheimer disease and progressive supranuclear palsy. Sustained oral administration of the compound to a variety of animal models decreases Tau hyperphosphorylation, lowers brain amyloid plaque load, improves learning and memory, and prevents neuronal loss. We report here that tideglusib inhibits GSK-3β irreversibly, as demonstrated by the lack of recovery in enzyme function after the unbound drug has been removed from the reaction medium and the fact that its dissociation rate constant is non-significantly different from zero. Such irreversibility may explain the non-competitive inhibition pattern with respect to ATP shown by tideglusib and perhaps other structurally related compounds. The replacement of Cys-199 by an Ala residue in the enzyme seems to increase the dissociation rate, although the drug retains its inhibitory activity with decreased potency and long residence time. In addition, tideglusib failed to inhibit a series of kinases that contain a Cys homologous to Cys-199 in their active site, suggesting that its inhibition of GSK-3β obeys to a specific mechanism and is not a consequence of nonspecific reactivity. Results obtained with [35S]tideglusib do not support unequivocally the existence of a covalent bond between the drug and GSK-3β. The irreversibility of the inhibition and the very low protein turnover rate observed for the enzyme are particularly relevant from a pharmacological perspective and could have significant implications on its therapeutic potential. PMID:22102280

  13. Selection and constraint underlie irreversibility of tooth loss in cypriniform fishes

    PubMed Central

    Aigler, Sharon R.; Jandzik, David; Hatta, Kohei; Uesugi, Kentaro; Stock, David W.

    2014-01-01

    The apparent irreversibility of the loss of complex traits in evolution (Dollo’s Law) has been explained either by constraints on generating the lost traits or the complexity of selection required for their return. Distinguishing between these explanations is challenging, however, and little is known about the specific nature of potential constraints. We investigated the mechanisms underlying the irreversibility of trait loss using reduction of dentition in cypriniform fishes, a lineage that includes the zebrafish (Danio rerio) as a model. Teeth were lost from the mouth and upper pharynx in this group at least 50 million y ago and retained only in the lower pharynx. We identified regional loss of expression of the Ectodysplasin (Eda) signaling ligand as a likely cause of dentition reduction. In addition, we found that overexpression of this gene in the zebrafish is sufficient to restore teeth to the upper pharynx but not to the mouth. Because both regions are competent to respond to Eda signaling with transcriptional output, the likely constraint on the reappearance of oral teeth is the alteration of multiple genetic pathways required for tooth development. The upper pharyngeal teeth are fully formed, but do not exhibit the ancestral relationship to other pharyngeal structures, suggesting that they would not be favored by selection. Our results illustrate an underlying commonality between constraint and selection as explanations for the irreversibility of trait loss; multiple genetic changes would be required to restore teeth themselves to the oral region and optimally functioning ones to the upper pharynx. PMID:24821783

  14. Ultraviolet-induced irreversible tensile actuation of diacetylene/nylon microfibers

    NASA Astrophysics Data System (ADS)

    Chun, Kyoung-Yong; Choi, Changsoon; Baughman, Ray H.; Kim, Seon Jeong

    2016-07-01

    Photomechanically irreversible tensile-actuated diacetylene-embedding nylon 6/6 microfibers were investigated. 10,12-pentacosadiynoic acid (PCDA) monomer, which have conventionally provided a visual color change by temperature and photo-driven stimuli, was embedded in nylon 6/6 microfibers by wet spinning. By ultraviolet (UV) (254 nm) exposure, we observed irreversible tensile actuation (contraction) of linear (untwisted) and helical (twisted) structural microfibers. The tensile contraction of twisted nylon 6/6-PCDA microfiber containing10 mM PCDA was reached to ˜2% at 60 °C. Such irreversible tensile contraction can be promoted by volume contraction of PCDA monomers during UV exposure along with irregular structural deformation containing gauche conformation with increasing temperature. The kinetics of tensile contraction with temperature and time were shown by the Arrhenius plots. The activation energies were 34.3-35.7 kJ mol-1 as increasing the concentration of PCDA, implies that the nylon 6/6-PCDA microfibers could be applied to show time-temperature integrated device.

  15. Non-Equilibrium Thermodynamic Analysis on the Performance of AN Irreversible Thermally Driven Brownian Motor

    NASA Astrophysics Data System (ADS)

    Gao, Tianfu; Chen, Jincan

    Based on the general model of thermally-driven Brownian motors, an equivalent cycle system is established and the Onsager coefficients and efficiency at the maximum power output of the system are analytically calculated from non-equilibrium thermodynamics. It is found that the Onsager reciprocity relation holds and the Onsager coefficients are affected by the main irreversibilities existing in practical systems. Only when the heat leak and the kinetic energy change of the particle in the system are negligible, can the determinant of the Onsager matrix vanish. It is also found that in the frame of non-equilibrium thermodynamics, the power output and efficiency of an irreversible Brownian motor can be expressed to be the same form as those of an irreversible Carnot heat engine, so the results obtained here are of general significance. Moreover, these results are used to analyze the performance characteristics of a class of thermally-driven Brownian motors so that some important conclusions in literature may be directly derived from the present paper.

  16. Parametric optimization of an irreversible magnetic Ericsson refrigerator with finite heat reservoirs

    NASA Astrophysics Data System (ADS)

    Ye, X. M.; Lin, G. X.; Chen, J. C.; Brück, E.

    2007-04-01

    An irreversible cycle model of magnetic Ericsson refrigerators is established, in which the finite heat capacities of external heat reservoirs, heat-transfer irreversibility, inherent regenerative losses, additional regenerative losses due to thermal resistances and irreversibility inside the magnetic working substances are taken into account. On the basis of the thermodynamic equations of paramagnetic materials, the performance characteristics of the magnetic Ericsson refrigeration cycle are investigated. By using the method of the optimal control theory, the optimal equations between the cooling load and the coefficient of performance and between the cooling load and the power input are derived. Furthermore, the maximum cooling load and the corresponding coefficient of performance, the minimum power input and the optimally operating temperatures of the cyclic working substance are obtained. The optimal operating region of the magnetic Ericsson refrigerator is determined. The results obtained here are closer to the performance characteristics of practical magnetic refrigerators with finite heat reservoirs than those in literature and are helpful to the optimal design and performance improvement of magnetic Ericsson refrigerators.

  17. Irreversibility behavior in Ag-sheathed Bi-based superconducting wires

    SciTech Connect

    Dou, S.X.; Liu, H.K.; Guo, Y.C.; Wang, J.; Jin, X.J.; Hu, Q.Y. ); Shi, D.L.; Salem-Sugui, S.; Wang, Z. )

    1992-04-01

    Irreversibility lines for Ag/(Bi,Pb){sub 2}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub y}(2223) wires prepared through a phase formation- decomposition-recovery (PFDR) process and normal annealing process were determined using both AC susceptibility measurements under DC fields and magnetisation measurements. It was found that flux pinning was enhanced in the PFDR processed samples over the normal processed samples, in particular at temperature above 77 K. The PFDR process results in high mass density, grain alignment, uniform distribution of impurity precipitates and high density of defects. The irreversibility temperatures scaled with the applied field according to H{sup 1/3}, which is in contrast to H{sup 2/3} law for YBa{sub 2}Cu{sub 3}O{sub 7-x} and conventional superconductors. The irreversibility lines for PFDR processed tapes showed a crossover with those for normal processed tapes at temperature below {Tc} of the (Bi,Pb){sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+x} (2212), suggesting that at temperature above {Tc} of the 2212 phase, the 2212 as nonsuperconducting region, may serve as effective pinning sites for fluxoids.

  18. Alcohols produce reversible and irreversible acceleration of phospholipid flip-flop in the human erythrocyte membrane.

    PubMed

    Schwichtenhövel, C; Deuticke, B; Haest, C W

    1992-10-19

    The slow, non-mediated transmembrane movement of the lipid probes lysophosphatidylcholine, NBD-phosphatidylcholine and NBD-phosphatidylserine in human erythrocytes becomes highly enhanced in the presence of 1-alkanols (C2-C8) and 1,2-alkane diols (C4-C8). Above a threshold concentration characteristic for each alcohol, flip rates increase exponentially with the alcohol concentration. The equieffective concentrations of the alcohols decrease about 3-fold per methylene added. All 1-alkanols studied are equieffective at comparable calculated membrane concentrations. This is also observed or the 1,2-alkane diols, albeit at a 5-fold lower membrane concentration. At low alcohol concentrations, flip enhancement is reversible to a major extent upon removal of the alcohol. In contrast, a residual irreversible flip acceleration is observed following removal of the alcohol after a treatment at higher concentrations. The threshold concentrations to produce irreversible flip acceleration by 1-alkanols and 1,2-alkane diols are 1.5- and 3-fold higher than those for flip acceleration in the presence of the corresponding alcohols. A causal role in reversible flip-acceleration of a global increase of membrane fluidity or membrane polarity seems to be unlikely. Alcohols may act by increasing the probability of formation of transient structural defects in the hydrophobic barrier that already occur in the native membrane. Membrane defects responsible for irreversible flip-acceleration may result from alterations of membrane skeletal proteins by alcohols.

  19. Partially coherent ultrafast spectrography

    PubMed Central

    Bourassin-Bouchet, C.; Couprie, M.-E.

    2015-01-01

    Modern ultrafast metrology relies on the postulate that the pulse to be measured is fully coherent, that is, that it can be completely described by its spectrum and spectral phase. However, synthesizing fully coherent pulses is not always possible in practice, especially in the domain of emerging ultrashort X-ray sources where temporal metrology is strongly needed. Here we demonstrate how frequency-resolved optical gating (FROG), the first and one of the most widespread techniques for pulse characterization, can be adapted to measure partially coherent pulses even down to the attosecond timescale. No modification of experimental apparatuses is required; only the processing of the measurement changes. To do so, we take our inspiration from other branches of physics where partial coherence is routinely dealt with, such as quantum optics and coherent diffractive imaging. This will have important and immediate applications, such as enabling the measurement of X-ray free-electron laser pulses despite timing jitter. PMID:25744080

  20. Laparoscopic partial splenic resection.

    PubMed

    Uranüs, S; Pfeifer, J; Schauer, C; Kronberger, L; Rabl, H; Ranftl, G; Hauser, H; Bahadori, K

    1995-04-01

    Twenty domestic pigs with an average weight of 30 kg were subjected to laparoscopic partial splenic resection with the aim of determining the feasibility, reliability, and safety of this procedure. Unlike the human spleen, the pig spleen is perpendicular to the body's long axis, and it is long and slender. The parenchyma was severed through the middle third, where the organ is thickest. An 18-mm trocar with a 60-mm Endopath linear cutter was used for the resection. The tissue was removed with a 33-mm trocar. The operation was successfully concluded in all animals. No capsule tears occurred as a result of applying the stapler. Optimal hemostasis was achieved on the resected edges in all animals. Although these findings cannot be extended to human surgery without reservations, we suggest that diagnostic partial resection and minor cyst resections are ideal initial indications for this minimally invasive approach.