Determination of Titratable Acidity in Wine Using Potentiometric, Conductometric, and Photometric Methods

ERIC Educational Resources Information Center

Volmer, Dietrich A.; Curbani, Luana; Parker, Timothy A.; Garcia, Jennifer; Schultz, Linda D.; Borges, Endler Marcel

2017-01-01

This experiment describes a simple protocol for teaching acid-base titrations using potentiometry, conductivity, and/or photometry to determine end points without an added indicator. The chosen example examines the titratable acidity of a red wine with NaOH. Wines contain anthocyanins, the colors of which change with pH. Importantly, at the…

Spasmodic dysphonia: a seven-year audit of dose titration and demographics in the Indian population.

PubMed

Nerurkar, N K; Banu, T P

2014-07-01

This study aimed to evaluate the demographics of spasmodic dysphonia in the Indian population and to analyse the optimum dose titration of botulinum toxin type A in this group. A comparative analysis with international studies was also performed. The study involved a retrospective analysis and audit of botulinum toxin type A dose titration in spasmodic dysphonia patients who visited our voice clinic between January 2005 and January 2012. The average total therapeutic dose required for patients with adductor spasmodic dysphonia was 4.2 U per patient per vocal fold (total 8.4 U per patient), and for patients with abductor spasmodic dysphonia, it was 4.6 U per patient. Our audit revealed that 80 per cent of the spasmodic dysphonia patients were male, which contrasts dramatically with international studies, wherein around 80 per cent of spasmodic dysphonia patients were female. Our study also revealed a higher dose titration of botulinum toxin for the Indian spasmodic dysphonia population in both adductor and abductor spasmodic dysphonia cases.

Tested Demonstrations: Buffer Capacity of Various Acetic Acid-Sodium Acetate Systems: A Lecture Experiment.

ERIC Educational Resources Information Center

Donahue, Craig J.; Panek, Mary G.

1985-01-01

Background information and procedures are provided for a lecture experiment which uses indicators to illustrate the concept of differing buffer capacities by titrating acetic acid/sodium acetate buffers with 1.0 molar hydrochloric acid and 1.0 molar sodium hydroxide. A table with data used to plot the titration curve is included. (JN)

Using Conductivity Measurements to Determine the Identities and Concentrations of Unknown Acids: An Inquiry Laboratory Experiment

ERIC Educational Resources Information Center

Smith, K. Christopher; Garza, Ariana

2015-01-01

This paper describes a student designed experiment using titrations involving conductivity measurements to identify unknown acids as being either HCl or H[subscript 2]SO[subscript 4], and to determine the concentrations of the acids, thereby improving the utility of standard acid-base titrations. Using an inquiry context, students gain experience…

Titration of a Solid Acid Monitored by X-Ray Diffraction

ERIC Educational Resources Information Center

Dungey, Keenan E.; Epstein, Paul

2007-01-01

An experiment is described to introduce students to an important class of solid-state reactions while reinforcing concepts of titration by using a pH meter and a powder X-ray diffractometer. The experiment was successful in teaching students the abstract concepts of solid-state structure and diffraction by applying the diffraction concepts learned…

Volumetric Titrations Using Electrolytically Generated Reagents for the Determination of Ascorbic Acid and Iron in Dietary Supplement Tablets: An Undergraduate Laboratory Experiment

ERIC Educational Resources Information Center

Scanlon, Christopher; Gebeyehu, Zewdu; Griffin, Kameron; Dabke, Rajeev B.

2014-01-01

An undergraduate laboratory experiment for the volumetric quantitative analysis of ascorbic acid and iron in dietary supplement tablets is presented. Powdered samples of the dietary supplement tablets were volumetrically titrated against electrolytically generated reagents, and the mass of dietary reagent in the tablet was determined from the…

Complexation Effect on Redox Potential of Iron(III)-Iron(II) Couple: A Simple Potentiometric Experiment

ERIC Educational Resources Information Center

Rizvi, Masood Ahmad; Syed, Raashid Maqsood; Khan, Badruddin

2011-01-01

A titration curve with multiple inflection points results when a mixture of two or more reducing agents with sufficiently different reduction potentials are titrated. In this experiment iron(II) complexes are combined into a mixture of reducing agents and are oxidized to the corresponding iron(III) complexes. As all of the complexes involve the…

A new titration system of a novel split-type superconducting magnet NMR spectrometer.

PubMed

Kitagawa, Isao; Tanaka, Hideki; Okada, Michiya; Kitaguchi, Hitoshi; Kohzuma, Takamitsu

2008-12-01

A new titration system for studying protein-ligand interactions has been developed. In this system, the sample solution is circulated in the route formed by an access path in a split superconducting magnet to maintain a constant protein concentration during the titration experiments. A concentration-control procedure for the ligand/protein ratio is devised, and the ligand/protein ratio is well controlled by this apparatus.

Competitive counterion complexation allows the true host : guest binding constants from a single titration by ionic receptors.

PubMed

Pessêgo, Márcia; Basílio, Nuno; Muñiz, M Carmen; García-Río, Luis

2016-07-06

Counterion competitive complexation is a background process currently ignored by using ionic hosts. Consequently, guest binding constants are strongly affected by the design of the titration experiments in such a way that the results are dependent on the guest concentration and on the presence of added salts, usually buffers. In the present manuscript we show that these experimental difficulties can be overcome by just considering the counterion competitive complexation. Moreover a single titration allows us to obtain not only the true binding constants but also the stoichiometry of the complex showing the formation of 1 : 1 : 1 (host : guest : counterion) complexes. The detection of high stoichiometry complexes is not restricted to a single titration experiment but also to a displacement assay where both competitive and competitive-cooperative complexation models are taken into consideration.

Quantification of Protein-Ligand Interactions by Laser Electrospray Mass Spectrometry

NASA Astrophysics Data System (ADS)

Archer, Jieutonne J.; Karki, Santosh; Shi, Fengjian; Sistani, Habiballah; Levis, Robert J.

2018-04-01

Laser electrospray mass spectrometry (LEMS) measurement of the dissociation constant (Kd) for hen egg white lysozyme (HEWL) and N,N',N″-triacetylchitotriose (NAG3) revealed an apparent Kd value of 313.2 ± 25.9 μM for the ligand titration method. Similar measurements for N,N',N″,N″'-tetraacetylchitotetraose (NAG4) revealed an apparent Kd of 249.3 ± 13.6 μM. An electrospray ionization mass spectrometry (ESI-MS) experiment determined a Kd value of 9.8 ± 0.6 μM. In a second LEMS approach, a calibrated measurement was used to determine a Kd value of 6.8 ± 1.5 μM for NAG3. The capture efficiency of LEMS was measured to be 3.6 ± 1.8% and is defined as the fraction of LEMS sample detected after merging with the ESI plume. When the dilution is factored into the ligand titration measurement, the adjusted Kd value was 11.3 μM for NAG3 and 9.0 μM for NAG4. The calibration method for measuring Kd developed in this study can be applied to solutions containing unknown analyte concentrations. [Figure not available: see fulltext.

A Computer-Based Simulation of an Acid-Base Titration

ERIC Educational Resources Information Center

Boblick, John M.

1971-01-01

Reviews the advantages of computer simulated environments for experiments, referring in particular to acid-base titrations. Includes pre-lab instructions and a sample computer printout of a student's use of an acid-base simulation. Ten references. (PR)

Macromolecular and solution properties of Cepacian: the exopolysaccharide produced by a strain of Burkholderia cepacia isolated from a cystic fibrosis patient.

PubMed

Sist, Paola; Cescutti, Paola; Skerlavaj, Silvia; Urbani, Ranieri; Leitão, Jorge H; Sá-Correia, Isabel; Rizzo, Roberto

2003-09-01

Light scattering and viscosity measurements were carried out on the previously chemically characterised exopolysaccharide produced by a strain of Burkholderia cepacia isolated from a cystic fibrosis patient. The same exopolysaccharide was also produced by other clinical strains in different laboratories. Therefore, the name Cepacian is now proposed for this exopolysaccharide. Experiments performed as a function of the ionic strength on the native polymer revealed a change in the overall shape of the polymer at low ionic strength. This behaviour was absent in the de-acetylated sample. Potentiometric titrations and light scattering experiments carried out on the acidic form of the native polymer revealed the formation of macromolecular aggregates with a stoichiometry n and 2n stabilised by interactions involving the uronic acid residues.

Kinetics of bacterial potentiometric titrations: the effect of equilibration time on buffering capacity of Pantoea agglomerans suspensions.

PubMed

Kapetas, Leon; Ngwenya, Bryne T; Macdonald, Alan M; Elphick, Stephen C

2011-07-15

Several recent studies have made use of continuous acid-base titration data to describe the surface chemistry of bacterial cells as a basis for accurately modelling metal adsorption to bacteria and other biomaterials of potential industrial importance. These studies do not share a common protocol; rather they titrate in different pH ranges and they use different stability criteria to define equilibration time during titration. In the present study we investigate the kinetics of bacterial titrations and test the effect they have on the derivation of functional group concentrations and acidity constants. We titrated suspensions of Pantoea agglomerans by varying the equilibration time between successive titrant additions until stability of 0.1 or 0.001 mV s(-1) was attained. We show that under longer equilibration times, titration results are less reproducible and suspensions exhibit marginally higher buffering. Fluorescence images suggest that cell lysis is not responsible for these effects. Rather, high DOC values and titration reversibility hysterisis after long equilibration times suggest that variability in buffering is due to the presence of bacterial exudates, as demonstrated by titrating supernatants separated from suspensions of different equilibration times. It is recommended that an optimal equilibration time is always determined with variable stability control and preliminary reversibility titration experiments. Copyright © 2011 Elsevier Inc. All rights reserved.

Ion-selective electrodes in potentiometric titrations; a new method for processing and evaluating titration data.

PubMed

Granholm, Kim; Sokalski, Tomasz; Lewenstam, Andrzej; Ivaska, Ari

2015-08-12

A new method to convert the potential of an ion-selective electrode to concentration or activity in potentiometric titration is proposed. The advantage of this method is that the electrode standard potential and the slope of the calibration curve do not have to be known. Instead two activities on the titration curve have to be estimated e.g. the starting activity before the titration begins and the activity at the end of the titration in the presence of large excess of titrant. This new method is beneficial when the analyte is in a complexed matrix or in a harsh environment which affects the properties of the electrode and the traditional calibration procedure with standard solutions cannot be used. The new method was implemented both in a method of linearization based on the Grans's plot and in determination of the stability constant of a complex and the concentration of the complexing ligand in the sample. The new method gave accurate results when using titrations data from experiments with samples of known composition and with real industrial harsh black liquor sample. A complexometric titration model was also developed. Copyright © 2015 Elsevier B.V. All rights reserved.

Measuring titratable alkalinity by single versus double endpoint titration: An evaluation in two cyprinodont species and implications for characterizing net H+ flux in aquatic organisms.

PubMed

Brix, Kevin V; Wood, Chris M; Grosell, Martin

2013-01-01

In this study, Na(+) uptake and acid-base balance in the euryhaline pupfish Cyprinodon variegatus variegatus were characterized when fish were exposed to pH 4.5 freshwater (7mM Na(+)). Similar to the related cyprinodont, Fundulus heteroclitus, Na(+) uptake was significantly inhibited when exposed to low pH water. However, it initially appeared that C. v. variegatus increased apparent net acid excretion at low pH relative to circumneutral pH. This result is opposite to previous observations for F. heteroclitus under similar conditions where fish were observed to switch from apparent net H(+) excretion at circumneutral pH to apparent net H(+) uptake at low pH. Further investigation revealed disparate observations between these studies were the result of using double endpoint titrations to measure titratable alkalinity fluxes in the current study, while the earlier study utilized single endpoint titrations to measure these fluxes (i.e.,. Cyprinodon acid-base transport is qualitatively similar to Fundulus when characterized using single endpoint titrations). This led to a comparative investigation of these two methods. We hypothesized that either the single endpoint methodology was being influenced by a change in the buffer capacity of the water (e.g., mucus being released by the fish) at low pH, or the double endpoint methodology was not properly accounting for ammonia flux by the fish. A series of follow-up experiments indicated that buffer capacity of the water did not change significantly, that excretion of protein (a surrogate for mucus) was actually reduced at low pH, and that the double endpoint methodology does not properly account for NH(3) excretion by fish under low pH conditions. As a result, it overestimates net H(+) excretion during low pH exposure. After applying the maximum possible correction for this error (i.e., assuming that all ammonia is excreted as NH(3)), the double endpoint methodology indicates that net H(+) transport was reduced to effectively zero in both species at pH 4.5. However, significant differences between the double endpoint (no net H(+) transport at low pH) and single endpoint titrations (net H(+) uptake at low pH) remain to be explained. Copyright © 2012 Elsevier Inc. All rights reserved.

Filtrates & Residues: Olfactory Titration.

ERIC Educational Resources Information Center

Wood, John T.; Eddy, Roberta M.

1996-01-01

Presents an experiment that uses a unique acid-base indicator--the odor of raw onion--to indicate the end point of the titration of sodium hydroxide with hydrochloric acid. Allows the student to detect the completion of the neutralization reaction by olfaction rather than sight. (JRH)

Native ESI Mass Spectrometry Can Help to Avoid Wrong Interpretations from Isothermal Titration Calorimetry in Difficult Situations

NASA Astrophysics Data System (ADS)

Wolff, Philippe; Da Veiga, Cyrielle; Ennifar, Eric; Bec, Guillaume; Guichard, Gilles; Burnouf, Dominique; Dumas, Philippe

2017-02-01

We studied by native ESI-MS the binding of various DNA-polymerase-derived peptides onto DNA-polymerase processivity rings from Escherichia coli, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. These homodimeric rings present two equivalent specific binding sites, which leads to successive formation during a titration experiment of singly- and doubly occupied rings. By using the ESI-MS free-ring spectrum as a ruler, we derived by robust linear regression the fractions of the different ring species at each step of a titration experiment. These results led to accurate Kd values (from 0.03 to 0.5 μM) along with the probability of peptide loss due to gas phase dissociation (GPD). We show that this good quality is due to the increased information content of a titration experiment with a homodimer. Isothermal titration calorimetry (ITC) led with the same binding model to Kd(ITC) values systematically higher than their ESI-MS counterparts and, often, to poor fit of the ITC curves. A processing with two competing modes of binding on the same site requiring determination of two (Kd, ΔH) pairs greatly improved the fits and yielded a second Kd(ITC) close to Kd(ESI-MS). The striking features are: (1) ITC detected a minor binding mode ( 20%) of `low-affinity' that did not appear with ESI-MS; (2) the simplest processing of ITC data with only one (Kd, ΔH) pair led wrongly to the Kd of the low-affinity binding mode but to the ΔH of the high-affinity binding mode. Analogous misleading results might well exist in published data based on ITC experiments.

Native ESI Mass Spectrometry Can Help to Avoid Wrong Interpretations from Isothermal Titration Calorimetry in Difficult Situations.

PubMed

Wolff, Philippe; Da Veiga, Cyrielle; Ennifar, Eric; Bec, Guillaume; Guichard, Gilles; Burnouf, Dominique; Dumas, Philippe

2017-02-01

We studied by native ESI-MS the binding of various DNA-polymerase-derived peptides onto DNA-polymerase processivity rings from Escherichia coli, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. These homodimeric rings present two equivalent specific binding sites, which leads to successive formation during a titration experiment of singly- and doubly occupied rings. By using the ESI-MS free-ring spectrum as a ruler, we derived by robust linear regression the fractions of the different ring species at each step of a titration experiment. These results led to accurate K d values (from 0.03 to 0.5 μM) along with the probability of peptide loss due to gas phase dissociation (GPD). We show that this good quality is due to the increased information content of a titration experiment with a homodimer. Isothermal titration calorimetry (ITC) led with the same binding model to K d (ITC) values systematically higher than their ESI-MS counterparts and, often, to poor fit of the ITC curves. A processing with two competing modes of binding on the same site requiring determination of two (K d , ΔH) pairs greatly improved the fits and yielded a second K d (ITC) close to K d (ESI-MS). The striking features are: (1) ITC detected a minor binding mode (~20%) of 'low-affinity' that did not appear with ESI-MS; (2) the simplest processing of ITC data with only one (K d , ΔH) pair led wrongly to the Kd of the low-affinity binding mode but to the ΔH of the high-affinity binding mode. Analogous misleading results might well exist in published data based on ITC experiments. Graphical Abstract ᅟ.

Determination of Acidity Constants by Gradient Flow-Injection Titration

ERIC Educational Resources Information Center

Conceicao, Antonio C. L.; Minas da Piedade, Manuel E.

2006-01-01

A three-hour laboratory experiment, designed for an advanced undergraduate course in instrumental analysis that illustrates the application of the gradient chamber flow-injection titration (GCFIT) method with spectrophotometric detection to determine acidity constants is presented. The procedure involves the use of an acid-base indicator to obtain…

Biomolecule-nanoparticle interactions: Elucidation of the thermodynamics by isothermal titration calorimetry.

PubMed

Huang, Rixiang; Lau, Boris L T

2016-05-01

Nanomaterials (NMs) are often exposed to a broad range of biomolecules of different abundances. Biomolecule sorption driven by various interfacial forces determines the surface structure and composition of NMs, subsequently governs their functionality and the reactivity of the adsorbed biomolecules. Isothermal titration calorimetry (ITC) is a nondestructive technique that quantifies thermodynamic parameters through in-situ measurement of the heat absorption or release associated with an interaction. This review highlights the recent applications of ITC in understanding the thermodynamics of interactions between various nanoparticles (NPs) and biomolecules. Different aspects of a typical ITC experiment that are crucial for obtaining accurate and meaningful data, as well as the strengths, weaknesses, and challenges of ITC applications to NP research were discussed. ITC reveals the driving forces behind biomolecule-NP interactions and the effects of the physicochemical properties of both NPs and biomolecules by quantifying the crucial thermodynamics parameters (e.g., binding stoichiometry, ΔH, ΔS, and ΔG). Complimentary techniques would strengthen the interpretation of ITC results for a more holistic understanding of biomolecule-NP interactions. The thermodynamic information revealed by ITC and its complimentary characterizations is important for understanding biomolecule-NP interactions that are fundamental to the biomedical and environmental applications of NMs and their toxicological effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Acid-base properties of the alumina surface: influence of the titration procedures on the microcalorimetric results.

PubMed

Morel, Jean-Pierre; Marmier, Nicolas; Hurel, Charlotte; Morel-Desrosiers, Nicole

2009-10-01

The enthalpy changes associated with the protonation and deprotonation of an alumina surface have been determined on the basis of microcalorimetry experiments and acid-base potentiometric titrations at 25 degrees C. It has been shown that the results may vary significantly according to the experimental procedure. In order to do so, the potentiometric and microcalorimetric titrations have been carried out first from an acidic pH to basic pH and second from a pH near the pH(zpc) of alumina to acidic or basic pH. It has been demonstrated that the pK(a) values deduced from the potentiometric titrations are the same whatever the experimental protocol whereas the only way to obtain meaningful enthalpies of proton exchange is to carry out microcalorimetric titrations by starting around the point of zero charge.

Assessment of residual active chlorine in sodium hypochlorite solutions after dissolution of porcine incisor pulpal tissue.

PubMed

Clarkson, R M; Smith, T K; Kidd, B A; Evans, G E; Moule, A J

2013-12-01

In previous studies, surfactant-containing Hypochlor brands of sodium hypochlorite showed better tissue solubilizing abilities than Milton; differences not explained by original active chlorine content or presence of surfactant. It was postulated that exhaustion of active chlorine content could explain differences. This study aimed to assess whether Milton's poorer performance was due to exhaustion of active chlorine. Parallel experiments assessed the influence of titration methods, and the presence of chlorates, on active chlorine measurements. Time required to dissolve one or groups of 10 samples of porcine incisor pulp samples in Milton was determined. Residual active chlorine was assessed by thermometric titration. Iodometric and thermometric titration was carried out on samples of Milton. Chlorate content was also measured. Dissolution of single and 10 pulp samples caused a mean loss of 1% and 3% respectively of active chlorine, not being proportional to tissue dissolved. Thermometric ammonium ion titration resulted in 10% lower values than iodometric titration. Chlorate accounted for much of this difference. Depletion of active chlorine is not the reason for differences in tissue dissolving capabilities of Milton. Thermometric ammonium ion titration gives more accurate measurement of active chlorine content than iodometric titration. © 2013 Australian Dental Association.

Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

PubMed

El-Kersh, Karim; Ruf, Kathryn M; Smith, J Shaun

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

Differential Binding Models for Direct and Reverse Isothermal Titration Calorimetry.

PubMed

Herrera, Isaac; Winnik, Mitchell A

2016-03-10

Isothermal titration calorimetry (ITC) is a technique to measure the stoichiometry and thermodynamics from binding experiments. Identifying an appropriate mathematical model to evaluate titration curves of receptors with multiple sites is challenging, particularly when the stoichiometry or binding mechanism is not available. In a recent theoretical study, we presented a differential binding model (DBM) to study calorimetry titrations independently of the interaction among the binding sites (Herrera, I.; Winnik, M. A. J. Phys. Chem. B 2013, 117, 8659-8672). Here, we build upon our DBM and show its practical application to evaluate calorimetry titrations of receptors with multiple sites independently of the titration direction. Specifically, we present a set of ordinary differential equations (ODEs) with the general form d[S]/dV that can be integrated numerically to calculate the equilibrium concentrations of free and bound species S at every injection step and, subsequently, to evaluate the volume-normalized heat signal (δQ(V) = δq/dV) of direct and reverse calorimetry titrations. Additionally, we identify factors that influence the shape of the titration curve and can be used to optimize the initial concentrations of titrant and analyte. We demonstrate the flexibility of our updated DBM by applying these differentials and a global regression analysis to direct and reverse calorimetric titrations of gadolinium ions with multidentate ligands of increasing denticity, namely, diglycolic acid (DGA), citric acid (CIT), and nitrilotriacetic acid (NTA), and use statistical tests to validate the stoichiometries for the metal-ligand pairs studied.

An on-line potentiometric sequential injection titration process analyser for the determination of acetic acid.

PubMed

van Staden, J F; Mashamba, Mulalo G; Stefan, Raluca I

2002-09-01

An on-line potentiometric sequential injection titration process analyser for the determination of acetic acid is proposed. A solution of 0.1 mol L(-1) sodium chloride is used as carrier. Titration is achieved by aspirating acetic acid samples between two strong base-zone volumes into a holding coil and by channelling the stack of well-defined zones with flow reversal through a reaction coil to a potentiometric sensor where the peak widths were measured. A linear relationship between peak width and logarithm of the acid concentration was obtained in the range 1-9 g/100 mL. Vinegar samples were analysed without any sample pre-treatment. The method has a relative standard deviation of 0.4% with a sample frequency of 28 samples per hour. The results revealed good agreement between the proposed sequential injection and an automated batch titration method.

Titration and HPLC Characterization of Kombucha Fermentation: A Laboratory Experiment in Food Analysis

ERIC Educational Resources Information Center

Miranda, Breanna; Lawton, Nicole M.; Tachibana, Sean R.; Swartz, Natasja A.; Hall, W. Paige

2016-01-01

Quantification of the many constituents that make up our food, whether they are desirable (vitamins, antioxidants, nutrients) or undesirable (pesticides, toxins), is one of the most practical applications of chemistry. In this study, kombucha, a popular fermented tea beverage, was analyzed using acid-base titration and high-performance liquid…

Optimizing Glycemic Control Through Titration of Insulin Glargine 100 U/mL: A Review of Current and Future Approaches with a Focus on Asian Populations.

PubMed

Deerochanawong, Chaicharn; Bajpai, Shailendra; Dwipayana, I Made Pande; Hussein, Zanariah; Mabunay, Maria Aileen; Rosales, Reynaldo; Tsai, Shih-Tzer; Tsang, Man Wo

2017-12-01

Various data have demonstrated inadequate glycemic control amongst Asians with type 2 diabetes mellitus (T2DM), possibly on account of suboptimal titration of basal insulin-an issue which needs to be further examined. Here we review the available global and Asia-specific data on titration of basal insulin, with a focus on the use of insulin glargine 100 U/mL (Gla-100). We also discuss clinical evidence on the efficacy and safety of titrating Gla-100, different approaches to titration, including some of the latest technological advancements, and guidance on the titration of basal insulin from international and local Asian guidelines. The authors also provide their recommendations for the initiation and titration of basal insulin for Asian populations. Discussion of the data included in this review and in relation to the authors' clinical experience with treating T2DM in Asian patients is also included. Briefly, clinical studies demonstrate the achievement of adequate glycemic control in adults with T2DM through titration of Gla-100. However, studies investigating approaches to titration, specifically in Asian populations, are lacking and need to be conducted. Given that the management of insulin therapy is a multidisciplinary team effort involving endocrinologists, primary care physicians, nurse educators, and patients, greater resources and education targeted at these groups are needed regarding the optimal titration of basal insulin. Technological advancements in the form of mobile or web-based applications for automated dose adjustment can aid different stakeholders in optimizing the dose of basal insulin, enabling a larger number of patients in Asia to reach their target glycemic goals with improved outcomes.

Parametric changes in response equilibrium during an intra-cranial self stimulation (ICSS) task: can reward value be assessed independently of absolute threshold?

PubMed

Easterling, K W; Holtzman, S G

1997-01-01

Traditional ICSS methodologies have attempted to evaluate changes in the rewarding value of brain stimulation by assessing the lowest value of the stimulation that will support responding. However, orderly changes in suprathreshold indicants of hedonic magnitude such as titration point have been shown. In the present experiments, rats were trained to respond on two ICSS autotitration schedules in which every response on one lever produced stimulation of the medial forebrain bundle, and every Xth response decreased either the stimulation current or the stimulation frequency. At any time, a response on a second "reset" lever restored the stimulation current or frequency available on the stimulation lever to its starting level and operationally defined changes in "reward value". In order to study this titration point measure, two response requirements (responses/stepdown; step size) and two stimulation parameters (initial stimulation level; train duration) were systematically varied. Under both current and frequency titration schedules, data indicated that response rate and titration point remained stable over repeated trials and multiple testing days--parameters being constant. Across all conditions, compared to the frequency titration schedule, subjects responding under the current titration schedule showed significantly higher titration points and lower rates of responding. Indicating the independence of rate and titration point data, parametric manipulations did not affect titration point and rate data concurrently. Results support the conclusion that titration point is a relative measure of "reward value" that is generally independent of response rate, but that is affected by manipulations that alter the amount of stimulation available between "resets". Additional work is needed in order to determine the relationship between the magnitude of stimulation needed to maintain minimal responding and that needed to maintain response equilibrium in an autotitration task.

Chromogenic sensing of biological thiols using squarylium dye.

PubMed

Shin, In-Sub; Gwon, Seon-Yeong; Kim, Sung-Hoon

2014-01-01

A new highly selective probe for biothiols, squarylium dye (SQ), was designed and synthesized. The probe displayed a color change from blue to colorless upon reaction with biothilos such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH). The competition experiments revealed that no obvious interference was observed by performing the titration with the mixtures of Cys and other amino acids. The results indicated that SQ was highly selective for Cys detection. Moreover, SQ could also serve as a "naked-eye" probe for Cys with a minimum detectable concentration of approximately 4 μM. Copyright © 2013 Elsevier B.V. All rights reserved.

Charge Density Quantification of Polyelectrolyte Polysaccharides by Conductometric Titration: An Analytical Chemistry Experiment

ERIC Educational Resources Information Center

Farris, Stefano; Mora, Luigi; Capretti, Giorgio; Piergiovanni, Luciano

2012-01-01

An easy analytical method for determination of the charge density of polyelectrolytes, including polysaccharides and other biopolymers, is presented. The basic principles of conductometric titration, which is used in the pulp and paper industry as well as in colloid and interface science, were adapted to quantify the charge densities of a…

Isothermal Titration Calorimetry and Macromolecular Visualization for the Interaction of Lysozyme and Its Inhibitors

ERIC Educational Resources Information Center

Wei, Chin-Chuan; Jensen, Drake; Boyle, Tiffany; O'Brien, Leah C.; De Meo, Cristina; Shabestary, Nahid; Eder, Douglas J.

2015-01-01

To provide a research-like experience to upper-division undergraduate students in a biochemistry teaching laboratory, isothermal titration calorimetry (ITC) is employed to determine the binding constants of lysozyme and its inhibitors, N-acetyl glucosamine trimer (NAG[subscript 3]) and monomer (NAG). The extremely weak binding of lysozyme/NAG is…

Manipulating Protein-Protein Interactions in Nonribosomal Peptide Synthetase Type II Peptidyl Carrier Proteins.

PubMed

Jaremko, Matt J; Lee, D John; Patel, Ashay; Winslow, Victoria; Opella, Stanley J; McCammon, J Andrew; Burkart, Michael D

2017-10-10

In an effort to elucidate and engineer interactions in type II nonribosomal peptide synthetases, we analyzed biomolecular recognition between the essential peptidyl carrier proteins and adenylation domains using nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics, and mutational studies. Three peptidyl carrier proteins, PigG, PltL, and RedO, in addition to their cognate adenylation domains, PigI, PltF, and RedM, were investigated for their cross-species activity. Of the three peptidyl carrier proteins, only PigG showed substantial cross-pathway activity. Characterization of the novel NMR solution structure of holo-PigG and molecular dynamics simulations of holo-PltL and holo-PigG revealed differences in structures and dynamics of these carrier proteins. NMR titration experiments revealed perturbations of the chemical shifts of the loop 1 residues of these peptidyl carrier proteins upon their interaction with the adenylation domain. These experiments revealed a key region for the protein-protein interaction. Mutational studies supported the role of loop 1 in molecular recognition, as mutations to this region of the peptidyl carrier proteins significantly modulated their activities.

A visual detection of protein content based on titration of moving reaction boundary electrophoresis.

PubMed

Wang, Hou-Yu; Guo, Cheng-Ye; Guo, Chen-Gang; Fan, Liu-Yin; Zhang, Lei; Cao, Cheng-Xi

2013-04-24

A visual electrophoretic titration method was firstly developed from the concept of moving reaction boundary (MRB) for protein content analysis. In the developed method, when the voltage was applied, the hydroxide ions in the cathodic vessel moved towards the anode, and neutralized the carboxyl groups of protein immobilized via highly cross-linked polyacrylamide gel (PAG), generating a MRB between the alkali and the immobilized protein. The boundary moving velocity (V(MRB)) was as a function of protein content, and an acid-base indicator was used to denote the boundary displacement. As a proof of concept, standard model proteins and biological samples were chosen for the experiments to study the feasibility of the developed method. The experiments revealed that good linear calibration functions between V(MRB) and protein content (correlation coefficients R>0.98). The experiments further demonstrated the following merits of developed method: (1) weak influence of non-protein nitrogen additives (e.g., melamine) adulterated in protein samples, (2) good agreement with the classic Kjeldahl method (R=0.9945), (3) fast measuring speed in total protein analysis of large samples from the same source, and (4) low limit of detection (0.02-0.15 mg mL(-1) for protein content), good precision (R.S.D. of intra-day less than 1.7% and inter-day less than 2.7%), and high recoveries (105-107%). Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Effect of temperature on the acid-base properties of the alumina surface: microcalorimetry and acid-base titration experiments.

PubMed

Morel, Jean-Pierre; Marmier, Nicolas; Hurel, Charlotte; Morel-Desrosiers, Nicole

2006-06-15

Sorption reactions on natural or synthetic materials that can attenuate the migration of pollutants in the geosphere could be affected by temperature variations. Nevertheless, most of the theoretical models describing sorption reactions are at 25 degrees C. To check these models at different temperatures, experimental data such as the enthalpies of sorption are thus required. Highly sensitive microcalorimeters can now be used to determine the heat effects accompanying the sorption of radionuclides on oxide-water interfaces, but enthalpies of sorption cannot be extracted from microcalorimetric data without a clear knowledge of the thermodynamics of protonation and deprotonation of the oxide surface. However, the values reported in the literature show large discrepancies and one must conclude that, amazingly, this fundamental problem of proton binding is not yet resolved. We have thus undertaken to measure by titration microcalorimetry the heat effects accompanying proton exchange at the alumina-water interface at 25 degrees C. Based on (i) the surface sites speciation provided by a surface complexation model (built from acid-base titrations at 25 degrees C) and (ii) results of the microcalorimetric experiments, calculations have been made to extract the enthalpic variations associated respectively to first and second deprotonation of the alumina surface. Values obtained are deltaH1 = 80+/-10 kJ mol(-1) and deltaH2 = 5+/-3 kJ mol(-1). In a second step, these enthalpy values were used to calculate the alumina surface acidity constants at 50 degrees C via the van't Hoff equation. Then a theoretical titration curve at 50 degrees C was calculated and compared to the experimental alumina surface titration curve. Good agreement between the predicted acid-base titration curve and the experimental one was observed.

Determining the folding and binding free energy of DNA-based nanodevices and nanoswitches using urea titration curves

PubMed Central

Idili, Andrea

2017-01-01

Abstract DNA nanotechnology takes advantage of the predictability of DNA interactions to build complex DNA-based functional nanoscale structures. However, when DNA functional and responsive units that are based on non-canonical DNA interactions are employed it becomes quite challenging to predict, understand and control their thermodynamics. In response to this limitation, here we demonstrate the use of isothermal urea titration experiments to estimate the free energy involved in a set of DNA-based systems ranging from unimolecular DNA-based nanoswitches to more complex DNA folds (e.g. aptamers) and nanodevices. We propose here a set of fitting equations that allow to analyze the urea titration curves of these DNA responsive units based on Watson–Crick and non-canonical interactions (stem-loop, G-quadruplex, triplex structures) and to correctly estimate their relative folding and binding free energy values under different experimental conditions. The results described herein will pave the way toward the use of urea titration experiments in the field of DNA nanotechnology to achieve easier and more reliable thermodynamic characterization of DNA-based functional responsive units. More generally, our results will be of general utility to characterize other complex supramolecular systems based on different biopolymers. PMID:28605461

On the acid-base properties of humic acid in soil.

PubMed

Cooke, James D; Hamilton-Taylor, John; Tipping, Edward

2007-01-15

Humic acid was isolated from three contrasting organic-rich soils and acid-base titrations performed over a range of ionic strengths. Results obtained were unlike most humic acid data sets; they showed a greater ionic strength dependency at low pH than at high pH. Forward- and back-titrations with the base and acid revealed hysteresis, particularly at low pH. Previous authors attributed this type of hysteresis to humic acid aggregates-created during the isolation procedure-being redissolved during titration as the pH increased and regarded the results as artificial. However, forward- and back-titrations with organic-rich soils also demonstrated a similar hysteretic behavior. These observations indicate (i) that titrations of humic acid in aggregated form (as opposed to the more usual dissolved form) are more representative of the acid-base properties of humic acid in soil and (ii) that the ionic strength dependency of proton binding in humic acid is related to its degree of aggregation. Thus, the current use of models based on data from dissolved humic substances to predictthe acid-base properties of humic acid in soil under environmental conditions may be flawed and could substantially overestimate their acid buffering capacity.

The acid-base buffer capacity of podzolic soils and its changes under the impact of treatment with the Mehra-Jackson and Tamm reagents

NASA Astrophysics Data System (ADS)

Maksimova, Yu. G.; Maryakhina, N. N.; Tolpeshta, I. I.; Sokolova, T. A.

2010-10-01

The acid-base buffer capacity before and after the treatment with the Mehra-Jackson and Tamm reagents was assessed by continuous potentiometric titration for the main genetic horizons of two profiles of podzolic soils in the Central Forest State Reserve. The total buffer capacity was calculated in the pH range from the initial titration point (ITP) to 3 for the acid titration and from the ITP to 10 for the base titration, as well as the buffer capacities in the pH intervals of 0.25. It was found that both treatments abruptly decreased the base buffer capacity, which reached 70-90% in the E horizons. The high direct linear correlation of the difference between the total base buffer capacities before and after each treatment with the content of Fe in the Tamm extract was revealed. From the results obtained, a conclusion was drawn that finely dispersed Fe hydroxides were the main solid-phase constituents ensuring the base buffer capacity, and the deprotonation of hydroxyl groups on the surface of Fe hydroxides was the essential buffer reaction during the base titration.

Computer Series, 88.

ERIC Educational Resources Information Center

Moore, John W., Ed.

1987-01-01

Describes two experiments in college chemistry which use microcomputers. One experiment deals with chemical oscillations, while the other involves colorimeter titration with laser excitation and computer-interfaced endpoint detection. (TW)

A more detailed picture of the interactions between virtual screening-derived hits and the DNA G-quadruplex: NMR, molecular modelling and ITC studies.

PubMed

Trotta, Roberta; De Tito, Stefano; Lauri, Ilaria; La Pietra, Valeria; Marinelli, Luciana; Cosconati, Sandro; Martino, Luigi; Conte, Maria R; Mayol, Luciano; Novellino, Ettore; Randazzo, Antonio

2011-08-01

The growing amount of literature about G-quadruplex DNA clearly demonstrates that such a structure is no longer viewed as just a biophysical strangeness but it is instead being considered as an important target for the treatment of various human disorders such as cancers or venous thrombosis. In this scenario, with the aim of finding brand new molecular scaffolds able to interact with the groove of the DNA quadruplex [d(TGGGGT)](4), we recently performed a successful structure-based virtual screening (VS) campaign. As a result, six molecules were found to be somehow groove binders. Herein, we report the results of novel NMR titration experiments of these VS-derived ligands with modified quadruplexes, namely [d(TGG(Br)GGT)](4) and [d(TGGGG(Br)T)](4). The novel NMR spectroscopy experiments combined with molecular modelling studies, allow for a more detailed picture of the interaction between each binder and the quadruplex DNA. Noteworthy, isothermal titration calorimetry (ITC) measurements on the above-mentioned compounds revealed that 2, 4, and 6 besides their relatively small dimensions bind the DNA quadruplex [d(TGGGGT)](4) with higher affinity than distamycin A, to the best of our knowledge, the most potent groove binder identified thus far. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Blocking the Interactions between Calcium-Bound S100A12 Protein and the V Domain of RAGE Using Tranilast

PubMed Central

Chiou, Jian Wei; Fu, Brian

2016-01-01

The receptor for advanced glycation end products (RAGE), a transmembrane receptor in the immunoglobulin superfamily, is involved in several inflammatory processes. RAGE induces cellular signaling pathways upon binding with various ligands, such as advanced glycation end products (AGEs), β-amyloids, and S100 proteins. The solution structure of S100A12 and the V ligand-binding region of RAGE have been reported previously. Using heteronuclear NMR spectroscopy to conduct 1H–15N heteronuclear single quantum coherence (HSQC) titration experiments, we identified and mapped the binding interface between S100A12 and the V domain of RAGE. The NMR chemical shift data were used as the constraints for the High Ambiguity Driven biomolecular DOCKing (HADDOCK) calculation to generate a structural model of the S100A12–V domain complex. In addition, tranilast (an anti-allergic drug) showed strong interaction with S100A12 in the 1H–15N HSQC titration, fluorescence experiments, and WST-1 assay. The results also indicated that tranilast was located at the binding site between S100A12 and the V domain, blocking interaction between these two proteins. Our results provide the mechanistic details for a structural model and reveal a potential precursor for an inhibitor for pro-inflammatory diseases, which could be useful for the development of new drugs. PMID:27598566

Study on interaction of mangiferin to insulin and glucagon in ternary system

NASA Astrophysics Data System (ADS)

Lin, Hui; Chen, Rui; Liu, Xiaoyan; Sheng, Fenling; Zhang, Haixia

2010-05-01

The binding of mangiferin to insulin and glucagon was investigated in the presence and absence of another Peptide by optical spectroscopy. Fluorescence titration experiments revealed that mangiferin quenched the intrinsic fluorescence of insulin and glucagon by static quenching. The ratios of binding constants of glucagon-mangiferin to insulin-mangiferin at different temperatures were calculated in "pure" and ternary system, respectively. The results indicated that the Peptides were competitive with each other to act on mangiferin. Values of the thermodynamic parameters and the experiments of pH effect proved that the key interacting forces between mangiferin and the Peptides were hydrophobic interaction. In addition, UV-vis absorption, synchronous fluorescence and Fourier transform infrared measurements showed that the conformation of insulin and glucagon were changed after adding mangiferin.

A stable and convenient protein electrophoresis titration device with bubble removing system.

PubMed

Zhang, Qiang; Fan, Liu-Yin; Li, Wen-Lin; Cong, Feng-Song; Zhong, Ran; Chen, Jing-Jing; He, Yu-Chen; Xiao, Hua; Cao, Cheng-Xi

2017-07-01

Moving reaction boundary titration (MRBT) has a potential application to immunoassay and protein content analysis with high selectivity. However, air bubbles often impair the accuracy of MRBT, and the leakage of electrolyte greatly decreases the safety and convenience of electrophoretic titration. Addressing these two issues a reliable MRBT device with modified electrolyte chamber of protein titration was designed. Multiphysics computer simulation was conducted for optimization according to two-phase flow. The single chamber was made of two perpendicular cylinders with different diameters. After placing electrophoretic tube, the resident air in the junction next to the gel could be eliminated by a simple fast electrolyte flow. Removing the electrophoretic tube automatically prevented electrolyte leakage at the junction due to the gravity-induced negative pressure within the chamber. Moreover, the numerical simulation and experiments showed that the improved MRBT device has following advantages: (i) easy and rapid setup of electrophoretic tube within 20 s; (ii) simple and quick bubble dissipates from the chamber of titration within 2 s; (iii) no electrolyte leakage from the two chambers: and (iv) accurate protein titration and safe instrumental operation. The developed technique and apparatus greatly improves the performance of the previous MRBT device, and providing a new route toward practical application. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Taylor-Pashow, K.; Fondeur, F.; White, T.

Savannah River National Laboratory (SRNL) was tasked with identifying and developing at least one, but preferably two methods for quantifying the suppressor in the Next Generation Solvent (NGS) system. The suppressor is a guanidine derivative, N,N',N"-tris(3,7-dimethyloctyl)guanidine (TiDG). A list of 10 possible methods was generated, and screening experiments were performed for 8 of the 10 methods. After completion of the screening experiments, the non-aqueous acid-base titration was determined to be the most promising, and was selected for further development as the primary method. {sup 1}H NMR also showed promising results from the screening experiments, and this method was selected formore » further development as the secondary method. Other methods, including {sup 36}Cl radiocounting and ion chromatography, also showed promise; however, due to the similarity to the primary method (titration) and the inability to differentiate between TiDG and TOA (tri-n-ocytlamine) in the blended solvent, {sup 1}H NMR was selected over these methods. Analysis of radioactive samples obtained from real waste ESS (extraction, scrub, strip) testing using the titration method showed good results. Based on these results, the titration method was selected as the method of choice for TiDG measurement. {sup 1}H NMR has been selected as the secondary (back-up) method, and additional work is planned to further develop this method and to verify the method using radioactive samples. Procedures for analyzing radioactive samples of both pure NGS and blended solvent were developed and issued for the both methods.« less

Mini-Column Ion-Exchange Separation and Atomic Absorption Quantitation of Nickel, Cobalt, and Iron: An Undergraduate Quantitative Analysis Experiment.

ERIC Educational Resources Information Center

Anderson, James L.; And Others

1980-01-01

Presents an undergraduate quantitative analysis experiment, describing an atomic absorption quantitation scheme that is fast, sensitive and comparatively simple relative to other titration experiments. (CS)

Simultaneous addition of two ligands: a potential strategy for estimating divalent ion affinities in EF-hand proteins by isothermal titration calorimetry.

PubMed

Henzl, Michael T; Markus, Lindsey A; Davis, Meredith E; McMillan, Andrew T

2013-03-01

Capable of providing a detailed thermodynamic picture of noncovalent association reactions, isothermal titration calorimetry (ITC) has become a popular method for studying protein-ligand interactions. We routinely employ the technique to study divalent ion-binding by two-site EF-hand proteins from the parvalbumin- and polcalcin lineages. The combination of high Ca(2+) affinity and relatively low Mg(2+) affinity, and the attendant complication of parameter correlation, conspire to make the simultaneous extraction of binding constants and -enthalpies for both ions challenging. Although global analysis of multiple ITC experiments can overcome these hurdles, our current experimental protocol includes upwards of 10 titrations - requiring a substantial investment in labor, machine time, and material. This paper explores the potential for using a smaller suite of experiments that includes simultaneous titrations with Ca(2+) and Mg(2+) at different ratios of the two ions. The results obtained for four proteins, differing substantially in their divalent ion-binding properties, suggest that the approach has merit. The Ca(2+)- and Mg(2+)-binding constants afforded by the streamlined analysis are in reasonable agreement with those obtained from the standard analysis protocol. Likewise, the abbreviated analysis provides comparable values for the Ca(2+)-binding enthalpies. However, the streamlined analysis can yield divergent values for the Mg(2+)-binding enthalpies - particularly those for lower affinity sites. This shortcoming can be remedied, in large measure, by including data from a direct Ca(2+) titration in the presence of a high, fixed Mg(2+) concentration. Copyright © 2013. Published by Elsevier Inc.

Microscale Determination of Vitamin C by Weight Titrimetry

NASA Astrophysics Data System (ADS)

East, Gaston A.; Nascimento, Erica C.

2002-01-01

A laboratory experiment involving the quantitative microscale determination of ascorbic acid in pharmaceutical tablets of vitamin C by weight-titrimetry using (diacetoxyiodo)benzene as titrant and differential electrolytic potentiometry to locate the end-point is presented. The experiment affords an opportunity for students to explore nonconventional techniques such as the use of a novel organic oxidimetric titrant, titration in a semiaqueous medium, gravimetric titration, and an electrometric method of end-point detection using polarized electrodes. Synthesis, purification, and purity checking of the titrant may also be included in the project. Some advantages of the method are very low reagent consumption, low-cost equipment, improved sensitivity, and high precision and accuracy. Furthermore, the experiment will help the student to relate chemical analysis to everyday life.

Enzyme catalysis-electrophoresis titration for multiplex enzymatic assay via moving reaction boundary chip.

PubMed

Zhong, Ran; Xie, Haiyang; Kong, Fanzhi; Zhang, Qiang; Jahan, Sharmin; Xiao, Hua; Fan, Liuyin; Cao, Chengxi

2016-09-21

In this work, we developed the concept of enzyme catalysis-electrophoresis titration (EC-ET) under ideal conditions, the theory of EC-ET for multiplex enzymatic assay (MEA), and a related method based on a moving reaction boundary (MRB) chip with a collateral channel and cell phone imaging. As a proof of principle, the model enzymes horseradish peroxidase (HRP), laccase and myeloperoxidase (MPO) were chosen for the tests of the EC-ET model. The experiments revealed that the EC-ET model could be achieved via coupling EC with ET within a MRB chip; particularly the MEA analyses of catalysis rate, maximum rate, activity, Km and Kcat could be conducted via a single run of the EC-ET chip, systemically demonstrating the validity of the EC-ET theory. Moreover, the developed method had these merits: (i) two orders of magnitude higher sensitivity than a fluorescence microplate reader, (ii) simplicity and low cost, and (iii) fairly rapid (30 min incubation, 20 s imaging) analysis, fair stability (<5.0% RSD) and accuracy, thus validating the EC-ET method. Finally, the developed EC-ET method was used for the clinical assay of MPO activity in blood samples; the values of MPO activity detected via the EC-ET chip were in agreement with those obtained by a traditional fluorescence microplate reader, indicating the applicability of the EC-ET method. The work opens a window for the development of enzymatic research, enzyme assay, immunoassay, and point-of-care testing as well as titration, one of the oldest methods of analysis, based on a simple chip.

Energetics of Glutathione Binding to Human Eukaryotic Elongation Factor 1 Gamma: Isothermal Titration Calorimetry and Molecular Dynamics Studies.

PubMed

Tshabalala, Thabiso N; Tomescu, Mihai-Silviu; Prior, Allan; Balakrishnan, Vijayakumar; Sayed, Yasien; Dirr, Heini W; Achilonu, Ikechukwu

2016-12-01

The energetics of ligand binding to human eukaryotic elongation factor 1 gamma (heEF1γ) was investigated using reduced glutathione (GSH), oxidised glutathione (GSSG), glutathione sulfonate and S-hexylglutathione as ligands. The experiments were conducted using isothermal titration calorimetry, and the findings were supported using computational studies. The data show that the binding of these ligands to heEF1γ is enthalpically favourable and entropically driven (except for the binding of GSSG). The full length heEF1γ binds GSSG with lower affinity (K d  = 115 μM), with more hydrogen-bond contacts (ΔH = -73.8 kJ/mol) and unfavourable entropy (-TΔS = 51.7 kJ/mol) compared to the glutathione transferase-like N-terminus domain of heEF1γ, which did not show preference to any specific ligand. Computational free binding energy calculations from the 10 ligand poses show that GSSG and GSH consistently bind heEF1γ, and that both ligands bind at the same site with a folded bioactive conformation. This study reveals the possibility that heEF1γ is a glutathione-binding protein.

Competition effects in cation binding to humic acid: Conditional affinity spectra for fixed total metal concentration conditions

NASA Astrophysics Data System (ADS)

David, Calin; Mongin, Sandrine; Rey-Castro, Carlos; Galceran, Josep; Companys, Encarnació; Garcés, José Luis; Salvador, José; Puy, Jaume; Cecilia, Joan; Lodeiro, Pablo; Mas, Francesc

2010-09-01

Information on the Pb and Cd binding to a purified Aldrich humic acid (HA) is obtained from the influence of different fixed total metal concentrations on the acid-base titrations of this ligand. NICA (Non-Ideal Competitive Adsorption) isotherm has been used for a global quantitative description of the binding, which has then been interpreted by plotting the Conditional Affinity Spectra of the H + binding at fixed total metal concentrations (CAScTM). This new physicochemical tool, here introduced, allows the interpretation of binding results in terms of distributions of proton binding energies. A large increase in the acidity of the phenolic sites as the total metal concentration increases, especially in presence of Pb, is revealed from the shift of the CAScTM towards lower affinities. The variance of the CAScTM distribution, which can be used as a direct measure of the heterogeneity, also shows a significant dependence on the total metal concentration. A discussion of the factors that influence the heterogeneity of the HA under the conditions of each experiment is provided, so that the smoothed pattern exhibited by the titration curves can be justified.

Sensing of Double-Stranded DNA/RNA Secondary Structures by Water Soluble Homochiral Perylene Bisimide Dyes.

PubMed

Gershberg, Jana; Radić Stojković, Marijana; Škugor, Marko; Tomić, Sanja; Rehm, Thomas H; Rehm, Stefanie; Saha-Möller, Chantu R; Piantanida, Ivo; Würthner, Frank

2015-05-18

A broad series of homochiral perylene bisimide (PBI) dyes were synthesized that are appended with amino acids and cationic side chains at the imide positions. Self-assembly behavior of these ionic PBIs has been studied in aqueous media by UV/Vis spectroscopy, revealing formation of excitonically coupled H-type aggregates. The interactions of these ionic PBIs with different ds-DNA and ds-RNA have been explored by thermal denaturation, fluorimetric titration and circular dichroism (CD) experiments. These PBIs strongly stabilized ds-DNA/RNA against thermal denaturation as revealed by high melting temperatures of the formed PBI/polynucleotide complexes. Fluorimetric titrations showed that these PBIs bind to ds-DNA/RNA with high binding constants depending on the number of the positive charges in the side chains. Thus, spermine-containing PBIs with six positive charges each showed higher binding constants (logKs =9.2-9.8) than their dioxa analogues (logKs =6.5-7.9) having two positive charges each. Induced circular dichroism (ICD) of PBI assemblies created within DNA/RNA grooves was observed. These ICD profiles are strongly dependent on the steric demand of the chiral substituents of the amino acid units and the secondary structure of the DNA or RNA. The observed ICD effects can be explained by non-covalent binding of excitonically coupled PBI dimer aggregates into the minor groove of DNA and major groove of RNA which is further supported by molecular modeling studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kinetic and Thermodynamic Rationale for SAHA Being a Preferential Human HDAC8 Inhibitor as Compared to the Structurally Similar Ligand, TSA

PubMed Central

Singh, Raushan K.; Lall, Naveena; Leedahl, Travis S.; McGillivray, Abigail; Mandal, Tanmay; Haldar, Manas; Mallik, Sanku; Cook, Gregory; Srivastava, D.K.

2013-01-01

Of the different hydroxamate-based histone deacetylase (HDAC) inhibitors, Suberoylanilide hydroxamic acid (SAHA) has been approved by the FDA for treatment of T-cell lymphoma. Interestingly, a structurally similar inhibitor, Trichostatin A (TSA), which has a higher in vitro inhibitory-potency against HDAC8, reportedly shows a poor efficacy in clinical settings. In order to gain the molecular insight into the above discriminatory feature, we performed transient kinetic and isothermal titration calorimetric studies for the interaction of SAHA and TSA to the recombinant form of human HDAC8. The transient kinetic data revealed that the binding of both the inhibitors to the enzyme showed the biphasic profiles, which represented an initial encounter of enzyme with the inhibitor followed by the isomerization of the transient enzyme-inhibitor complexes. The temperature-dependent transient kinetic studies with the above inhibitors revealed that the bimolecular process is primarily dominated by favorable enthalpic changes, as opposed to the isomerization step; which is solely contributed by entropic changes. The standard binding-enthalpy (ΔH0) of SAHA, deduced from the transient kinetic as well as the isothermal titration calorimetric experiments, was 2–3 kcal/mol higher as compared to TSA. The experimental data presented herein suggests that SAHA serves as a preferential (target-specific/selective) HDAC8 inhibitor as compared to TSA. Arguments are presented that the detailed kinetic and thermodynamic studies may guide in the rational design of HDAC inhibitors as therapeutic agents. PMID:24079912

Colloidal characterization of ultrafine silicon carbide and silicon nitride powders

NASA Technical Reports Server (NTRS)

Whitman, Pamela K.; Feke, Donald L.

1986-01-01

The effects of various powder treatment strategies on the colloid chemistry of aqueous dispersions of silicon carbide and silicon nitride are examined using a surface titration methodology. Pretreatments are used to differentiate between the true surface chemistry of the powders and artifacts resulting from exposure history. Silicon nitride powders require more extensive pretreatment to reveal consistent surface chemistry than do silicon carbide powders. As measured by titration, the degree of proton adsorption from the suspending fluid by pretreated silicon nitride and silicon carbide powders can both be made similar to that of silica.

Evaluation of protein adsorption and preferred binding regions in multimodal chromatography using NMR

PubMed Central

Chung, Wai Keen; Freed, Alexander S.; Holstein, Melissa A.; McCallum, Scott A.; Cramer, Steven M.

2010-01-01

NMR titration experiments with labeled human ubiquitin were employed in concert with chromatographic data obtained with a library of ubiquitin mutants to study the nature of protein adsorption in multimodal (MM) chromatography. The elution order of the mutants on the MM resin was significantly different from that obtained by ion-exchange chromatography. Further, the chromatographic results with the protein library indicated that mutations in a defined region induced greater changes in protein affinity to the solid support. Chemical shift mapping and determination of dissociation constants from NMR titration experiments with the MM ligand and isotopically enriched ubiquitin were used to determine and rank the relative binding affinities of interaction sites on the protein surface. The results with NMR confirmed that the protein possessed a distinct preferred binding region for the MM ligand in agreement with the chromatographic results. Finally, coarse-grained ligand docking simulations were employed to study the modes of interaction between the MM ligand and ubiquitin. The use of NMR titration experiments in concert with chromatographic data obtained with protein libraries represents a previously undescribed approach for elucidating the structural basis of protein binding affinity in MM chromatographic systems. PMID:20837551

Interactive effects of dietary adaptation period length and titration diet type on apparent ileal phosphorus digestibility and phosphorus retention in growing broilers.

PubMed

Perryman, K R; Cattley, R C; Masey O'Neill, H V; Bedford, M R; Dozier, W A

2016-10-01

Two experiments were conducted to examine the effects of different corn titration diets and dietary adaptation period length (DAPL) on intestinal histology, apparent ileal P digestibility (AIPD), and apparent P retention (APR) in Ross × Ross 708 male broilers from 20 to 24 d of age. It was hypothesized that purified ingredients in nutrient-deficient titration diets may affect P availability with varying DAPL. In experiment 1, 1,152 broilers were utilized in a 3 × 3 factorial treatment structure with 3 diets (control, 25% corn titration diet [25CTD], or 75% corn titration diet [75CTD]) and 3 DAPL (0, 24, or 72 h). Experiment 2 was conducted with 576 broilers as a 4 × 3 factorial arrangement with 4 diets (control, 25CTD, 75CTD, or nitrogen-free diet [NFD]) and 3 DAPL (24, 48, or 72 h). All diets contained purified ingredients except for the control diet, which had the same formulation as the common starter and served as a control for DAPL. The NFD diet was fed as a highly purified protein-free diet. Broilers were fed a common diet until 19 d of age and then transferred to experimental diets at 20 d of age. In experiment 1, diet type did not affect (P > 0.05) intestinal histology. However, diet type and DAPL each influenced (P.≤.0.001) diet AIPD. Higher (P.≤.0.001) AIPD was measured for the control diet compared with the 75CDT, and the 25CTD had the lowest AIPD. Following a 24 h DAPL, AIPD was higher (P.≤.0.001) than after a DAPL of 0 or 72 h. In experiment 2, diet type × DAPL interactions (P.≤.0.001) were observed for APR of the control diet, 75CTD, and NFD, but not the 25CTD. Because APR of the control diet was affected by varying DAPL, factors other than differences in diet type may have been responsible for inconsistencies in the measure of P availability. Furthermore, no clear evidence was observed that broilers were able to adapt to P-deficient diets by increasing APR or AIPD. In conclusion, a standard DAPL should be established as a means to reduce variability associated with measuring of feedstuff P availability. © 2016 Poultry Science Association Inc.

Development and validation of a simplified titration method for monitoring volatile fatty acids in anaerobic digestion.

PubMed

Sun, Hao; Guo, Jianbin; Wu, Shubiao; Liu, Fang; Dong, Renjie

2017-09-01

The volatile fatty acids (VFAs) concentration has been considered as one of the most sensitive process performance indicators in anaerobic digestion (AD) process. However, the accurate determination of VFAs concentration in AD processes normally requires advanced equipment and complex pretreatment procedures. A simplified method with fewer sample pretreatment procedures and improved accuracy is greatly needed, particularly for on-site application. This report outlines improvements to the Nordmann method, one of the most popular titrations used for VFA monitoring. The influence of ion and solid interfering subsystems in titrated samples on results accuracy was discussed. The total solid content in titrated samples was the main factor affecting accuracy in VFA monitoring. Moreover, a high linear correlation was established between the total solids contents and VFA measurement differences between the traditional Nordmann equation and gas chromatography (GC). Accordingly, a simplified titration method was developed and validated using a semi-continuous experiment of chicken manure anaerobic digestion with various organic loading rates. The good fitting of the results obtained by this method in comparison with GC results strongly supported the potential application of this method to VFA monitoring. Copyright © 2017. Published by Elsevier Ltd.

Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

PubMed

Park, Jeong Bae; Shin, Joon-Han; Kim, Dong-Soo; Youn, Ho-Joong; Park, Seung Woo; Shim, Wan Joo; Park, Chang Gyu; Kim, Dong-Woon; Lee, Hae-Young; Choi, Dong-Ju; Rim, Se-Joong; Lee, Sung-Yun; Kim, Ju-Han

2016-04-01

Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Down-titration of biologics for the treatment of rheumatoid arthritis: a systematic literature review.

PubMed

Lau, Chak Sing; Gibofsky, Allan; Damjanov, Nemanja; Lula, Sadiq; Marshall, Lisa; Jones, Heather; Emery, Paul

2017-11-01

Biologic therapies have improved the management of rheumatoid arthritis (RA) and the treat-to-target approach has resulted in many patients achieving remission. In the current treatment landscape, clinicians have begun considering dose reduction/tapering for their patients. Rheumatology guidelines in Asia, Europe, and the United States include down-titration of biologics but admit that the level of evidence is moderate. We conducted a systematic literature review to assess the published studies that evaluate down-titration of biologics in RA. The published literature was searched for studies that down-titrated the following biologics: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Eligible studies included randomized controlled trials (RCTs), non-RCTs, observational, and pharmacoeconomic studies. The outcomes of interest were (1) efficacy and health-related quality of life, (2) disease flares, and (3) impact on cost. Eleven full-text publications were identified; only three were RCTs. Study results suggest that dosing down may be an option in many patients who have achieved remission or low disease activity. However, some patients are likely to experience a disease flare. Across the studies, the definition of disease flare and the down-titration criteria were inconsistent, making it difficult to conclude which patients may be appropriate and when to attempt down-titration. Studies have evaluated the practice of dosing down biologic therapy in patients with RA; however, a relatively small number of RCTs have been published. Although down-titration may be an option for some patients in LDA or remission, additional RCTs are needed to provide guidance on this practice.

Estimating the organic acid contribution to coastal seawater alkalinity by potentiometric titrations in a closed cell.

PubMed

Muller, François L L; Bleie, Bjørn

2008-07-07

This paper examines the performance of a previously reported, closed cell, potentiometric titration technique [J.M. Hernández-Ayón, S.L. Belli, A. Zirino, Anal. Chim. Acta 394 (1999) 101] for the simultaneous determination of pH, total inorganic carbon (TCO2), total alkalinity (TA), and organic alkalinity (OA) in coastal seawater samples. A novel interpretation of the titration data, as recently proposed by Hernández-Ayón et al. [J.M. Hernández-Ayón, A. Zirino, A.G. Dickson, T. Camiro-Vagas, E. Valenzuela-Espinoza, Limnol. Oceanogr.: Methods 5 (2007) 225] who applied it to waters of unusually high organic matter content, was applied here to fjord surface waters collected over the duration of a phytoplankton bloom. The parameters pH and TCO2--combined with knowledge of boric, phosphate and silicate species concentrations--allowed calculation of all inorganic species that contributed to TA. This inorganic alkalinity term was then subtracted from TA to produce an estimation of OA. Although the OA values obtained were very small (2-22+/-3 micromol L(-1)), they showed a reproducible trend over time in two simultaneous experiments. The organic acids that may have contributed to OA were characterised in back titrations of acidified and CO2-stripped samples with CO2-free NaOH. Two classes of organic titratable species, with pK(a) values around 4.0+/-0.2 and 9.1+/-0.2 were detected. The first occurred in concentrations that co-varied linearly (r2=0.75) with protein-like fluorescence, indicating a marine biological source, but were only weakly correlated (r2=0.46) to OA. By contrast, Class 2 organic species were not significantly correlated to any fluorescence component of either marine or terrestrial origin but were linearly correlated to OA (r2=0.69). These new results reveal that the method proposed by Hernández-Ayón et al. [J.M. Hernández-Ayón, A. Zirino, A.G. Dickson, T. Camiro-Vagas, E. Valenzuela-Espinoza, Limnol. Oceanogr.: Methods 5 (2007) 225] for estimating OA can provide a powerful and hitherto unused tool for analysing DOM dynamics and sources in most coastal environments, i.e. as a complement to the more widely used optical tools.

High-Resolution NMR Reveals Secondary Structure and Folding of Amino Acid Transporter from Outer Chloroplast Membrane

PubMed Central

Zook, James D.; Molugu, Trivikram R.; Jacobsen, Neil E.; Lin, Guangxin; Soll, Jürgen; Cherry, Brian R.; Brown, Michael F.; Fromme, Petra

2013-01-01

Solving high-resolution structures for membrane proteins continues to be a daunting challenge in the structural biology community. In this study we report our high-resolution NMR results for a transmembrane protein, outer envelope protein of molar mass 16 kDa (OEP16), an amino acid transporter from the outer membrane of chloroplasts. Three-dimensional, high-resolution NMR experiments on the 13C, 15N, 2H-triply-labeled protein were used to assign protein backbone resonances and to obtain secondary structure information. The results yield over 95% assignment of N, HN, CO, Cα, and Cβ chemical shifts, which is essential for obtaining a high resolution structure from NMR data. Chemical shift analysis from the assignment data reveals experimental evidence for the first time on the location of the secondary structure elements on a per residue basis. In addition T 1Z and T2 relaxation experiments were performed in order to better understand the protein dynamics. Arginine titration experiments yield an insight into the amino acid residues responsible for protein transporter function. The results provide the necessary basis for high-resolution structural determination of this important plant membrane protein. PMID:24205117

Solution structure of the C-terminal X domain of the measles virus phosphoprotein and interaction with the intrinsically disordered C-terminal domain of the nucleoprotein.

PubMed

Gely, Stéphane; Lowry, David F; Bernard, Cédric; Jensen, Malene R; Blackledge, Martin; Costanzo, Stéphanie; Bourhis, Jean-Marie; Darbon, Hervé; Daughdrill, Gary; Longhi, Sonia

2010-01-01

In this report, the solution structure of the nucleocapsid-binding domain of the measles virus phosphoprotein (XD, aa 459-507) is described. A dynamic description of the interaction between XD and the disordered C-terminal domain of the nucleocapsid protein, (N(TAIL), aa 401-525), is also presented. XD is an all alpha protein consisting of a three-helix bundle with an up-down-up arrangement of the helices. The solution structure of XD is very similar to the crystal structures of both the free and bound form of XD. One exception is the presence of a highly dynamic loop encompassing XD residues 489-491, which is involved in the embedding of the alpha-helical XD-binding region of N(TAIL). Secondary chemical shift values for full-length N(TAIL) were used to define the precise boundaries of a transient helical segment that coincides with the XD-binding domain, thus shedding light on the pre-recognition state of N(TAIL). Titration experiments with unlabeled XD showed that the transient alpha-helical conformation of N(TAIL) is stabilized upon binding. Lineshape analysis of NMR resonances revealed that residues 483-506 of N(TAIL) are in intermediate exchange with XD, while the 475-482 and 507-525 regions are in fast exchange. The N(TAIL) resonance behavior in the titration experiments is consistent with a complex binding model with more than two states.

Protein NMR Studies of Substrate Binding to Human Blood Group A and B Glycosyltransferases.

PubMed

Grimm, Lena Lisbeth; Weissbach, Sophie; Flügge, Friedemann; Begemann, Nora; Palcic, Monica M; Peters, Thomas

2017-07-04

Donor and acceptor substrate binding to human blood group A and B glycosyltransferases (GTA, GTB) has been studied by a variety of protein NMR experiments. Prior crystallographic studies had shown these enzymes to adopt an open conformation in the absence of substrates. Binding either of the donor substrate UDP-Gal or of UDP induces a semiclosed conformation. In the presence of both donor and acceptor substrates, the enzymes shift towards a closed conformation with ordering of an internal loop and the C-terminal residues, which then completely cover the donor-binding pocket. Chemical-shift titrations of uniformly 2 H, 15 N-labeled GTA or GTB with UDP affected about 20 % of all crosspeaks in 1 H, 15 N TROSY-HSQC spectra, reflecting substantial plasticity of the enzymes. On the other hand, it is this conformational flexibility that impedes NH backbone assignments. Chemical-shift-perturbation experiments with δ1-[ 13 C]methyl-Ile-labeled samples revealed two Ile residues-Ile123 at the bottom of the UDP binding pocket, and Ile192 as part of the internal loop-that were significantly disturbed upon stepwise addition of UDP and H-disaccharide, also revealing long-range perturbations. Finally, methyl TROSY-based relaxation dispersion experiments do not reveal micro- to millisecond timescale motions. Although this study reveals substantial conformational plasticity of GTA and GTB, the matter of how binding of substrates shifts the enzymes into catalytically competent states remains enigmatic. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Binding of warfarin influences the acid-base equilibrium of H242 in sudlow site I of human serum albumin.

PubMed

Perry, Jennifer L; Goldsmith, Michael R; Williams, T Richard; Radack, Kyle P; Christensen, Trine; Gorham, Justin; Pasquinelli, Melissa A; Toone, Eric J; Beratan, David N; Simon, John D

2006-01-01

Sudlow Site I of human serum albumin (HSA) is located in subdomain IIA of the protein and serves as a binding cavity for a variety of ligands. In this study, the binding of warfarin (W) is examined using computational techniques and isothermal titration calorimetry (ITC). The structure of the docked warfarin anion (W-) to Site I is similar to that revealed by X-ray crystallography, with a calculated binding constant of 5.8 x 10(5) M(-1). ITC experiments (pH 7.13 and I = 0.1) carried out in three different buffers (MOPs, phosphate and Tris) reveal binding of W- is accompanied by uptake of 0.30+/-0.02 protons from the solvent. This measurement suggests that the binding of W- is stabilized by an ion-pair interaction between protonated H242 and the phenoxide group of W-.

Isothermal titration calorimetry for measuring macromolecule-ligand affinity.

PubMed

Duff, Michael R; Grubbs, Jordan; Howell, Elizabeth E

2011-09-07

Isothermal titration calorimetry (ITC) is a useful tool for understanding the complete thermodynamic picture of a binding reaction. In biological sciences, macromolecular interactions are essential in understanding the machinery of the cell. Experimental conditions, such as buffer and temperature, can be tailored to the particular binding system being studied. However, careful planning is needed since certain ligand and macromolecule concentration ranges are necessary to obtain useful data. Concentrations of the macromolecule and ligand need to be accurately determined for reliable results. Care also needs to be taken when preparing the samples as impurities can significantly affect the experiment. When ITC experiments, along with controls, are performed properly, useful binding information, such as the stoichiometry, affinity and enthalpy, are obtained. By running additional experiments under different buffer or temperature conditions, more detailed information can be obtained about the system. A protocol for the basic setup of an ITC experiment is given.

Isothermal Titration Calorimetry for Measuring Macromolecule-Ligand Affinity

PubMed Central

Duff,, Michael R.; Grubbs, Jordan; Howell, Elizabeth E.

2011-01-01

Isothermal titration calorimetry (ITC) is a useful tool for understanding the complete thermodynamic picture of a binding reaction. In biological sciences, macromolecular interactions are essential in understanding the machinery of the cell. Experimental conditions, such as buffer and temperature, can be tailored to the particular binding system being studied. However, careful planning is needed since certain ligand and macromolecule concentration ranges are necessary to obtain useful data. Concentrations of the macromolecule and ligand need to be accurately determined for reliable results. Care also needs to be taken when preparing the samples as impurities can significantly affect the experiment. When ITC experiments, along with controls, are performed properly, useful binding information, such as the stoichiometry, affinity and enthalpy, are obtained. By running additional experiments under different buffer or temperature conditions, more detailed information can be obtained about the system. A protocol for the basic setup of an ITC experiment is given. PMID:21931288

Modified spectrophotometer for multi-dimensional circular dichroism/fluorescence data acquisition in titration experiments: application to the pH and guanidine-HCI induced unfolding of apomyoglobin.

PubMed

Ramsay, G; Ionescu, R; Eftink, M R

1995-08-01

In a previous paper (Ramsay and Eftink, Biophys. J. 66:516-523) we reported the development of a modified spectrophotometer that can make nearly simultaneous circular dichroism (CD) and fluorescence measurements. This arrangement allows multiple data sets to be collected during a single experiment, resulting in a saving of time and material, and improved correlation between the different types of measurements. The usefulness of the instrument was shown by thermal melting experiments on several different protein systems. This CD/fluorometer spectrophotometer has been further modified by interfacing with a syringe pump and a pH meter. This arrangement allows ligand, pH, and chemical denaturation titration experiments to be performed while monitoring changes in the sample's CD, absorbance, fluorescence, and light scattering properties. Our data acquisition program also has an ability to check whether the signals have approached equilibrium before the data is recorded. For performing pH titrations we have developed a procedure which uses the signal from a pH meter in a feedback circuit in order to collect data at evenly spaced pH intervals. We demonstrate the use of this instrument with studies of the unfolding of sperm whale apomyoglobin, as induced by acid pH and by the addition of guanidine-HCI.

Modified spectrophotometer for multi-dimensional circular dichroism/fluorescence data acquisition in titration experiments: application to the pH and guanidine-HCI induced unfolding of apomyoglobin.

PubMed Central

Ramsay, G; Ionescu, R; Eftink, M R

1995-01-01

In a previous paper (Ramsay and Eftink, Biophys. J. 66:516-523) we reported the development of a modified spectrophotometer that can make nearly simultaneous circular dichroism (CD) and fluorescence measurements. This arrangement allows multiple data sets to be collected during a single experiment, resulting in a saving of time and material, and improved correlation between the different types of measurements. The usefulness of the instrument was shown by thermal melting experiments on several different protein systems. This CD/fluorometer spectrophotometer has been further modified by interfacing with a syringe pump and a pH meter. This arrangement allows ligand, pH, and chemical denaturation titration experiments to be performed while monitoring changes in the sample's CD, absorbance, fluorescence, and light scattering properties. Our data acquisition program also has an ability to check whether the signals have approached equilibrium before the data is recorded. For performing pH titrations we have developed a procedure which uses the signal from a pH meter in a feedback circuit in order to collect data at evenly spaced pH intervals. We demonstrate the use of this instrument with studies of the unfolding of sperm whale apomyoglobin, as induced by acid pH and by the addition of guanidine-HCI. Images FIGURE 2 PMID:8527683

Predicting prolonged dose titration in patients starting warfarin.

PubMed

Finkelman, Brian S; French, Benjamin; Bershaw, Luanne; Brensinger, Colleen M; Streiff, Michael B; Epstein, Andrew E; Kimmel, Stephen E

2016-11-01

Patients initiating warfarin therapy generally experience a dose-titration period of weeks to months, during which time they are at higher risk of both thromboembolic and bleeding events. Accurate prediction of prolonged dose titration could help clinicians determine which patients might be better treated by alternative anticoagulants that, while more costly, do not require dose titration. A prediction model was derived in a prospective cohort of patients starting warfarin (n = 390), using Cox regression, and validated in an external cohort (n = 663) from a later time period. Prolonged dose titration was defined as a dose-titration period >12 weeks. Predictor variables were selected using a modified best subsets algorithm, using leave-one-out cross-validation to reduce overfitting. The final model had five variables: warfarin indication, insurance status, number of doctor's visits in the previous year, smoking status, and heart failure. The area under the ROC curve (AUC) in the derivation cohort was 0.66 (95%CI 0.60, 0.74) using leave-one-out cross-validation, but only 0.59 (95%CI 0.54, 0.64) in the external validation cohort, and varied across clinics. Including genetic factors in the model did not improve the area under the ROC curve (0.59; 95%CI 0.54, 0.65). Relative utility curves indicated that the model was unlikely to provide a clinically meaningful benefit compared with no prediction. Our results suggest that prolonged dose titration cannot be accurately predicted in warfarin patients using traditional clinical, social, and genetic predictors, and that accurate prediction will need to accommodate heterogeneities across clinical sites and over time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

pytc: Open-Source Python Software for Global Analyses of Isothermal Titration Calorimetry Data.

PubMed

Duvvuri, Hiranmayi; Wheeler, Lucas C; Harms, Michael J

2018-05-08

Here we describe pytc, an open-source Python package for global fits of thermodynamic models to multiple isothermal titration calorimetry experiments. Key features include simplicity, the ability to implement new thermodynamic models, a robust maximum likelihood fitter, a fast Bayesian Markov-Chain Monte Carlo sampler, rigorous implementation, extensive documentation, and full cross-platform compatibility. pytc fitting can be done using an application program interface or via a graphical user interface. It is available for download at https://github.com/harmslab/pytc .

Toward accurate prediction of pKa values for internal protein residues: the importance of conformational relaxation and desolvation energy.

PubMed

Wallace, Jason A; Wang, Yuhang; Shi, Chuanyin; Pastoor, Kevin J; Nguyen, Bao-Linh; Xia, Kai; Shen, Jana K

2011-12-01

Proton uptake or release controls many important biological processes, such as energy transduction, virus replication, and catalysis. Accurate pK(a) prediction informs about proton pathways, thereby revealing detailed acid-base mechanisms. Physics-based methods in the framework of molecular dynamics simulations not only offer pK(a) predictions but also inform about the physical origins of pK(a) shifts and provide details of ionization-induced conformational relaxation and large-scale transitions. One such method is the recently developed continuous constant pH molecular dynamics (CPHMD) method, which has been shown to be an accurate and robust pK(a) prediction tool for naturally occurring titratable residues. To further examine the accuracy and limitations of CPHMD, we blindly predicted the pK(a) values for 87 titratable residues introduced in various hydrophobic regions of staphylococcal nuclease and variants. The predictions gave a root-mean-square deviation of 1.69 pK units from experiment, and there were only two pK(a)'s with errors greater than 3.5 pK units. Analysis of the conformational fluctuation of titrating side-chains in the context of the errors of calculated pK(a) values indicate that explicit treatment of conformational flexibility and the associated dielectric relaxation gives CPHMD a distinct advantage. Analysis of the sources of errors suggests that more accurate pK(a) predictions can be obtained for the most deeply buried residues by improving the accuracy in calculating desolvation energies. Furthermore, it is found that the generalized Born implicit-solvent model underlying the current CPHMD implementation slightly distorts the local conformational environment such that the inclusion of an explicit-solvent representation may offer improvement of accuracy. Copyright © 2011 Wiley-Liss, Inc.

Determinations of Carbon Dioxide by Titration: New Experiments for General, Physical, and Quantitative Analysis Courses.

ERIC Educational Resources Information Center

Crossno, S. K.; And Others

1996-01-01

Presents experiments involving the analysis of commercial products such as carbonated beverages and antacids that illustrate the principles of acid-base reactions and present interesting problems in stoichiometry for students. (JRH)

Probing the recognition surface of a DNA triplex: binding studies with intercalator-neomycin conjugates.

PubMed

Xue, Liang; Xi, Hongjuan; Kumar, Sunil; Gray, David; Davis, Erik; Hamilton, Paris; Skriba, Michael; Arya, Dev P

2010-07-06

Thermodynamic studies on the interactions between intercalator-neomycin conjugates and a DNA polynucleotide triplex [poly(dA).2poly(dT)] were conducted. To draw a complete picture of such interactions, naphthalene diimide-neomycin (3) and anthraquinone-neomycin (4) conjugates were synthesized and used together with two other analogues, previously synthesized pyrene-neomycin (1) and BQQ-neomycin (2) conjugates, in our investigations. A combination of experiments, including UV denaturation, circular dichroism (CD) titration, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC), revealed that all four conjugates (1-4) stabilized poly(dA).2poly(dT) much more than its parent compound, neomycin. UV melting experiments clearly showed that the temperature (T(m3-->2)) at which poly(dA).2poly(dT) dissociated into poly(dA).poly(dT) and poly(dT) increased dramatically (>12 degrees C) in the presence of intercalator-neomycin conjugates (1-4) even at a very low concentration (2 muM). In contrast to intercalator-neomycin conjugates, the increment of T(m3-->2) of poly(dA).2poly(dT) induced by neomycin was negligible under the same conditions. The binding preference of intercalator-neomycin conjugates (1-4) to poly(dA).2poly(dT) was also confirmed by competition dialysis and a fluorescent intercalator displacement assay. Circular dichroism titration studies revealed that compounds 1-4 had slightly larger binding site size ( approximately 7-7.5) with poly(dA).2poly(dT) as compared to neomycin ( approximately 6.5). The thermodynamic parameters of these intercalator-neomycin conjugates with poly(dA).2poly(dT) were derived from an integrated van't Hoff equation using the T(m3-->2) values, the binding site size numbers, and other parameters obtained from DSC and ITC. The binding affinity of all tested ligands with poly(dA).2poly(dT) increased in the following order: neomycin < 1 < 3 < 4 < 2. Among them, the binding constant [(2.7 +/- 0.3) x 10(8) M(-1)] of 2 with poly(dA).2poly(dT) was the highest, almost 1000-fold greater than that of neomycin. The binding of compounds 1-4 with poly(dA).2poly(dT) was mostly enthalpy-driven and gave negative DeltaC(p) values. The results described here suggest that the binding affinity of intercalator-neomycin conjugates for poly(dA).2poly(dT) increases as a function of the surface area of the intercalator moiety.

Surface-Bound Intermediates in Low-Temperature Methanol Synthesis on Copper. Participants and Spectators

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

Yang, Yong; Mei, Donghai; Peden, Charles H.F.

The reactivity of surface adsorbed species present on copper catalysts during methanol synthesis at low temperatures was studied by simultaneous infrared spectroscopy (IR) and mass spectroscopy (MS) measurements during “titration” (transient surface reaction) experiments with isotopic tracing. The results show that adsorbed formate is a major bystander species present on the surface under steady-state methanol synthesis reaction conditions, but it cannot be converted to methanol by reaction with pure H 2, nor with H 2 plus added water. Formate-containing surface adlayers for these experiments were produced during steady state catalysis in (a) H 2:CO 2 (with substantial formate coverage) andmore » (b) moist H 2:CO (with no IR visible formate species). Both these reaction conditions produce methanol at steady state with relatively high rates. Adlayers containing formate were also produced by (c) formic acid adsorption. Various "titration" gases were used to probe these adlayers at modest temperatures (T = 410-450K) and 6 bar total pressure. Methanol gas (up to ~1% monolayer equivalent) was produced in "titration" from the H 2:CO 2 catalytic adlayers by H 2 plus water, but not by dry hydrogen. The decay in the formate IR features accelerated in the presence of added water vapor. The H 2:CO:H 2O catalytic adlayer produced similar methanol titration yields in H 2 plus water but showed no surface formate features in IR (less than 0.2% monolayer coverage). Finally, formate from formic acid chemisorption produced no methanol under any titration conditions. Even under (H 2:CO 2) catalytic reaction conditions, isotope tracing showed that pre-adsorbed formate from formic acid did not contribute to the methanol produced. Although non-formate intermediates exist during low temperature methanol synthesis on copper which can be converted to methanol gas by titration with pure H 2 plus water in sufficient quantities for that intermediate to be observable by IR, formate itself is only a "spectator" in this reaction and gives no observable methanol upon any titration we performed with H 2 or H 2 plus water.« less

Thermodynamic analysis of Bacillus subtilis endospore protonation using isothermal titration calorimetry

NASA Astrophysics Data System (ADS)

Harrold, Zoë R.; Gorman-Lewis, Drew

2013-05-01

Bacterial proton and metal adsorption reactions have the capacity to affect metal speciation and transport in aqueous environments. We coupled potentiometric titration and isothermal titration calorimetry (ITC) analyses to study Bacillus subtilis spore-proton adsorption. We modeled the potentiometric data using a four and five-site non-electrostatic surface complexation model (NE-SCM). Heats of spore surface protonation from coupled ITC analyses were used to determine site specific enthalpies of protonation based on NE-SCMs. The five-site model resulted in a substantially better model fit for the heats of protonation but did not significantly improve the potentiometric titration model fit. The improvement observed in the five-site protonation heat model suggests the presence of a highly exothermic protonation reaction circa pH 7 that cannot be resolved in the less sensitive potentiometric data. From the log Ks and enthalpies we calculated corresponding site specific entropies. Log Ks and site concentrations describing spore surface protonation are statistically equivalent to B. subtilis cell surface protonation constants. Spore surface protonation enthalpies, however, are more exothermic relative to cell based adsorption suggesting a different bonding environment. The thermodynamic parameters defined in this study provide insight on molecular scale spore-surface protonation reactions. Coupled ITC and potentiometric titrations can reveal highly exothermic, and possibly endothermic, adsorption reactions that are overshadowed in potentiometric models alone. Spore-proton adsorption NE-SCMs derived in this study provide a framework for future metal adsorption studies.

Effect of dissolved oxygen on two bacterial pathogens examined using ATR-FTIR spectroscopy, microelectrophoresis, and potentiometric titration.

PubMed

Castro, Felipe D; Sedman, Jacqueline; Ismail, Ashraf A; Asadishad, Bahareh; Tufenkji, Nathalie

2010-06-01

The effects of dissolved oxygen tension during bacterial growth and acclimation on the cell surface properties and biochemical composition of the bacterial pathogens Escherichia coli O157:H7 and Yersinia enterocolitica are characterized. Three experimental techniques are used in an effort to understand the influence of bacterial growth and acclimation conditions on cell surface charge and the composition of the bacterial cell: (i) electrophoretic mobility measurements; (ii) potentiometric titration; and (iii) ATR-FTIR spectroscopy. Potentiometric titration data analyzed using chemical speciation software are related to measured electrophoretic mobilities at the pH of interest. Titration of bacterial cells is used to identify the major proton-active functional groups and the overall concentration of these cell surface ligands at the cell membrane. Analysis of titration data shows notable differences between strains and conditions, confirming the appropriateness of this tool for an overall charge characterization. ATR-FTIR spectroscopy of whole cells is used to further characterize the bacterial biochemical composition and macromolecular structures that might be involved in the development of the net surficial charge of the organisms examined. The evaluation of the integrated intensities of HPO(2)(-) and carbohydrate absorption bands in the IR spectra reveals clear differences between growth protocols. Taken together, the three techniques seem to indicate that the dissolved oxygen tension during cell growth or acclimation can noticeably influence the expression of cell surface molecules and the measurable cell surface charge, though in a strain-dependent fashion.

Microcalorimetric and potentiometric titration studies on the adsorption of copper by extracellular polymeric substances (EPS), minerals and their composites.

PubMed

Fang, Linchuan; Huang, Qiaoyun; Wei, Xing; Liang, Wei; Rong, Xinming; Chen, Wenli; Cai, Peng

2010-08-01

Equilibrium adsorption experiments, isothermal titration calorimetry and potentiometric titration techniques were employed to investigate the adsorption of Cu(II) by extracellular polymeric substances (EPS) extracted from Pseudomonas putida X4, minerals (montmorillonite and goethite) and their composites. Compared with predicted values of Cu(II) adsorption on composites, the measured values of Cu(II) on EPS-montmorillonite composite increased, however, those on EPS-goethite composite decreased. Potentiometric titration results also showed that more surface sites were observed on EPS-montmorillonite composite and less reactive sites were found on EPS-goethite composite. The adsorption of Cu(II) on EPS molecules and their composites with minerals was an endothermic reaction, while that on minerals was exothermic. The positive values of enthalpy change (Delta H) and entropy change (DeltaS) for Cu(II) adsorption on EPS and mineral-EPS composites indicated that Cu(II) mainly interacts with carboxyl and phosphoryl groups as inner-sphere complexes on EPS molecules and their composites with minerals. (c) 2010 Elsevier Ltd. All rights reserved.

Chelerythrine down regulates expression of VEGFA, BCL2 and KRAS by arresting G-Quadruplex structures at their promoter regions.

PubMed

Jana, Jagannath; Mondal, Soma; Bhattacharjee, Payel; Sengupta, Pallabi; Roychowdhury, Tanaya; Saha, Pranay; Kundu, Pallob; Chatterjee, Subhrangsu

2017-01-19

A putative anticancer plant alkaloid, Chelerythrine binds to G-quadruplexes at promoters of VEGFA, BCL2 and KRAS genes and down regulates their expression. The association of Chelerythrine to G-quadruplex at the promoters of these oncogenes were monitored using UV absorption spectroscopy, fluorescence anisotropy, circular dichroism spectroscopy, CD melting, isothermal titration calorimetry, molecular dynamics simulation and quantitative RT-PCR technique. The pronounced hypochromism accompanied by red shifts in UV absorption spectroscopy in conjunction with ethidium bromide displacement assay indicates end stacking mode of interaction of Chelerythrine with the corresponding G-quadruplex structures. An increase in fluorescence anisotropy and CD melting temperature of Chelerythrine-quadruplex complex revealed the formation of stable Chelerythrine-quadruplex complex. Isothermal titration calorimetry data confirmed that Chelerythrine-quadruplex complex formation is thermodynamically favourable. Results of quantative RT-PCR experiment in combination with luciferase assay showed that Chelerythrine treatment to MCF7 breast cancer cells effectively down regulated transcript level of all three genes, suggesting that Chelerythrine efficiently binds to in cellulo quadruplex motifs. MD simulation provides the molecular picture showing interaction between Chelerythrine and G-quadruplex. Binding of Chelerythrine with BCL2, VEGFA and KRAS genes involved in evasion, angiogenesis and self sufficiency of cancer cells provides a new insight for the development of future therapeutics against cancer.

Pb(II) adsorption by biomass from chemically modified aquatic macrophytes, Salvinia sp. and Pistia stratiotes.

PubMed

de Moraes Ferreira, Rachel; de Souza, Michael Douglas Peçanha; Takase, Iracema; de Araujo Stapelfeldt, Danielle Marques

2016-01-01

This study used two biosorbents obtained from the aquatic plants Salvinia sp. and Pistia stratiotes to establish a sustainable and alternative treatment for industrial wastewater and other water bodies that contain Pb(II). The biosorbent named Salvinia with NaOH (SOH) was obtained from Salvinia sp., and Salvinia and Pistia mixture with NaOH (SPOH) was obtained from a mixture of the two plants in a 1:1 ratio. The biosorbents were characterized by zeta potential, infrared (IR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive spectroscopy and Boehm titration. The results of Boehm titration and IR analysis indicated the presence of basic functional groups, whereas those of SEM analysis indicated that the biosorbents have a structure conducive to adsorption. Batch adsorption experiments were performed to observe the effects of pH, contact time, initial lead concentration and temperature on the metal removal process. The results revealed that the biosorbents efficiently removed Pb(II) from aqueous solutions, with a maximum observed adsorption capacity (saturation limits, qmax) of 202 mg g(-1) and 210.1 mg g(-1) for SPOH and SOH, respectively. The Freundlich, Langmuir and Dubinin-Radushkevich models were applied to the data; these biosorbent studies did not satisfactorily adjust to either of the models, but the information obtained helped us understand the adsorption mechanism.

Chelerythrine down regulates expression of VEGFA, BCL2 and KRAS by arresting G-Quadruplex structures at their promoter regions

NASA Astrophysics Data System (ADS)

Jana, Jagannath; Mondal, Soma; Bhattacharjee, Payel; Sengupta, Pallabi; Roychowdhury, Tanaya; Saha, Pranay; Kundu, Pallob; Chatterjee, Subhrangsu

2017-01-01

A putative anticancer plant alkaloid, Chelerythrine binds to G-quadruplexes at promoters of VEGFA, BCL2 and KRAS genes and down regulates their expression. The association of Chelerythrine to G-quadruplex at the promoters of these oncogenes were monitored using UV absorption spectroscopy, fluorescence anisotropy, circular dichroism spectroscopy, CD melting, isothermal titration calorimetry, molecular dynamics simulation and quantitative RT-PCR technique. The pronounced hypochromism accompanied by red shifts in UV absorption spectroscopy in conjunction with ethidium bromide displacement assay indicates end stacking mode of interaction of Chelerythrine with the corresponding G-quadruplex structures. An increase in fluorescence anisotropy and CD melting temperature of Chelerythrine-quadruplex complex revealed the formation of stable Chelerythrine-quadruplex complex. Isothermal titration calorimetry data confirmed that Chelerythrine-quadruplex complex formation is thermodynamically favourable. Results of quantative RT-PCR experiment in combination with luciferase assay showed that Chelerythrine treatment to MCF7 breast cancer cells effectively down regulated transcript level of all three genes, suggesting that Chelerythrine efficiently binds to in cellulo quadruplex motifs. MD simulation provides the molecular picture showing interaction between Chelerythrine and G-quadruplex. Binding of Chelerythrine with BCL2, VEGFA and KRAS genes involved in evasion, angiogenesis and self sufficiency of cancer cells provides a new insight for the development of future therapeutics against cancer.

Non-intercalative, deoxyribose binding of boric acid to calf thymus DNA.

PubMed

Ozdemir, Ayse; Gursaclı, Refiye Tekiner; Tekinay, Turgay

2014-05-01

The present study characterizes the effects of the boric acid binding on calf thymus DNA (ct-DNA) by spectroscopic and calorimetric methods. UV-Vis absorbance spectroscopy, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and Fourier transform infrared (FT-IR) spectroscopy were employed to characterize binding properties. Changes in the secondary structure of ct-DNA were determined by CD spectroscopy. Sizes and morphologies of boric acid-DNA complexes were determined by transmission electron microscopy (TEM). The kinetics of boric acid binding to calf thymus DNA (ct-DNA) was investigated by isothermal titration calorimetry (ITC). ITC results revealed that boric acid exhibits a moderate affinity to ct-DNA with a binding constant (K a) of 9.54 × 10(4) M(-1). FT-IR results revealed that boric acid binds to the deoxyribose sugar of DNA without disrupting the B-conformation at tested concentrations.

Humic substance charge determination by titration with a flexible cationic polyelectrolyte

NASA Astrophysics Data System (ADS)

Tan, Wen-Feng; Norde, Willem; Koopal, Luuk K.

2011-10-01

The anionic charge of humic substances (HS) plays a major role in the interaction of HS with other components. Therefore, the potential of the polyelectrolyte titration technique to obtain the charge density of HS in simple 1-1 electrolyte solutions has been investigated. Titrations are carried out with an automatic titrator combined with the "Mütek particle charge detector" which allows determination of the Mütek potential and the pH as a function of the added amount of titrant which is a solution of poly-diallyldimethylammonium chloride (polyDADMAC), a cationic strong polyelectrolyte. When the Mütek potential reverses its sign the iso-electric point (IEP) of the polyDADMAC-HS complex is reached. The polyDADMAC/HS mass ratio at the IEP gives information on the HS charge density and from the pH changes in solution an estimate of the charge regulation in the HS-polyDADMAC complex can be obtained. In general, for polyDADMAC-HS complexes an increase in the dissociation of the acid groups of HS is found (charge regulation). The charge regulation decreases with increasing concentration of 1-1 background electrolyte. Cation incorporation can be neglected at 1-1 electrolyte concentrations ⩽ 1 mmol L -1 and a 1-1 stoichiometry exists between the polyDADMAC and HS charge. However, at these low salt concentrations the charge regulation is substantial. A detailed analysis of purified Aldrich humic acid (PAHA) at pH 5 and a range of KCl concentrations reveals that the anionic charge of PAHA in the complex increases at 5 mmol L -1 KCl by 30% and at 150 mmol L -1 KCl by 12%. On the other hand, increasing amounts of K + become incorporated in the complex: at 5 mmol L -1 KCl 5% and at 150 mmol L -1 KCl 24% of the PAHA charge is balanced by K +. By comparing at pH 5 the mass ratios polyDADMAC/PAHA in the complex at the IEP with the theoretical mass ratios of polyDADMAC/PAHA required to neutralize PAHA in the absence of charge regulation and K + incorporation, it is found that at 50 mmol L -1 KCl the extra negative charge due to the interaction between polyDADMAC and PAHA is just compensated by K + incorporation in the complex. Therefore, a pseudo 1-1 stoichiometry exists at about 50 mmol L -1 1-1 electrolyte concentration and only at this salt concentration polyDADMAC titrations and conventional proton titrations give identical results. Most likely this is also true for other HA samples and other pH values. For FA further study is required to reveal the conditions for which polyDADMAC and proton titrations give identical results.

Theoretical and experimental study of organic nano-material for acetate anion based on 1, 10-phenanthroline.

PubMed

Shang, Xuefang; Zhao, Yuan; Wei, Xiaofang; Feng, Yaqian; Li, Xin; Gao, Shuyan; Xu, Xiufang

2015-01-01

New phenanthroline derivatives (1, 2, 3, 4) containing phenol groups have been synthesized and optimized. The nano-material of compound 2 was also developed. Their binding properties were evaluated for various biological anions (F(-), Cl(-), Br(-), I(-), AcO(-) and H(2)PO(4)(-)) by theoretical investigation, UV-vis, fluorescence, (1)HNMR titration experiments and these compounds all showed strong binding ability for AcO(-) without the interference of other anions tested. The anion binding ability could be regularized by electron push-pull properties of the ortho- or para- substituent on benzene. Theoretical investigation analysis revealed the effect of intramolecular hydrogen bond existed between -OH and other atoms in the structure of these compounds.

Chemistry Notes

ERIC Educational Resources Information Center

Pinkney, J. N.; And Others

1976-01-01

Describes eleven laboratory experiments, including the catalytic effect of copper in zinc-acid reaction; a study of the rate of polymerization of some aldehydes; and a demonstration automatic potentiometric titrator. (MLH)

Field and In-Lab Determination of Ca[superscript 2+] in Seawater

ERIC Educational Resources Information Center

Stoodley, Robin; Nun~ez, Jose R. Rodriguez; Bartz, Tessa

2014-01-01

Portions of classic undergraduate quantitative analysis experiments in complexiometric titration and potentiometry are combined with a field-sampling experience to create a two period (2 × 3 h) comparison-based experiment for second-year students. A multifunctional chemical analysis device is used with calcium ion-selective electrode for field…

Sensitivity of the acid-base properties of clays to the methods of preparation and measurement. 2. Evidence from continuous potentiometric titrations.

PubMed

Duc, Myriam; Gaboriaud, Fabien; Thomas, Fabien

2005-09-01

The effects of experimental procedures on the acid-base consumption titration curves of montmorillonite suspension were studied using continuous potentiometric titration. For that purpose, the hysteresis amplitudes between the acid and base branches were found to be useful to systematically evaluate the impacts of storage conditions (wet or dried), the atmosphere in titration reactor, the solid-liquid ratio, the time interval between successive increments, and the ionic strength. In the case of storage conditions, the increase of the hysteresis was significantly higher for longer storage of clay in suspension and drying procedures compared to "fresh" clay suspension. The titration carried out under air demonstrated carbonate contamination that could only be cancelled by performing experiments under inert gas. Interestingly, the increase of the time intervals between successive increments of titrant strongly emphasized the amplitude of hysteresis, which could be correlated with the slow kinetic process specifically observed for acid addition in acid media. Thus, such kinetic behavior is probably associated with dissolution processes of clay particles. However, the resulting curves recorded at different ionic strengths under optimized conditions did not show the common intersection point required to define point of zero charge. Nevertheless, the ionic strength dependence of the point of zero net proton charge suggested that the point of zero charge of sodic montmorillonite could be estimated as lower than 5.

Change in frequency of periodic limb movements during sleep with usage of continuous positive airway pressure in obstructive sleep apnea syndrome.

PubMed

Aritake-Okada, Sayaka; Namba, Kazuyoshi; Hidano, Natsuki; Asaoka, Shoichi; Komada, Yoko; Usui, Akira; Matsuura, Masato; Inoue, Yuichi

2012-06-15

Periodic limb movements during sleep (PLMS) sometimes newly appear on the night of continuous positive airway pressure (CPAP) titration in patients with obstructive sleep apnea syndrome (OSAS). To ascertain the incidence and causative factors of this phenomenon, we investigated differences in its prevalence and the factors associated with newly appeared and persistent PLMS on CPAP titration night. We retrospectively analyzed polysomnographic data of 997 consecutive OSAS outpatients who had undergone overnight CPAP titration. On the basis of changes in periodic limb movements index (PLMI) values (cut off level≥15/h) from baseline polysomnography (BPSG) to CPAP titration PSG, patients were assigned to one of four groups: persistent, CPAP-emergent, CPAP-disappeared, and non-PLMS. The rate of patients was 6.7% in the persistent group, 8.0% in the CPAP-emergent group, 4.0% in the CPAP-disappearance group, and 81.2% in the non-PLMS group. Multivariate logistic regression analysis revealed that a higher apnea-hypopnea index (AHI) on BPSG and ≥47years of age appeared to be associated with the CPAP-emergent group. The results suggest that elderly patients with higher AHI at BPSG may present with CPAP-emergent PLMS. Copyright © 2012. Published by Elsevier B.V.

Calorimetry, activity, and micro-FTIR analysis of CO chemisorption, titration, and oxidation on supported Pt

NASA Technical Reports Server (NTRS)

Sermon, Paul A.; Self, Valerie A.; Vong, Mariana S. W.; Wurie, Alpha T.

1990-01-01

The value of in situ analysis on CO chemisorption, titration and oxidation over supported Pt catalysts using calorimetry, catalytic and micro-FTIR methods is illustrated using silica- and titania-supported samples. Isothermal CO-O and O2-CO titrations have not been widely used on metal surfaces and may be complicated if some oxide supports are reduced by CO titrant. However, they can illuminate the kinetics of CO oxidation on metal/oxide catalysts since during such titrations all O and CO coverages are scanned as a function of time. There are clear advantages in following the rates of the catalyzed CO oxidation via calorimetry and gc-ms simultaneously. At lower temperatures the evidence they provide is complementary. CO oxidation and its catalysis of CO oxidation have been extensively studied with hysteresis and oscillations apparent, and the present results suggest the benefits of a combined approach. Silica support porosity may be important in defining activity-temperature hysteresis. FTIR microspectroscopy reveals the chemical heterogeneity of the catalytic surfaces used; it is interesting that the evidence with regard to the dominant CO surface species and their reactivities with regard to surface oxygen for present oxide-supported Pt are different from those seen on graphite-supported Pt.

Assessment of two theoretical methods to estimate potentiometric titration curves of peptides: comparison with experiment.

PubMed

Makowska, Joanna; Bagiñska, Katarzyna; Makowski, Mariusz; Jagielska, Anna; Liwo, Adam; Kasprzykowski, Franciszek; Chmurzyñski, Lech; Scheraga, Harold A

2006-03-09

We compared the ability of two theoretical methods of pH-dependent conformational calculations to reproduce experimental potentiometric titration curves of two models of peptides: Ac-K5-NHMe in 95% methanol (MeOH)/5% water mixture and Ac-XX(A)7OO-NH2 (XAO) (where X is diaminobutyric acid, A is alanine, and O is ornithine) in water, methanol (MeOH), and dimethyl sulfoxide (DMSO), respectively. The titration curve of the former was taken from the literature, and the curve of the latter was determined in this work. The first theoretical method involves a conformational search using the electrostatically driven Monte Carlo (EDMC) method with a low-cost energy function (ECEPP/3 plus the SRFOPT surface-solvation model, assumming that all titratable groups are uncharged) and subsequent reevaluation of the free energy at a given pH with the Poisson-Boltzmann equation, considering variable protonation states. In the second procedure, molecular dynamics (MD) simulations are run with the AMBER force field and the generalized Born model of electrostatic solvation, and the protonation states are sampled during constant-pH MD runs. In all three solvents, the first pKa of XAO is strongly downshifted compared to the value for the reference compounds (ethylamine and propylamine, respectively); the water and methanol curves have one, and the DMSO curve has two jumps characteristic of remarkable differences in the dissociation constants of acidic groups. The predicted titration curves of Ac-K5-NHMe are in good agreement with the experimental ones; better agreement is achieved with the MD-based method. The titration curves of XAO in methanol and DMSO, calculated using the MD-based approach, trace the shape of the experimental curves, reproducing the pH jump, while those calculated with the EDMC-based approach and the titration curve in water calculated using the MD-based approach have smooth shapes characteristic of the titration of weak multifunctional acids with small differences between the dissociation constants. Nevertheless, quantitative agreement between theoretically predicted and experimental titration curves is not achieved in all three solvents even with the MD-based approach, which is manifested by a smaller pH range of the calculated titration curves with respect to the experimental curves. The poorer agreement obtained for water than for the nonaqueous solvents suggests a significant role of specific solvation in water, which cannot be accounted for by the mean-field solvation models.

Surface Characteristics and Adhesion Behavior of Escherichia coli O157:H7: Role of Extracellular Macromolecules

USDA-ARS?s Scientific Manuscript database

Surface macromolecule cleavage experiments were conducted on enterohaemorrhagic Escherichia coli O157:H7 cells to investigate the influence of these macromolecules on cell surface properties. Electrophoretic mobility, hydrophobicity, and titration experiments were carried out on proteinase K treate...

Redox Titration of Ferricyanide to Ferrocyanide with Ascorbic Acid: Illustrating the Nernst Equation and Beer-Lambert Law

ERIC Educational Resources Information Center

Huang, Tina H.; Salter, Gail; Kahn, Sarah L.; Gindt, Yvonne M.

2007-01-01

We have developed a simple, resilient experiment that illustrates the Nernst equation and Beer-Lambert law for our second-semester general chemistry students. In the experiment, the students monitor the reduction of ferricyanide ion, [Fe(CN)[subscript 6

Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2 Diabetes in India.

PubMed

Kovil, Rajiv; Chawla, Manoj; Rajput, Rajesh; Singh, A K; Sinha, Binayak; Ghosal, Samit; Ballani, Piya; Gupta, Sunil; Tanna, Snehal; Bandukwala, S M; Shah, Tejas; Negalur, Vijay; Bhoraskar, Anil; Aravind, S R; Zargar, Abdul H; Kesavadev, Jothydev; Das, Ashok Kumar

2017-02-01

Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM) and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate insulin dosing and titration is also critical to the successful achievement of tight glycaemic control. To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens for both initiation and intensification. Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from approved pack inserts, and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives patient-physician experience in their clinical practice and common therapeutic practices followed in India. Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL). The consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal glucose control.

Surfactant titration of nanoparticle-protein corona.

PubMed

Maiolo, Daniele; Bergese, Paolo; Mahon, Eugene; Dawson, Kenneth A; Monopoli, Marco P

2014-12-16

Nanoparticles (NP), when exposed to biological fluids, are coated by specific proteins that form the so-called protein corona. While some adsorbing proteins exchange with the surroundings on a short time scale, described as a "dynamic" corona, others with higher affinity and long-lived interaction with the NP surface form a "hard" corona (HC), which is believed to mediate NP interaction with cellular machineries. In-depth NP protein corona characterization is therefore a necessary step in understanding the relationship between surface layer structure and biological outcomes. In the present work, we evaluate the protein composition and stability over time and we systematically challenge the formed complexes with surfactants. Each challenge is characterized through different physicochemical measurements (dynamic light scattering, ζ-potential, and differential centrifugal sedimentation) alongside proteomic evaluation in titration type experiments (surfactant titration). 100 nm silicon oxide (Si) and 100 nm carboxylated polystyrene (PS-COOH) NPs cloaked by human plasma HC were titrated with 3-[(3-Cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS, zwitterionic), Triton X-100 (nonionic), sodium dodecyl sulfate (SDS, anionic), and dodecyltrimethylammonium bromide (DTAB, cationic) surfactants. Composition and density of HC together with size and ζ-potential of NP-HC complexes were tracked at each step after surfactant titration. Results on Si NP-HC complexes showed that SDS removes most of the HC, while DTAB induces NP agglomeration. Analogous results were obtained for PS NP-HC complexes. Interestingly, CHAPS and Triton X-100, thanks to similar surface binding preferences, enable selective extraction of apolipoprotein AI (ApoAI) from Si NP hard coronas, leaving unaltered the dispersion physicochemical properties. These findings indicate that surfactant titration can enable the study of NP-HC stability through surfactant variation and also selective separation of certain proteins from the HC. This approach thus has an immediate analytical value as well as potential applications in HC engineering.

Titrating Oxygen Requirements During Exercise: Evaluation of a Standardized Single Walk Test Protocol.

PubMed

Giovacchini, Coral X; Mathews, Anne M; Lawlor, Brian R; MacIntyre, Neil R

2018-04-01

Oxygen supplementation for exercise-induced hypoxemia is a common clinical practice that improves exercise tolerance. However, we know of no standardized exercise oxygen titration protocol using a single walk test. We report our experience with a protocol developed in our laboratory. Our protocol is based on the 6-min walk test (6MWT). Pulse oximetry readings (oxygen saturation [Spo 2 ]) are monitored, and supplemental oxygen is added in 2 L/min increments to keep Spo 2 > 88%. This continues for at least 6 min of walking with the Spo 2 remaining > 88% for at least 3 min. The records of consecutive patients over 4 months undergoing this procedure were reviewed for test performance, oxygen titration results, and adverse events. Two hundred twenty-two patients were tested; only two prematurely terminated the protocol because of intractable dyspnea. One hundred fifty-six patients (38%) required oxygen supplementation, with the first titration most commonly occurring between 1 and 2 min of walking. Nine of the patients had the first titration after 5 min of walking. The average test duration was 7 min (maximum, 15 min). The average number of titrations was 2.2 (maximum six). Sixteen patients could not maintain Spo 2 > 88% for 3 min despite administration of 15 L/min of supplemental oxygen (maximal dose). Our protocol was easily performed as a modification of a standard 6MWT with no serious adverse events. Because it is based on a widely accepted measurement of functional capabilities, and because it determined a stable final oxygen dose for ≥ 3 min of walking in most patients, we believe this protocol can be easily adapted for clinical use. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Titration of biologically active amyloid–β seeds in a transgenic mouse model of Alzheimer's disease

PubMed Central

Morales, Rodrigo; Bravo-Alegria, Javiera; Duran-Aniotz, Claudia; Soto, Claudio

2015-01-01

Experimental evidence in animal models suggests that misfolded Amyloid-β (Aβ) spreads in disease following a prion-like mechanism. Several properties characteristics of infectious prions have been shown for the induction of Aβ aggregates. However, a detailed titration of Aβ misfolding transmissibility and estimation of the minimum concentration of biologically active Aβ seeds able to accelerate pathological changes has not yet been performed. In this study, brain extracts from old tg2576 animals were serially diluted and intra-cerebrally injected into young subjects from the same transgenic line. Animals were sacrificed several months after treatment and brain slices were analyzed for amyloid pathology. We observed that administration of misfolded Aβ was able to significantly accelerate amyloid deposition in young mice, even when the original sample was diluted a million times. The titration curve obtained in this experiment was compared to the natural Aβ load spontaneously accumulated by these mice overtime. Our findings suggest that administration of the largest dose of Aβ seeds led to an acceleration of pathology equivalent to over a year. These results show that active Aβ seeds present in the brain can seed amyloidosis in a titratable manner, similarly as observed for infectious prions. PMID:25879692

Charge-Neutral Constant pH Molecular Dynamics Simulations Using a Parsimonious Proton Buffer.

PubMed

Donnini, Serena; Ullmann, R Thomas; Groenhof, Gerrit; Grubmüller, Helmut

2016-03-08

In constant pH molecular dynamics simulations, the protonation states of titratable sites can respond to changes of the pH and of their electrostatic environment. Consequently, the number of protons bound to the biomolecule, and therefore the overall charge of the system, fluctuates during the simulation. To avoid artifacts associated with a non-neutral simulation system, we introduce an approach to maintain neutrality of the simulation box in constant pH molecular dynamics simulations, while maintaining an accurate description of all protonation fluctuations. Specifically, we introduce a proton buffer that, like a buffer in experiment, can exchange protons with the biomolecule enabling its charge to fluctuate. To keep the total charge of the system constant, the uptake and release of protons by the buffer are coupled to the titration of the biomolecule with a constraint. We find that, because the fluctuation of the total charge (number of protons) of a typical biomolecule is much smaller than the number of titratable sites of the biomolecule, the number of buffer sites required to maintain overall charge neutrality without compromising the charge fluctuations of the biomolecule, is typically much smaller than the number of titratable sites, implying markedly enhanced simulation and sampling efficiency.

Depression May Reduce Adherence during CPAP Titration Trial

PubMed Central

Law, Mandy; Naughton, Matthew; Ho, Sally; Roebuck, Teanau; Dabscheck, Eli

2014-01-01

Study Objectives: Depression is a risk factor for medication non-compliance. We aimed to identify if depression is associated with poorer adherence during home-based autotitrating continuous positive airway pressure (autoPAP) titration. Design: Mixed retrospective-observational study. Setting: Academic center. Participants: Two-hundred forty continuous positive airway pressure-naïve obstructive sleep apnea (OSA) patients. Measurements: Patients underwent approximately 1 week of home-based autoPAP titration with adherence data downloaded from the device. Electronic hospital records were reviewed in a consecutive manner for inclusion. Three areas of potential predictors were examined: (i) demographics and clinical factors, (ii) disease severity, and (iii) device-related variables. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS). Scores on the subscales were categorized as normal or clinical diagnoses of depression (≥ 8) and anxiety (≥ 11). The primary outcome variable was the mean hours of autoPAP used per night. Results: Patients were diagnosed with OSA by either attended polysomnography (n = 73, AHI 25.5[15.1-41.5]) or unattended home oximetry (n = 167, ODI3 34.0[22.4-57.4]) and had home-based autoPAP titration over 6.2 ± 1.2 nights. Mean autoPAP use was 4.5 ± 2.4 hours per night. Multiple linear regression analysis revealed that depression and lower 95th percentile pressures significantly predicted lesser hours of autoPAP use (R2 = 0.19, p < 0.001). Significantly milder OSA in those requiring lower pressures may have confounded the relationship between 95th percentile pressure and autoPAP use. Conclusion: Depression was independently associated with poorer adherence during home-based autoPAP titration. Depression may be a potential target for clinicians and future research aimed at enhancing adherence to autoPAP therapy. Citation: Law M; Naughton M; Ho S; Roebuck T; Dabscheck E. Depression may reduce adherence during CPAP titration trial. J Clin Sleep Med 2014;10(2):163-169. PMID:24532999

Sampling Error in a Particulate Mixture: An Analytical Chemistry Experiment.

ERIC Educational Resources Information Center

Kratochvil, Byron

1980-01-01

Presents an undergraduate experiment demonstrating sampling error. Selected as the sampling system is a mixture of potassium hydrogen phthalate and sucrose; using a self-zeroing, automatically refillable buret to minimize titration time of multiple samples and employing a dilute back-titrant to obtain high end-point precision. (CS)

Oxygen from Hydrogen Peroxide. A Safe Molar Volume-Molar Mass Experiment.

ERIC Educational Resources Information Center

Bedenbaugh, John H.; And Others

1988-01-01

Describes a molar volume-molar mass experiment for use in general chemistry laboratories. Gives background technical information, procedures for the titration of aqueous hydrogen peroxide with standard potassium permanganate and catalytic decomposition of hydrogen peroxide to produce oxygen, and a discussion of the results obtained in three…

Dose titration of sericea lespedeza leaf meal on Haemonchus contortus infection in lambs and kids

USDA-ARS?s Scientific Manuscript database

The objective of three experiments was to determine the impact of supplementing sericea lespedeza (Lespedeza cuneata; SL) in three concentrations in a loose or pelleted diet on gastrointestinal nematodes (GIN) in small ruminants. Experiments on lambs were conducted at the USDA, Agricultural Research...

Pullulan-protamine as efficient haemocompatible gene delivery vector: synthesis and in vitro characterization.

PubMed

Priya, S S; Rekha, M R; Sharma, Chandra P

2014-02-15

Biodegradable non-viral vectors with good transfection efficiency is essential for successful gene delivery. The purpose of this study was to design a non-viral vector by conjugating protamine to pullulan and elucidate the potential use of pullulan protamine conjugate (PPA) as an effective, non toxic and haemocompatible gene delivery system. The particle size and surface charge were measured using Nanosizer. Derivatization was confirmed by NMR, FTIR and DSC analyses. Acid base titration revealed the buffering behaviour of the conjugate. The protection of DNA from nuclease enzyme and interaction of plasma components on the stability of nanoplexes were also analysed. The uptake studies confirmed the plasmid delivery into the nucleus and the inhibitor studies determined the uptake mechanism. Transfection experiments revealed the capability of PPA to cellular uptake in C6 cells and facilitate high gene expression. Thus, PPA proves to be a promising non-viral vector. Copyright © 2013 Elsevier Ltd. All rights reserved.

Wet Labs, Computers, and Spreadsheets.

ERIC Educational Resources Information Center

Durham, Bill

1990-01-01

Described are some commonly encountered chemistry experiments that have been modified for computerized data acquisition. Included are exercises in radioactivity, titration, calorimetry, kinetics, and electrochemistry. Software considerations and laboratory procedures are discussed. (CW)

Iron Analysis by Redox Titration. A General Chemistry Experiment.

ERIC Educational Resources Information Center

Kaufman, Samuel; DeVoe, Howard

1988-01-01

Describes a simplified redox method for total iron analysis suitable for execution in a three-hour laboratory period by general chemistry students. Discusses materials, procedures, analyses, and student performance. (CW)

Edible Acid-Base Indicators.

ERIC Educational Resources Information Center

Mebane, Robert C.; Rybolt, Thomas R.

1985-01-01

Reports on the colors observed during titrations of 15 natural indicators obtained from common fruits and vegetables. These edible indicators can be used for a variety of teacher demonstrations or for simple student experiments. (JN)

A comparative analysis on the binding characteristics of various mammalian albumins towards a multitherapeutic agent, pinostrobin

PubMed Central

FEROZ, Shevin R.; SUMI, Rumana A.; MALEK, Sri N.A.; TAYYAB, Saad

2014-01-01

The interaction of pinostrobin (PS), a multitherapeutic agent with serum albumins of various mammalian species namely, goat, bovine, human, porcine, rabbit, sheep and dog was investigated using fluorescence quench titration and competitive drug displacement experiments. Analysis of the intrinsic fluorescence quenching data revealed values of the association constant, Ka in the range of 1.49 – 6.12 × 104 M−1, with 1:1 binding stoichiometry. Based on the PS–albumin binding characteristics, these albumins were grouped into two classes. Ligand displacement studies using warfarin as the site I marker ligand correlated well with the binding data. Albumins from goat and bovine were found to be closely similar to human albumin on the basis of PS binding characteristics. PMID:25519455

Water-soluble Manganese and Iron Mesotetrakis(carboxyl)porphyrin: DNA Binding, Oxidative Cleavage, and Cytotoxic Activities.

PubMed

Shi, Lei; Jiang, Yi-Yu; Jiang, Tao; Yin, Wei; Yang, Jian-Ping; Cao, Man-Li; Fang, Yu-Qi; Liu, Hai-Yang

2017-06-29

Two new water-soluble metal carboxyl porphyrins, manganese (III) meso -tetrakis (carboxyl) porphyrin and iron (III) meso -tetrakis (carboxyl) porphyrin, were synthesized and characterized. Their interactions with ct-DNA were investigated by UV-Vis titration, fluorescence spectra, viscosity measurement and CD spectra. The results showed they can strongly bind to ct-DNA via outside binding mode. Electrophoresis experiments revealed that both complexes can cleave pBR322 DNA efficiently in the presence of hydrogen peroxide, albeit 2-Mn exhibited a little higher efficiency. The inhibitor tests suggest the oxidative DNA cleavage by these two complexes may involve hydroxyl radical active intermediates. Notably, 2-Mn exhibited considerable photocytotoxicity against Hep G2 cell via triggering a significant generation of ROS and causing disruption of MMP after irradiation.

Chelerythrine down regulates expression of VEGFA, BCL2 and KRAS by arresting G-Quadruplex structures at their promoter regions

PubMed Central

Jana, Jagannath; Mondal, Soma; Bhattacharjee, Payel; Sengupta, Pallabi; Roychowdhury, Tanaya; Saha, Pranay; Kundu, Pallob; Chatterjee, Subhrangsu

2017-01-01

A putative anticancer plant alkaloid, Chelerythrine binds to G-quadruplexes at promoters of VEGFA, BCL2 and KRAS genes and down regulates their expression. The association of Chelerythrine to G-quadruplex at the promoters of these oncogenes were monitored using UV absorption spectroscopy, fluorescence anisotropy, circular dichroism spectroscopy, CD melting, isothermal titration calorimetry, molecular dynamics simulation and quantitative RT-PCR technique. The pronounced hypochromism accompanied by red shifts in UV absorption spectroscopy in conjunction with ethidium bromide displacement assay indicates end stacking mode of interaction of Chelerythrine with the corresponding G-quadruplex structures. An increase in fluorescence anisotropy and CD melting temperature of Chelerythrine-quadruplex complex revealed the formation of stable Chelerythrine-quadruplex complex. Isothermal titration calorimetry data confirmed that Chelerythrine-quadruplex complex formation is thermodynamically favourable. Results of quantative RT-PCR experiment in combination with luciferase assay showed that Chelerythrine treatment to MCF7 breast cancer cells effectively down regulated transcript level of all three genes, suggesting that Chelerythrine efficiently binds to in cellulo quadruplex motifs. MD simulation provides the molecular picture showing interaction between Chelerythrine and G-quadruplex. Binding of Chelerythrine with BCL2, VEGFA and KRAS genes involved in evasion, angiogenesis and self sufficiency of cancer cells provides a new insight for the development of future therapeutics against cancer. PMID:28102286

Synthesis and binding properties of arylethyne-linked porphyrin-zinc complexes for organic electronics applications.

PubMed

Reainthippayasakul, W; Paosawatyanyong, B; Bhanthumnavin, W

2013-05-01

Conjugated meso-alkynyl 5,15-dimesitylporphyrin metal complexes have been synthesized by Sonogashira coupling reaction in good yields. Alkynyl groups were chosen as a link at the meso positions in order to extend the pi-conjugated length of porphyrin rings. These synthesized porphyrin derivatives were characterized by 1H NMR spectroscopy and MALDI-TOF mass spectrometry. Moreover, UV-visible spectroscopy and fluorescence spectroscopy were also used to investigate their photophysical properties. It has been demonstrated that central metal ions as well as meso substituents on porphyrin rings affected the electronic absorption and emission spectra of the compounds. Spectroscopic results revealed that alkyne-linked porphyrin metal complexes showed higher pi-conjugation compared with porphyrin building blocks resulting in red shifts in both absorption and emission spectra. Coordination properties of synthesized porphyrins were preliminarily investigated by UV-visible absorption and fluorescence emission spectroscopic titration with pyridine as axial ligand. The formation of porphyrin-pyridine complexes resulted in significant red shifts in absorption spectra and decrease of fluorescence intensity in emission spectra. Moreover, the 1H NMR titration experiments suggested that central metal ions play an important role to coordinate with pyridine and the coordination of porphyrin zinc(II) complex with pyridine occur in a 1:1 ratio. From these spectroscopic results, alkyne-linked porphyrin metal complexes offer potential applications as materials for optical organic nanosensors.

Leverage principle of retardation signal in titration of double protein via chip moving reaction boundary electrophoresis.

PubMed

Zhang, Liu-Xia; Cao, Yi-Ren; Xiao, Hua; Liu, Xiao-Ping; Liu, Shao-Rong; Meng, Qing-Hua; Fan, Liu-Yin; Cao, Cheng-Xi

2016-03-15

In the present work we address a simple, rapid and quantitative analytical method for detection of different proteins present in biological samples. For this, we proposed the model of titration of double protein (TDP) and its relevant leverage theory relied on the retardation signal of chip moving reaction boundary electrophoresis (MRBE). The leverage principle showed that the product of the first protein content and its absolute retardation signal is equal to that of the second protein content and its absolute one. To manifest the model, we achieved theoretical self-evidence for the demonstration of the leverage principle at first. Then relevant experiments were conducted on the TDP-MRBE chip. The results revealed that (i) there was a leverage principle of retardation signal within the TDP of two pure proteins, and (ii) a lever also existed within these two complex protein samples, evidently demonstrating the validity of TDP model and leverage theory in MRBE chip. It was also showed that the proposed technique could provide a rapid and simple quantitative analysis of two protein samples in a mixture. Finally, we successfully applied the developed technique for the quantification of soymilk in adulterated infant formula. The TDP-MRBE opens up a new window for the detection of adulteration ratio of the poor food (milk) in blended high quality one. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of the kinetic and thermodynamic landscape of RNA folding using a novel application of isothermal titration calorimetry

PubMed Central

Vander Meulen, Kirk A.; Butcher, Samuel E.

2012-01-01

A novel isothermal titration calorimetry (ITC) method was applied to investigate RNA helical packing driven by the GAAA tetraloop–receptor interaction in magnesium and potassium solutions. Both the kinetics and thermodynamics were obtained in individual ITC experiments, and analysis of the kinetic data over a range of temperatures provided Arrhenius activation energies (ΔH‡) and Eyring transition state entropies (ΔS‡). The resulting rich dataset reveals strongly contrasting kinetic and thermodynamic profiles for this RNA folding system when stabilized by potassium versus magnesium. In potassium, association is highly exothermic (ΔH25°C = −41.6 ± 1.2 kcal/mol in 150 mM KCl) and the transition state is enthalpically barrierless (ΔH‡ = −0.6 ± 0.5). These parameters are sigificantly positively shifted in magnesium (ΔH25°C = −20.5 ± 2.1 kcal/mol, ΔH‡ = 7.3 ± 2.2 kcal/mol in 0.5 mM MgCl2). Mixed salt solutions approximating physiological conditions exhibit an intermediate thermodynamic character. The cation-dependent thermodynamic landscape may reflect either a salt-dependent unbound receptor conformation, or alternatively and more generally, it may reflect a small per-cation enthalpic penalty associated with folding-coupled magnesium uptake. PMID:22058128

Contemporary NMR Studies of Protein Electrostatics.

PubMed

Hass, Mathias A S; Mulder, Frans A A

2015-01-01

Electrostatics play an important role in many aspects of protein chemistry. However, the accurate determination of side chain proton affinity in proteins by experiment and theory remains challenging. In recent years the field of nuclear magnetic resonance spectroscopy has advanced the way that protonation states are measured, allowing researchers to examine electrostatic interactions at an unprecedented level of detail and accuracy. Experiments are now in place that follow pH-dependent (13)C and (15)N chemical shifts as spatially close as possible to the sites of protonation, allowing all titratable amino acid side chains to be probed sequence specifically. The strong and telling response of carefully selected reporter nuclei allows individual titration events to be monitored. At the same time, improved frameworks allow researchers to model multiple coupled protonation equilibria and to identify the underlying pH-dependent contributions to the chemical shifts.

Assessment of two theoretical methods to estimate potentiometrictitration curves of peptides: comparison with experiment

PubMed Central

Makowska, Joanna; Bagiñska, Katarzyna; Makowski, Mariusz; Jagielska, Anna; Liwo, Adam; Kasprzykowski, Franciszek; Chmurzyñski, Lech; Scheraga, Harold A.

2008-01-01

We compared the ability of two theoretical methods of pH-dependent conformational calculations to reproduce experimental potentiometric-titration curves of two models of peptides: Ac-K5-NHMe in 95% methanol (MeOH)/5% water mixture and Ac-XX(A)7OO-NH2 (XAO) (where X is diaminobutyric acid, A is alanine, and O is ornithine) in water, methanol (MeOH) and dimethylsulfoxide (DMSO), respectively. The titration curve of the former was taken from the literature, and the curve of the latter was determined in this work. The first theoretical method involves a conformational search using the Electrostatically Driven Monte Carlo (EDMC) method with a low-cost energy function (ECEPP/3 plus the SRFOPT surface-solvation model, assumming that all titratable groups are uncharged) and subsequent reevaluation of the free energy at a given pH with the Poisson-Boltzmann equation, considering variable protonation states. In the second procedure, MD simulations are run with the AMBER force field and the Generalized-Born model of electrostatic solvation, and the protonation states are sampled during constant-pH MD runs. In all three solvents, the first pKa of XAO is strongly downshifted compared to the value for the reference compounds (ethyl amine and propyl amine, respectively); the water and methanol curves have one, and the DMSO curve has two jumps characteristic of remarkable differences in the dissociation constants of acidic groups. The predicted titration curves of Ac-K5-NHMe are in good agreement with the experimental ones; better agreement is achieved with the MD-based method. The titration curves of XAO in methanol and DMSO, calculated using the MD-based approach, trace the shape of the experimental curves, reproducing the pH jump, while those calculated with the EDMC-based approach, and the titration curve in water calculated using the MD-based approach, have smooth shapes characteristic of the titration of weak multifunctional acids with small differences between the dissociation constants. Nevertheless, quantitative agreement between theoretically predicted and experimental titration curves is not achieved in all three solvents even with the MD-based approach which is manifested by a smaller pH range of the calculated titration curves with respect to the experimental curves. The poorer agreement obtained for water than for the non-aqueous solvents suggests a significant role of specific solvation in water, which cannot be accounted for by the mean-field solvation models. PMID:16509748

Single-Molecule Titration in a Protein Nanoreactor Reveals the Protonation/Deprotonation Mechanism of a C:C Mismatch in DNA.

PubMed

Ren, Hang; Cheyne, Cameron G; Fleming, Aaron M; Burrows, Cynthia J; White, Henry S

2018-04-18

Measurement of single-molecule reactions can elucidate microscopic mechanisms that are often hidden from ensemble analysis. Herein, we report the acid-base titration of a single DNA duplex confined within the wild-type α-hemolysin (α-HL) nanopore for up to 3 h, while monitoring the ionic current through the nanopore. Modulation between two states in the current-time trace for duplexes containing the C:C mismatch in proximity to the latch constriction of α-HL is attributed to the base flipping of the C:C mismatch. As the pH is lowered, the rate for the C:C mismatch to flip from the intra-helical state to the extra-helical state ( k intra-extra ) decreases, while the rate for base flipping from the extra-helical state to the intra-helical state ( k extra-intra ) remains unchanged. Both k intra-extra and k extra-intra are on the order of 1 × 10 -2 s -1 to 1 × 10 -1 s -1 and remain stable over the time scale of the measurement (several hours). Analysis of the pH-dependent kinetics of base flipping using a hidden Markov kinetic model demonstrates that protonation/deprotonation occurs while the base pair is in the intra-helical state. We also demonstrate that the rate of protonation is limited by transport of H + into the α-HL nanopore. Single-molecule kinetic isotope experiments exhibit a large kinetic isotope effect (KIE) for k intra-extra ( k H / k D ≈ 5) but a limited KIE for k extra-intra ( k H / k D ≈ 1.3), supporting our model. Our experiments correspond to the longest single-molecule measurements performed using a nanopore, and demonstrate its application in interrogating mechanisms of single-molecule reactions in confined geometries.

Characterization of acid-base properties of two gibbsite samples in the context of literature results.

PubMed

Adekola, F; Fédoroff, M; Geckeis, H; Kupcik, T; Lefèvre, G; Lützenkirchen, J; Plaschke, M; Preocanin, T; Rabung, T; Schild, D

2011-02-01

Two different gibbsites, one commercial and one synthesized according to a frequently applied recipe, were studied in an interlaboratory attempt to gain insight into the origin of widely differing reports on gibbsite acid-base surface properties. In addition to a thorough characterization of the two solids, several methods relevant to the interfacial charging were applied to the two samples: potentiometric titrations to obtain the "apparent" proton related surface charge density, zeta-potential measurements characterizing the potential at the plane of shear, and Attenuated Total Reflection Infrared Spectroscopy (ATR-IR) to obtain information on the variation of counter-ion adsorption with pH (using nitrate as a probe). Values of the IEP at 9-10 and 11.2-11.3 were found for the commercial and synthesized sample, respectively. The experimental observations revealed huge differences in the charging behavior between the two samples. Such differences also appeared in the titration kinetics. A detailed literature review revealed similar disparity with no apparent systematic trend. While previously the waiting time between additions had been advocated to explain such differences among synthesized samples, our results do not support such a conclusion. Instead, we find that the amount of titrant added in each aliquot appears to have a significant influence on the titration curves. While we can relate a number of observations to others, a number of open questions and contradictions remain. We suggest various processes, which can explain the observed behavior. Copyright © 2010 Elsevier Inc. All rights reserved.

Microscale Titration in Schools Titration Competition.

ERIC Educational Resources Information Center

Clark, Michael J.

1998-01-01

Reviews the requirements of the National Titration Competition and describes how a team in a local competition used the technique. Compares microscale titration to conventional titration. Outlines the benefits of employing microscale techniques. (DDR)

Computer Series, 75: Bits and Pieces, 30.

ERIC Educational Resources Information Center

Moore, John W., Ed.

1986-01-01

Identifies six computer-oriented approaches to teaching concepts in chemistry. Describes courseware and equipment involved in various experiments dealing with such topics as polymer configurations, stepper motors, conductometric titration, kinetic spectrophotometry, and overlap integrals. (TW)

Using Mole Ratios of Electrolytic Products of Water for Analysis of Household Vinegar: An Experiment for the Undergraduate Physical Chemistry Laboratory

ERIC Educational Resources Information Center

Dabke, Rajeev B.; Gebeyehu, Zewdu

2012-01-01

A simple 3-h physical chemistry undergraduate experiment for the quantitative analysis of acetic acid in household vinegar is presented. The laboratory experiment combines titration concept with electrolysis and an application of the gas laws. A vinegar sample was placed in the cathode compartment of the electrolysis cell. Electrolysis of water…

Endpoint titration and immunotherapy.

PubMed

King, H C

1985-11-01

Inhalant allergy, or "atopy" as it is now termed, is the best understood form of allergy today. In some circles, it is the only recognized form of allergy. While an overall picture of its effects on the body and a reasonable approach to its treatment now exist, many problems remain to be solved and much improvement in its treatment will probably occur within the next several years. Many new approaches to treatment of aeroallergens are now available; however, all are compared with the skin test, which is and has been the baseline for testing and treatment. Endpoint titration provides a quantitative means for undertaking treatment of aeroallergen sensitivity. In no other way does it differ from the forms of skin testing that have been widely used for generations. The practitioners of endpoint titration feel that this difference is highly significant in simplifying, validating, and shortening the necessary period of therapy. While the concept of endpoint titration is not difficult, it is by definition a quantitative form of testing and requires a degree of expertise in performing it correctly. While a good understanding of the method may be gained from the literature, adequate hands-on experience should be obtained by any physician prior to instituting the technique as a treatment modality. Once mastered, it becomes a reliable baseline for all forms of inhalant allergy care.

Stabilization of the initial electrochemical potential for a metal-based potentiometric titration study of a biosorption process.

PubMed

Naja, Ghinwa; Mustin, Christian; Volesky, Bohumil; Berthelin, Jacques

2006-01-01

An interactive metal-based potentiometric titration method has been developed using an ion selective electrode for studying the sorption of metal cations. The accuracy of this technique was verified by analyzing the metal sorption mechanism for the biomass of Rhizopus arrhizus fungus and diatomite, two dissimilar materials (organic and mineral, strong sorbent and weak sorbent) of a different order of cation exchange capacity. The problem of the initial electrochemical potential was addressed identifying the usefulness of a Na-sulfonic resin as a strong chelating agent applied before the beginning of sorption titration experiments so that the titration curves and the sorption uptake could be quantitatively compared. The resin stabilized the initial electrochemical potential to -405+/-5 mV corresponding to 2 micro gl(-1) of lead concentration in solution. The amounts of lead sorbed by R. arrhizus biomass and diatomite were 0.9 mmol g(-1) (C(e)=5.16 x 10(-2)mM) and 0.052 mmol g(-1) (C(e)=5.97 x 10(-2) mM), respectively. Lead sorption by the fungal biomass was pinpointed to at least two types of chemical active sites. The first type was distinguished by high reactivity and a low number of sites whereas the other was characterized by their higher number and lower reactivity.

Optimal level of continuous positive airway pressure: auto-adjusting titration versus titration with a predictive equation.

PubMed

Choi, Ji Ho; Jun, Young Joon; Oh, Jeong In; Jung, Jong Yoon; Hwang, Gyu Ho; Kwon, Soon Young; Lee, Heung Man; Kim, Tae Hoon; Lee, Sang Hag; Lee, Seung Hoon

2013-05-01

The aims of the present study were twofold. We sought to compare two methods of titrating the level of continuous positive airway pressure (CPAP) - auto-adjusting titration and titration using a predictive equation - with full-night manual titration used as the benchmark. We also investigated the reliability of the two methods in patients with obstructive sleep apnea syndrome (OSAS). Twenty consecutive adult patients with OSAS who had successful, full-night manual and auto-adjusting CPAP titration participated in this study. The titration pressure level was calculated with a previously developed predictive equation based on body mass index and apnea-hypopnea index. The mean titration pressure levels obtained with the manual, auto-adjusting, and predictive equation methods were 9.0 +/- 3.6, 9.4 +/- 3.0, and 8.1 +/- 1.6 cm H2O,respectively. There was a significant difference in the concordance within the range of +/- 2 cm H2O (p = 0.019) between both the auto-adjusting titration and the titration using the predictive equation compared to the full-night manual titration. However, there was no significant difference in the concordance within the range of +/- 1 cm H2O (p > 0.999). When compared to full-night manual titration as the standard method, auto-adjusting titration appears to be more reliable than using a predictive equation for determining the optimal CPAP level in patients with OSAS.

Comparative Quantitative Assessments of Salivary Ion Activity Product for Hydroxyapatite and Buffering Capacity in Children with Different Caries Experience.

PubMed

Anand, Siddharth; Masih, Updesh; Yeluri, Ramakrishna

If a relation exists between salivary I PHA , buffer capacity and caries experience, then this relationship could be used as screening chair side test for caries risk assessment. One hundred ninety seven children aged 4 to 6 years were examined. Data was collected by interview and clinical examination. They were divided into low, moderate and high caries experience group of 20 children each. Two ml of each sample was used to measure the pH value with pH meter. Regarding the buffering capacity, freshly prepared hydrochloric acid (HCl) was titrated into saliva and pH was recorded. The collected saliva samples were sent to Laboratory for measurement of calcium and phosphorus. I PHA was calculated and the negative logarithms of I PHA were used to determine the enamel solubility. The correlation between salivary I PHA , buffering capacity and caries experience were evaluated. There was a significant relation between pH, log I PHA and dental caries experience, it could be considered as a predictor of dental caries. pH measurement after HCl titration in saliva could be used as chair side screening test for the assessment of caries risk.

Determination of biguanide groups in polyhexamethylene biguanide hydrochloride by titrimetric methods.

PubMed

Hattori, Toshiaki; Nakata, Yasuko; Kato, Ryo

2003-11-01

The biguanide concentration of polyhexamethylene biguanide hydrochloride (PHMB-HCl) was measured by non-aqueous titration with HClO4, argentometric titration, the Kjeldhal method, and colloidal titration. The summation value of non-aqueous titration and argentometric titration corresponded to two titrable nitrogens in five nitrogens per one unit of PHMB-HCl, and consisted with the result of the Kjeldhal method to the five nitrogens. The colloidal titration of PHMB-HCl at pH 2.05 was equal to that with the two nitrogens. The relative standard deviations of non-aqueous titration, argentometric titration, the Kjeldhal method, and colloidal titration were 0.50% for 8 runs, 0.13% for 7 runs, 3.61% for 6 runs, and 0.69% for 6 runs, respectively.

Developments in Titrimetry.

ERIC Educational Resources Information Center

Parry-Jones, R.

1980-01-01

Described are some new uses and procedures of titration procedures. Topics included are titration in non-aqueous solvents, thermometric titration and catalytic methods for end-point detection, titration finish in organic elemental analysis, and sub-micro analysis and automatic titration procedures. (CS)

Further optimization of culture method for rat keratinocytes: titration of glucose and sodium chloride.

PubMed

Oku, H; Yamashita, M; Iwasaki, H; Chinen, I

1999-02-01

The present study further improved the serum-free method of culturing rat keratinocytes. To obtain the best growth of rat keratinocytes, we modified our previous serum-free medium (MCDB153 based medium), particularly the amounts of glucose and sodium chloride (NaCl). Titration experiments showed the optimal concentration to be 0.8 mM for glucose and 100 mM for NaCl. This modification eliminated the requirement for albumin, which had been essential for colony formation when our previous medium was used. Titration of glucose and NaCl, followed by adjustment of essential amino acids and growth factors, produced a new formulation. More satisfactory and better growth was achieved with the new medium than with the previous medium. Accumulation of monoalkyldiacylglycerol (MADAG) was consistently noted in this study, representing the unusual lipid profile. A tendency toward normalization was, however, noted with the neutral lipid profile of keratinocytes cultivated in the new medium: lower production of MADAG was obtained with the new formulation, rather than the previous one.

Flow cytometry as an improved method for the titration of Chlamydiaceae and other intracellular bacteria.

PubMed

Käser, T; Pasternak, J A; Hamonic, G; Rieder, M; Lai, K; Delgado-Ortega, M; Gerdts, V; Meurens, F

2016-05-01

Chlamydiaceae is a family of intracellular bacteria causing a range of diverse pathological outcomes. The most devastating human diseases are ocular infections with C. trachomatis leading to blindness and genital infections causing pelvic inflammatory disease with long-term sequelae including infertility and chronic pelvic pain. In order to enable the comparison of experiments between laboratories investigating host-chlamydia interactions, the infectious titer has to be determined. Titer determination of chlamydia is most commonly performed via microscopy of host cells infected with a serial dilution of chlamydia. However, other methods including fluorescent ELISpot (Fluorospot) and DNA Chip Scanning Technology have also been proposed to enumerate chlamydia-infected cells. For viruses, flow cytometry has been suggested as a superior alternative to standard titration methods. In this study we compared the use of flow cytometry with microscopy and Fluorospot for the titration of C. suis as a representative of other intracellular bacteria. Titer determination via Fluorospot was unreliable, while titration via microscopy led to a linear read-out range of 16 - 64 dilutions and moderate reproducibility with acceptable standard deviations within and between investigators. In contrast, flow cytometry had a vast linear read-out range of 1,024 dilutions and the lowest standard deviations given a basic training in these methods. In addition, flow cytometry was faster and material costs were lower compared to microscopy. Flow cytometry offers a fast, cheap, precise, and reproducible alternative for the titration of intracellular bacteria like C. suis. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

Thermometric titration in investigation of the formation of polyanions of molybdenum(VI), tungsten(VI), vanadium(V), and chromium (VI)-I: comparison of thermometric and potentiometric titration curves.

PubMed

Kiba, N; Takeuchi, T

1973-09-01

A new twin-cell thermometric titrator has been devised and used for thermometric titration of solutions of sodium molybdate, sodium tungstate, sodium orthovanadate, ammonium metavanadate, and potassium chromate with perchloric acid. The thermometric titration curves were compared with corresponding pH-titration curves for elucidation of the reactions occurring in the titrations. Thermometric titrimetric methods have been developed for the determination of tungsten, vanadium and chromium.

Enhanced cell uptake via non-covalent decollation of a single-walled carbon nanotube-DNA hybrid with polyethylene glycol-grafted poly(l-lysine) labeled with an Alexa-dye and its efficient uptake in a cancer cell

NASA Astrophysics Data System (ADS)

Fujigaya, Tsuyohiko; Yamamoto, Yuki; Kano, Arihiro; Maruyama, Atsushi; Nakashima, Naotoshi

2011-10-01

The use of single-walled carbon nanotubes (SWNTs) for biomedical applications is a promising approach due to their unique outer optical stimuli response properties, such as a photothermal response triggered by near-IR laser irradiation. The challenging task in order to realize such applications is to render the SWNTs biocompatible. For this purpose, the stable and homogeneous functionalization of the SWNTs with a molecule carrying a biocompatible group is very important. Here, we describe the design and synthesis of a polyanionic SWNT/DNA hybrid combined with a cationic poly(l-lysine) grafted by polyethylene glycol (PLL-g-PEG) to provide a supramolecular SWNT assembly. A titration experiment revealed that the assembly undergoes an approximately 1 : 1 reaction of the SWNT/DNA with PLL-g-PEG. We also found that SWNT/DNA is coated with PLL-g-PEG very homogeneously that avoids the non-specific binding of proteins on the SWNT surface. The experiment using the obtained supramolecular hybrid was carried out in vitro and a dramatic enhancement in the cell uptake efficiency compared to that of the SWNT/DNA hybrid without PLL-g-PEG was found.The use of single-walled carbon nanotubes (SWNTs) for biomedical applications is a promising approach due to their unique outer optical stimuli response properties, such as a photothermal response triggered by near-IR laser irradiation. The challenging task in order to realize such applications is to render the SWNTs biocompatible. For this purpose, the stable and homogeneous functionalization of the SWNTs with a molecule carrying a biocompatible group is very important. Here, we describe the design and synthesis of a polyanionic SWNT/DNA hybrid combined with a cationic poly(l-lysine) grafted by polyethylene glycol (PLL-g-PEG) to provide a supramolecular SWNT assembly. A titration experiment revealed that the assembly undergoes an approximately 1 : 1 reaction of the SWNT/DNA with PLL-g-PEG. We also found that SWNT/DNA is coated with PLL-g-PEG very homogeneously that avoids the non-specific binding of proteins on the SWNT surface. The experiment using the obtained supramolecular hybrid was carried out in vitro and a dramatic enhancement in the cell uptake efficiency compared to that of the SWNT/DNA hybrid without PLL-g-PEG was found. Electronic supplementary information (ESI) available: Additional absorption spectra, DLS plots and PL spectra. See DOI: 10.1039/c1nr10635j

The Greenhouse Effect in a Vial.

ERIC Educational Resources Information Center

Golden, Richard; Sneider, Cary

1989-01-01

Presents an example of a greenhouse-effect experiment from the Climate Protection Institute. Analyzes the amount of carbon dioxide in ambient air, human exhalation, automobile exhaust, and nearly pure carbon dioxide by titrating with ammonia and bromthymol blue. (MVL)

In situ investigation of complex BaSO4 fiber generation in the presence of sodium polyacrylate. 1. Kinetics and solution analysis.

PubMed

Wang, Tongxin; Cölfen, Helmut

2006-10-10

Simple solution analysis of the formation mechanism of complex BaSO(4) fiber bundles in the presence of polyacrylate sodium salt, via a bioinspired approach, is reported. Titration of the polyacrylate solution with Ba(2+) revealed complex formation and the optimum ratio of Ba(2+) to polyacrylate for a slow polymer-controlled mineralization process. This is a much simpler and faster method to determine the appropriate additive/mineral concentration pairs as opposed to more common crystallization experiments in which the additive/mineral concentration is varied. Time-dependent pH measurements were carried out to determine the concentration of solution species from which BaSO(4) supersaturation throughout the fiber formation process can be calculated and the second-order kinetics of the Ba(2+) concentration in solution can be identified. Conductivity measurements, pH measurements, and analytical ultracentrifugation revealed the first formed species to be Ba-polyacrylate complexes. A combination of the solution analysis results and optical microscopic images allows a detailed picture of the complex precipitation and self-organization process, a particle-mediated process involving mesoscopic transformations, to be revealed.

Thermometric titration of sulphate.

PubMed

Williams, M B; Janata, J

1970-06-01

Direct thermometric titration of sulphate with a solution of barium perchlorate is proposed. The stoichiometry of the titration is shown to be critically dependent on the concentration of ethanol in the titration medium. The titration is rapid and suffers from only a few interferences.

[Photometric micro-titration model of DPPH radicals scavenging activity and its application].

PubMed

Gao, Yun-tao; Wei, Wei; Ye, Li-qing; Li, Xiao-fen; Liu, Ping; Zhang, Hong-jiao; Yang, Lu; Yu, Jiao-jiao; Cha, Jia-wei

2015-02-01

In the present paper, the stoichiometric ratio (R) for the interreaction of DPPH radicals with the antoxidant was employed as a evaluation index for DPPH radicals scavenging activity of antioxidants. This evaluation index was related only with the stoichiometric relationship between DPPH radicals and the antioxidant, not the relationship with the initial DPPH amount and the volume of sample, which could offer a solution for the problem of poor comparability of EC50 under different conditions. A novel photometric micro-titration method was proposed for the determination of the stoichiometric ratio (R) for the interreaction of DPPH radicals with the antoxidant. The titration equation was established based on the absorbance difference (deltaA) of DPPH radicals in the titration process and the added amount of antoxidant. The stoichiometric ratio (R) for the reaction of DPPH radicals with the addition amount of antoxidant was determined by the titration equation obtained, while, the DPPH median elimination concentration (EC50) of antoxidant can be calculated by the stoichiometric ratio (R). The above photometric micro-titration model was verified using rutin as DPPH radicals scavenger. As experiment results, the stoichiometric ratio (R) of DPPH radicals to rutin was determined to be in the range of 1.817-1.846. The calculated value of EC50 was 1.196 x 10(-3), 2.392 x 10(-3), 4.819 x 10(-3) and 7.292 x 10(-3) mg x mL(-1) for 1.12 x 10(-7), 2.24 x 10(-7), 4.48 x 10(-7) and 6.72 x 10(-7) mol of the additon amount of DPPH radicals, respectively. The proposed method has better precision and reliability with smaller amount of sample than conventional method. While, the obtained stoichiometric ratio value (R) of rutin was employed to calculate the rutin median elimination concentration for DPPH EC50) according to the conditions as reported in the literatures, and the calculated results were consistent with that reported in the literatures.

Direct Sensing of Total Acidity by Chronopotentiometric Flash Titrations at Polymer Membrane Ion-Selective Electrodes

PubMed Central

Gemene, Kebede L.; Bakker, Eric

2008-01-01

Polymer membrane ion-selective electrodes containing lipophilic ionophores are traditionally interrogated by zero current potentiometry, which, ideally, gives information on the sample activity of ionic species. It is shown here that a discrete cathodic current pulse across an H+-selective polymeric membrane doped with the ionophore ETH 5294 may be used for the chronopotentiometric detection of pH in well buffered samples. However, a reduction in the buffer capacity leads to large deviations from the expected Nernstian response slope. This is explained by the local depletion of hydrogen ions at the sample-membrane interface as a result of the galvanostatically imposed ion flux in direction of the membrane. This depletion is found to be a function of the total acidity of the sample and can be directly monitored chronopotentiometrically in a flash titration experiment. The subsequent application of a baseline potential pulse reverses the extraction process of the current pulse, allowing one to interrogate the sample with minimal perturbation. In one protocol, total acidity is found to be proportional to the magnitude of applied current at the flash titration endpoint. More conveniently, the square root of the flash titration endpoint time observed at a fixed applied current is a linear function of the total acid concentration. This suggests that it is possible to perform rapid localized pH titrations at ion-selective electrodes without the need for volumetric titrimetry. The technique is explored here for acetic acid, MES and citric acid with promising results. Polymeric membrane electrodes on the basis of poly(vinyl chloride) plasticized with o-nitrophenyloctylether in a 1:2 mass ratio may be used for the detection of acids of up to ca. 1 mM concentration, with flash titration times on the order of a few seconds. Possible limitations of the technique are discussed, including variations of the acid diffusion coefficients and influence of electrical migration. PMID:18370399

Hydrophobic Peptides Affect Binding of Calmodulin and Ca2+ as Explored by H/D Amide Exchange and Mass Spectrometry

PubMed Central

Sperry, Justin B.; Huang, Richard Y-C.; Zhu, Mei M.; Rempel, Don L.; Gross, Michael L.

2010-01-01

Calmodulin (CaM), a ubiquitous intracellular sensor protein, binds Ca2+ and interacts with various targets as part of signal transduction. Using hydrogen/deuterium exchange (H/DX) and a high resolution PLIMSTEX (Protein-Ligand Interactions by Mass Spectrometry, Titration, and H/D Exchange) protocol, we examined five different states of calmodulin: calcium-free, calcium-loaded, and three states of calcium-loaded in the presence of either melittin, mastoparan, or skeletal myosin light-chain kinase (MLCK). When CaM binds Ca2+, the extent of HDX decreased, consistent with the protein becoming stabilized upon binding. Furthermore, Ca2+-saturated calmodulin exhibits increased protection when bound to the peptides, forming high affinity complexes. The protocol reveals significant changes in EF hands 1, 3, and 4 with saturating levels of Ca2+. Titration of the protein using PLIMSTEX provides the binding affinity of Ca2+ to calmodulin within previously reported values. The affinities of calmodulin to Ca2+ increase by factors of 300 and 1000 in the presence of melittin and mastoparan, respectively. A modified PLIMSTEX protocol whereby the protein is digested to component peptides gives a region-specific titration. The titration data taken in this way show a decrease in the root mean square fit of the residuals, indicating a better fit of the data. The global H/D exchange results and those obtained in a region-specific way provide new insight into the Ca2+-binding properties of this well-studied protein. PMID:21765646

A novel approach for high precision rapid potentiometric titrations: application to hydrazine assay.

PubMed

Sahoo, P; Malathi, N; Ananthanarayanan, R; Praveen, K; Murali, N

2011-11-01

We propose a high precision rapid personal computer (PC) based potentiometric titration technique using a specially designed mini-cell to carry out redox titrations for assay of chemicals in quality control laboratories attached to industrial, R&D, and nuclear establishments. Using this technique a few microlitre of sample (50-100 μl) in a total volume of ~2 ml solution can be titrated and the waste generated after titration is extremely low comparing to that obtained from the conventional titration technique. The entire titration including online data acquisition followed by immediate offline analysis of data to get information about concentration of unknown sample is completed within a couple of minutes (about 2 min). This facility has been created using a new class of sensors, viz., pulsating sensors developed in-house. The basic concept in designing such instrument and the salient features of the titration device are presented in this paper. The performance of the titration facility was examined by conducting some of the high resolution redox titrations using dilute solutions--hydrazine against KIO(3) in HCl medium, Fe(II) against Ce(IV) and uranium using Davies-Gray method. The precision of titrations using this innovative approach lies between 0.048% and 1.0% relative standard deviation in different redox titrations. With the evolution of this rapid PC based titrator it was possible to develop a simple but high precision potentiometric titration technique for quick determination of hydrazine in nuclear fuel dissolver solution in the context of reprocessing of spent nuclear fuel in fast breeder reactors. © 2011 American Institute of Physics

A novel approach for high precision rapid potentiometric titrations: Application to hydrazine assay

NASA Astrophysics Data System (ADS)

Sahoo, P.; Malathi, N.; Ananthanarayanan, R.; Praveen, K.; Murali, N.

2011-11-01

We propose a high precision rapid personal computer (PC) based potentiometric titration technique using a specially designed mini-cell to carry out redox titrations for assay of chemicals in quality control laboratories attached to industrial, R&D, and nuclear establishments. Using this technique a few microlitre of sample (50-100 μl) in a total volume of ˜2 ml solution can be titrated and the waste generated after titration is extremely low comparing to that obtained from the conventional titration technique. The entire titration including online data acquisition followed by immediate offline analysis of data to get information about concentration of unknown sample is completed within a couple of minutes (about 2 min). This facility has been created using a new class of sensors, viz., pulsating sensors developed in-house. The basic concept in designing such instrument and the salient features of the titration device are presented in this paper. The performance of the titration facility was examined by conducting some of the high resolution redox titrations using dilute solutions--hydrazine against KIO3 in HCl medium, Fe(II) against Ce(IV) and uranium using Davies-Gray method. The precision of titrations using this innovative approach lies between 0.048% and 1.0% relative standard deviation in different redox titrations. With the evolution of this rapid PC based titrator it was possible to develop a simple but high precision potentiometric titration technique for quick determination of hydrazine in nuclear fuel dissolver solution in the context of reprocessing of spent nuclear fuel in fast breeder reactors.

Characterization of KCNE1 inside Lipodisq Nanoparticles for EPR Spectroscopic Studies of Membrane Proteins.

PubMed

Sahu, Indra D; Zhang, Rongfu; Dunagan, Megan M; Craig, Andrew F; Lorigan, Gary A

2017-06-01

EPR spectroscopic studies of membrane proteins in a physiologically relevant native membrane-bound state are extremely challenging due to the complexity observed in inhomogeneity sample preparation and dynamic motion of the spin-label. Traditionally, detergent micelles are the most widely used membrane mimetics for membrane proteins due to their smaller size and homogeneity, providing high-resolution structure analysis by solution NMR spectroscopy. However, it is often difficult to examine whether the protein structure in a micelle environment is the same as that of the respective membrane-bound state. Recently, lipodisq nanoparticles have been introduced as a potentially good membrane mimetic system for structural studies of membrane proteins. However, a detailed characterization of a spin-labeled membrane protein incorporated into lipodisq nanoparticles is still lacking. In this work, lipodisq nanoparticles were used as a membrane mimic system for probing the structural and dynamic properties of the integral membrane protein KCNE1 using site-directed spin labeling EPR spectroscopy. The characterization of spin-labeled KCNE1 incorporated into lipodisq nanoparticles was carried out using CW-EPR titration experiments for the EPR spectral line shape analysis and pulsed EPR titration experiment for the phase memory time (T m ) measurements. The CW-EPR titration experiment indicated an increase in spectral line broadening with the addition of the SMA polymer which approaches close to the rigid limit at a lipid to polymer weight ratio of 1:1, providing a clear solubilization of the protein-lipid complex. Similarly, the T m titration experiment indicated an increase in T m values with the addition of SMA polymer and approaches ∼2 μs at a lipid to polymer weight ratio of 1:2. Additionally, CW-EPR spectral line shape analysis was performed on six inside and six outside the membrane spin-label probes of KCNE1 in lipodisq nanoparticles. The results indicated significant differences in EPR spectral line broadening and a corresponding inverse central line width between spin-labeled KCNE1 residues located inside and outside of the membrane for lipodisq nanoparticle samples when compared to lipid vesicle samples. These results are consistent with the solution NMR structure of KCNE1. This study will be beneficial for researchers working on studying the structural and dynamic properties of membrane proteins.

Multi-complexity measures of heart rate variability and the effect of vasopressor titration: a prospective cohort study of patients with septic shock.

PubMed

Brown, Samuel M; Sorensen, Jeffrey; Lanspa, Michael J; Rondina, Matthew T; Grissom, Colin K; Shahul, Sajid; Mathews, V J

2016-10-10

Septic shock is a common and often devastating syndrome marked by severe cardiovascular dysfunction commonly managed with vasopressors. Whether markers of heart rate complexity before vasopressor up-titration could be used to predict success of the up-titration is not known. We studied patients with septic shock requiring vasopressor, newly admitted to the intensive care unit. We measured the complexity of heart rate variability (using the ratio of fractal exponents from detrended fluctuation analysis) in the 5 min before all vasopressor up-titrations in the first 24 h of an intensive care unit (ICU) admission. A successful up-titration was defined as one that did not require further up-titration (or decrease in mean arterial pressure) for 60 min. We studied 95 patients with septic shock, with a median APACHE II of 27 (IQR: 20-37). The median number of up-titrations, normalized to 24 h, was 12.2 (IQR: 8-17) with a maximum of 49. Of the up-titrations, the median proportion of successful interventions was 0.28 (IQR: 0.12-0.42). The median of mean arterial pressure (MAP) at the time of a vasopressor up-titration was 66 mmHg; the average infusion rate of norepinephrine at the time of an up-titration was 0.11 mcg/kg/min. The ratio of fractal exponents was not associated with successful up-titration on univariate or multivariate regression. On exploratory secondary analyses, however, the long-term fractal exponent was associated (p = 0.003) with success of up-titration. Independent of heart rate variability, MAP was associated (p < 0.001) with success of vasopressor up-titration, while neither Sequential Organ Failure Assessment (SOFA) nor Acute Physiology and Chronic Health Evaluation II (APACHE II) score was associated with vasopressor titration. Only a third of vasopressor up-titrations were successful among patients with septic shock. MAP and the long-term fractal exponent were associated with success of up-titration. These two, complementary variables may be important to the development of rational vasopressor titration protocols.

Exopolysaccharides regulate calcium flow in cariogenic biofilms

PubMed Central

Varenganayil, Muth M.; Decho, Alan W.

2017-01-01

Caries-associated biofilms induce loss of calcium from tooth surfaces in the presence of dietary carbohydrates. Exopolysaccharides (EPS) provide a matrix scaffold and an abundance of primary binding sites within biofilms. The role of EPS in binding calcium in cariogenic biofilms is only partially understood. Thus, the aim of the present study is to investigate the relationship between the calcium dissolution rates and calcium tolerance of caries-associated bacteria and yeast as well as to examine the properties of EPS to quantify its binding affinity for dissolved calcium. Calcium dissolution was measured by dissolution zones on Pikovskaya’s agar. Calcium tolerance was assessed by isothermal microcalorimetry (IMC) by adding CaCl2 to the bacterial cultures. Acid-base titration and Fourier transform infrared (FTIR) spectroscopy were used to identify possible functional groups responsible for calcium binding, which was assessed by isothermal titration calorimetry (ITC). Lactobacillus spp. and mutans streptococci demonstrated calcium dissolution in the presence of different carbohydrates. All strains that demonstrated high dissolution rates also revealed higher rates of calcium tolerance by IMC. In addition, acidic functional groups were predominantly identified as possible binding sites for calcium ions by acid-base titration and FTIR. Finally, ITC revealed EPS to have a higher binding affinity for calcium compared, for example, to lactic acid. In conclusion, this study illustrates the role of EPS in terms of the calcium tolerance of cariogenic microbiota by determining the ability of EPS to control free calcium concentrations within the biofilms as a self-regulating mode of action in the pathogenesis of dental caries. PMID:29023506

Determining a Solubility Product Constant by Potentiometric Titration to Increase Students' Conceptual Understanding of Potentiometry and Titrations

ERIC Educational Resources Information Center

Grabowski, Lauren E.; Goode, Scott R.

2017-01-01

Potentiometric titrations are widely taught in first-year undergraduate courses to connect electrochemistry, stoichiometry, and equilibria and to reinforce acid-base titrations. Students perform a potentiometric titration that is then analyzed to determine analyte concentrations and the solubility product constant of the solid species.

Theoretical problems associated with the use of acetic anhydride as a co-solvent for the non-aqueous titration of hydrohalides of organic bases and quaternary ammonium salts.

PubMed

Völgyi, Gergely; Béni, Szabolcs; Takács-Novák, Krisztina; Görög, Sándor

2010-01-05

A potentiometric titration study of organic base hydrohalides and quaternary ammonium salts using perchloric acid as the titrant and a mixture of acetic anhydride and acetic acid as the solvent was carried out and the titration mixture was analysed by NMR in order to clarify the chemistry of the reactions involved. It was found that in contrast to the general belief the formation of acetyl halides and titratable free acetate ion does not take place prior to the titration but NMR spectra proved the formation of acetyl halides in the course of the titration. This observation and the fact that the shape of the titration curves depends on the nature of the hydrohaloic acid bound to the base or of the anion in the quaternary ammonium salts led to the conclusion that the titrating agent is acetyl perchlorate formed in situ during the titration. Equations of the reactions involved in the titration process are shown in the paper.

A new insight into the interaction of ZnO with calf thymus DNA through surface defects.

PubMed

Das, Sumita; Chatterjee, Sabyasachi; Pramanik, Srikrishna; Devi, Parukuttyamma Sujatha; Kumar, Gopinatha Suresh

2018-01-01

Experimental evidences on the binding interaction of ZnO and Calf Thymus (CT) DNA using several biophysical techniques are the centre of interest of the present study. The interaction of ZnO with CT DNA has been investigated in detail by absorption spectral study, fluorescence titration, Raman analysis, zeta potential measurement, viscometric experiment along with thermal melting study and microscopic analysis. Steady-state fluorescence study revealed the quenching (48%) of the surface defect related peak intensity of ZnO on interaction with DNA. The optimized concentration of ZnO and DNA to obtain this level of quenching has been found to be 0.049mM and 1.027μM, respectively. Additional fluorescence study with 8-hydroxy-5-quinoline (HQ) as a fluorescence probe for Zn 2+ ruled out the dissolution effect of ZnO under the experimental conditions. DNA conjugation on the surface of ZnO was also supported by Raman study. The quantitative variation in conductivity as well as electrophoretic mobility indicated significant interaction of ZnO with the DNA molecule. Circular dichroism (CD) and viscometry titrations provided clear evidence in support of the conformational retention of the DNA on interaction with ZnO. The binding interaction was found to be predominantly entropy driven in nature. The bio-physical studies presented in this paper exploring ZnO-CT DNA interaction could add a new horizon to understand the interaction between metal oxide and DNA. Copyright © 2017. Published by Elsevier B.V.

Efficient analysis of stochastic gene dynamics in the non-adiabatic regime using piecewise deterministic Markov processes

PubMed Central

2018-01-01

Single-cell experiments show that gene expression is stochastic and bursty, a feature that can emerge from slow switching between promoter states with different activities. In addition to slow chromatin and/or DNA looping dynamics, one source of long-lived promoter states is the slow binding and unbinding kinetics of transcription factors to promoters, i.e. the non-adiabatic binding regime. Here, we introduce a simple analytical framework, known as a piecewise deterministic Markov process (PDMP), that accurately describes the stochastic dynamics of gene expression in the non-adiabatic regime. We illustrate the utility of the PDMP on a non-trivial dynamical system by analysing the properties of a titration-based oscillator in the non-adiabatic limit. We first show how to transform the underlying chemical master equation into a PDMP where the slow transitions between promoter states are stochastic, but whose rates depend upon the faster deterministic dynamics of the transcription factors regulated by these promoters. We show that the PDMP accurately describes the observed periods of stochastic cycles in activator and repressor-based titration oscillators. We then generalize our PDMP analysis to more complicated versions of titration-based oscillators to explain how multiple binding sites lengthen the period and improve coherence. Last, we show how noise-induced oscillation previously observed in a titration-based oscillator arises from non-adiabatic and discrete binding events at the promoter site. PMID:29386401

Energetics of genome ejection from phage revealed by isothermal titration calorimetry

NASA Astrophysics Data System (ADS)

Jeembaeva, Meerim; Jonsson, Bengt; Castelnovo, Martin; Evilevitch, Alex

2009-03-01

It has been experimentally shown that ejection of double-stranded DNA from phage is driven by internal pressure reaching tens of atmospheres. This internal pressure is partially responsible for delivery of DNA into the host cell. While several theoretical models and simulations nicely describe the experimental data of internal forces either resisting active packaging or equivalently favoring spontaneous ejection, there are no direct energy measurements available that would help to verify how quantitative these theories are. We performed direct measurements of the enthalpy responsible for DNA ejection from phage λ, using Isothermal Titration Calorimetry. The phage capsids were ``opened'' in vitro by titrating λ into a solution with LamB receptor and the enthalpy of DNA ejection process was measured. In his way, enthalpy stored in λ was determined as a function of packaged DNA length comparing wild-type phage λ (48.5 kb) with a shorter λ-DNA length mutant (37.7 kb). The temperature dependence of the ejection enthalpy was also investigated. The values obtained were in good agreement with existing models and provide a better understanding of ds- DNA packaging and release mechanisms in motor-packaged viruses (e.g., tailed bacteriophages, Herpes Simplex, and adenoviruses).

Sailing on the "C": A Vitamin Titration with a Twist

NASA Astrophysics Data System (ADS)

Sowa, S.; Kondo, A. E.

2003-05-01

The experiment takes the traditional redox titration of vitamin C using iodine with starch as an indicator, and presents it to the student as a challenge in guided-inquiry format. Two versions, with different levels of difficulty, are provided, to accommodate students with varying levels of problem-solving skills. The "challenge" is both quantitative and qualitative: if you were an eighteenth-century sea captain packing for a voyage to the New World, would you take oranges, lemons, limes, or grapefruits to prevent your crew from getting scurvy? The challenge ties in history, nutrition, and health with chemistry, and provides students an opportunity to work with familiar food products in the laboratory.

Droplet-counting Microtitration System for Precise On-site Analysis.

PubMed

Kawakubo, Susumu; Omori, Taichi; Suzuki, Yasutada; Ueta, Ikuo

2018-01-01

A new microtitration system based on the counting of titrant droplets has been developed for precise on-site analysis. The dropping rate was controlled by inserting a capillary tube as a flow resistance in a laboratory-made micropipette. The error of titration was 3% in a simulated titration with 20 droplets. The pre-addition of a titrant was proposed for precise titration within an error of 0.5%. The analytical performances were evaluated for chelate titration, redox titration and acid-base titration.

[Comparison of different continuous positive airway pressure titration methods for obstructive sleep apnea hypopnea syndrome].

PubMed

Li, Jingjing; Ye, Jingying; Zhang, Peng; Kang, Dan; Cao, Xin; Zhang, Yuhuan; Ding, Xiu; Zheng, Li; Li, Hongguang; Bian, Qiuli

2014-10-01

To explore whether there were differences between the results of automatic titration and the results of manual titration for positive airway pressure treatment in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and its influencing factors, the results might provide a theoretical basis for the rational use of two pressure titration methods. Sixty one patients with OSAHS were included in this study. All patients underwent a manual titration and an automatic titration within one week. The clinical informations, polysomnography data, and the results of both two titration of all patients were obtained for analysis. The overall apnea/hypopnea index was (63.1 ± 17.7)/h, with a range of 14.9/h to 110.4/h. The treatment pressure of manual titration was (8.4 ± 2.1) cmH(2)O, which was significantly lower than the treatment pressure of automatic titration, (11.5 ± 2.7) cmH(2)O (t = -9.797, P < 0.001). After using a ΔP of 3 cmH(2)O for the cutoff value (ΔP was defined as the difference of automatic titration and manual titration), it was found that the pressure of automatic titration was significantly higher in patients with a ΔP > 3 cmH(2)O than in patients with a ΔP ≤ 3 cmH(2)O, which was (13.3 ± 2.3) cmH(2)O vs (10.0 ± 2.0) cmH(2)O (t = -6.159, P < 0.001). However, there were no differences for the pressure of manual titration between these two groups, which was (8.6 ± 2.4) cmH(2)O vs (8.3 ± 2.0)cmH(2)O (P > 0.05). There was no significant difference in age, body mass index, neck circumference, abdomen circumference, apnea hypopnea index, and arterial oxygen saturation between these two groups. The treatment pressure of automatic titration is usually higher than that of manual titration. For patients with a high treatment pressure which is derived from automatic titration, a suggestion about manual titration could be given to decrease the potential treatment pressure of continuous positive airway pressure, which may be helpful in improving the comfortableness and the compliance of this treatment.

Manufacturing of a Secretoneurin Drug Delivery System with Self-Assembled Protamine Nanoparticles by Titration

PubMed Central

Scheicher, Bernhard; Lorenzer, Cornelia; Gegenbauer, Katrin; Partlic, Julia; Andreae, Fritz; Kirsch, Alexander H.; Rosenkranz, Alexander R.; Werzer, Oliver

2016-01-01

Since therapeutic peptides and oligonucleotides are gathering interests as active pharmaceutical ingredients (APIs), nanoparticulate drug delivery systems are becoming of great importance. Thereby, the possibility to design drug delivery systems according to the therapeutic needs of APIs enhances clinical implementation. Over the last years, the focus of our group was laid on protamine-oligonucleotide-nanoparticles (so called proticles), however, the possibility to modify the size, zeta potential or loading efficiencies was limited. Therefore, at the present study we integrated a stepwise addition of protamine (titration) into the formation process of proticles loaded with the angiogenic neuropeptide secretoneurin (SN). A particle size around 130 nm was determined when proticles were assembled by the commonly used protamine addition at once. Through application of the protamine titration process it was possible to modify and adjust the particle size between approx. 120 and 1200 nm (dependent on mass ratio) without influencing the SN loading capacity. Dynamic light scattering pointed out that the difference in particle size was most probably the result of a secondary aggregation. Initially-formed particles of early stages in the titration process aggregated towards bigger assemblies. Atomic-force-microscopy images also revealed differences in morphology along with different particle size. In contrast, the SN loading was only influenced by the applied mass ratio, where a slight saturation effect was observable. Up to 65% of deployed SN could be imbedded into the proticle matrix. An in-vivo biodistribution study (i.m.) showed a retarded distribution of SN from the site of injection after the application of a SN-proticle formulation. Further, it was demonstrated that SN loaded proticles can be successfully freeze-dried and resuspended afterwards. To conclude, the integration of the protamine titration process offers new possibilities for the formulation of proticles in order to address key parameters of drug delivery systems as size, API loading or modified drug release. PMID:27828968

A new approach to flow-batch titration. A monosegmented flow titrator with coulometric reagent generation and potentiometric or biamperometric detection.

PubMed

de Aquino, Emerson Vidal; Rohwedder, Jarbas José Rodrigues; Pasquini, Celio

2006-11-01

Monosegmented flow analysis (MSFA) has been used as a flow-batch system to produce a simple, robust, and mechanized titrator that enables true titrations to be performed without the use of standards. This paper also introduces the use of coulometry with monosegmented titration by proposing a versatile flow cell. Coulometric generation of the titrand is attractive for titrations performed in monosegmented systems, because the reagent can be added without increasing the volume of sample injected. Also, biamperomeric and potentiometric detection of titration end-points can increase the versatility of the monosegmented titrator. The cell integrates coulometric generation of the titrand with detection of end-point by potentiometry or biamperometry. The resulting titrator is a flow-batch system in which the liquid monosegment, constrained by the interfaces of the gaseous carrier stream, plays the role of a sample of known volume to be titrated. The system has been used for determination of ascorbic acid, by coulometric generation of I2 with biamperometric detection, and for determination of Fe(II), by coulometric generation of Ce(IV) with potentiometric detection of the end-point, both in feed supplements.

Comparison of manual versus automatic continuous positive airway pressure titration and the development of a predictive equation for therapeutic continuous positive airway pressure in Chinese patients with obstructive sleep apnoea.

PubMed

Luo, Jiaying; Xiao, Sichang; Qiu, Zhihui; Song, Ning; Luo, Yuanming

2013-04-01

Whether the therapeutic nasal continuous positive airway pressure (CPAP) derived from manual titration is the same as derived from automatic titration is controversial. The purpose of this study was to compare the therapeutic pressure derived from manual titration with automatic titration. Fifty-one patients with obstructive sleep apnoea (OSA) (mean apnoea/hypopnoea index (AHI) = 50.6 ± 18.6 events/h) who were newly diagnosed after an overnight full polysomnography and who were willing to accept CPAP as a long-term treatment were recruited for the study. Manual titration during full polysomnography monitoring and unattended automatic titration with an automatic CPAP device (REMstar Auto) were performed. A separate cohort study of one hundred patients with OSA (AHI = 54.3 ± 18.9 events/h) was also performed by observing the efficacy of CPAP derived from manual titration. The treatment pressure derived from automatic titration (9.8 ± 2.2 cmH(2)O) was significantly higher than that derived from manual titration (7.3 ± 1.5 cmH(2)O; P < 0.001) in 51 patients. The cohort study of 100 patients showed that AHI was satisfactorily decreased after CPAP treatment using a pressure derived from manual titration (54.3 ± 18.9 events/h before treatment and 3.3 ± 1.7 events/h after treatment; P < 0.001). The results suggest that automatic titration pressure derived from REMstar Auto is usually higher than the pressure derived from manual titration. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Determination of the Effect of Various Modes of Cooking on the Vitamin C Content of a Common Food, Green Pepper: An Introductory Biochemistry Experiment.

ERIC Educational Resources Information Center

Johnson, Eric R.

1988-01-01

Describes a laboratory experiment that measures the amount of ascorbic acid destroyed by food preparation methods (boiling and steaming). Points out that aqueous extracts of cooked green pepper samples can be analyzed for ascorbic acid by a relatively simple redox titration. Lists experimental procedure for four methods of preparation. (MVL)

Computer controlled titration with piston burette or peristaltic pump - a comparison.

PubMed

Hoffmann, W

1996-09-01

The advantages and problems of the use of piston burettes and peristaltic pumps for dosage of titrant solutions in automatic titrations are shown. For comparison, only the dosing devices were exchanged and all other components and conditions remained unchanged. The results of continuous acid base titration show good agreement and comparable reproducibility. Potentiometric sensors (glass electrodes) with different equilibration behaviour influence the results. The capability of such electrodes was tested. Conductometric measurements allow a much faster detection because there is no equilibration of electrodes. Piston burettes should be used for titration with very high precision, titration with organic solvents and slow titrations. Peristaltic pumps seem to be more suitable for continuous titrations and long time operation without service.

Homemade Equipment for the Teaching of Electrochemistry at Advanced Level: Part III.

ERIC Educational Resources Information Center

Chan, K. M.

1985-01-01

Describes: (1) thermometric titrations; (2) EM-5 equipment (consisting of a thermal sensor, calorimeter, and input-buffered amplifier); (3) acid-base titrations; (4) precipitation titrations; and (5) redox titrations. Detailed procedures are included. (JN)

Preparation and characterization of polymer-coated core-shell structured magnetic microbeads

NASA Astrophysics Data System (ADS)

Liu, Z. L.; Ding, Z. H.; Yao, K. L.; Tao, J.; Du, G. H.; Lu, Q. H.; Wang, X.; Gong, F. L.; Chen, X.

2003-09-01

Composite microbeads consisting of polymer-coated iron oxide nanoparticles are prepared by the microemulsion polymerization of styrene, divinyl benzene and methacrylic acid in the presence of emulsifiers. Fourier transform infrared spectrometer analysis indicates the presence of -COOH groups and Fe 3O 4 of the microbeads. The amount of -COOH groups localized on the surface, which is about 0.15 mmol/g, is determined by conductometric titration. Transmission electron microscope picture reveals that the microbeads have a core-shell structure. The dissolving experiments of microbeads in hydrochloric acid and toluene further identify the core-shell structure. Optical microscope indicates that the magnetic microbeads have uniform and spherical forms with the size of 1-5 μm. Magnetic sensitivity measurement indicates that the microbeads can be used conveniently. Magnetic property measurement shows very little residual magnetization and coercivity, which are below 0.5 emu/g and around 15 Oe, respectively. The magnetic properties are greatly related to the particle sizes. The thermal gravity analysis result shows the improvement of thermal stability. The experiment of immobilized antibody indicates that the functional groups on the surface are appropriate.

Conformational properties of two exopolysaccharides produced by Inquilinus limosus, a cystic fibrosis lung pathogen.

PubMed

Kuttel, Michelle; Ravenscroft, Neil; Foschiatti, Michela; Cescutti, Paola; Rizzo, Roberto

2012-03-01

Inquilinus limosus is a multi-resistant bacterium found in the respiratory tract of patients with cystic fibrosis. This bacterium produces two unique fully pyruvylated exopolysaccharides in similar quantities: an α-(1→2)-linked mannan and a β-(1→3)-linked glucan. We employed molecular modelling methods to probe the characteristic conformations and dynamics of these polysaccharides, with corroboration from potentiometric titrations and circular dichroism experiments. Our calculations reveal different structural motifs for the mannan and glucan polysaccharides: the glucan forms primarily right-handed helices with a wide range of extensions, while the mannan forms only left-handed helices. This finding is supported by our circular dichroism experiments. Our calculations also show that the (1→3)-β-d-Glcp linkage is more dynamically flexible than the (1→2)-α-d-Manp: the glucan characteristically forms a range of wide helices with large central cavities. In contrast, the mannan forms rigid regular 'bottlebrush' helices with a minimal central cavity. The widely different character of these two polymers suggests a possible differentiation of biological roles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mechanism and Kinetics of Ethanol Coupling to Butanol over Hydroxyapatite

DOE PAGES

Ho, Christopher R.; Shylesh, Sankaranarayanapillai; Bell, Alexis T.

2015-12-23

The mechanism and kinetics for ethanol coupling to n-butanol over hydroxyapatite (HAP) were investigated at 573-613 K. In situ titration experiments show that the active sites for acetaldehyde and butanol formation are different. In combination with FTIR studies, it was found that ethanol dehydrogenation is catalyzed by Ca-O sites, whereas condensation of acetaldehyde is catalyzed by CaO/PO 4 3- pairs. Measurements of the reaction kinetics at various ethanol (3.5-9.4 kPa) and acetaldehyde (0.055-0.12 kPa) partial pressures reveal that direct condensation involving two ethanol molecules does not play a significant role in butanol formation; instead, n-butanol is formed via a Guerbetmore » pathway. At a constant acetaldehyde pressure, enolate formation is rate-limiting, and ethanol inhibits acetaldehyde condensation rates by competitive adsorption. A model of the reaction kinetics consistent with all experimental observations is developed.« less

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

Ho, Christopher R.; Shylesh, Sankaranarayanapillai; Bell, Alexis T.

The mechanism and kinetics for ethanol coupling to n-butanol over hydroxyapatite (HAP) were investigated at 573-613 K. In situ titration experiments show that the active sites for acetaldehyde and butanol formation are different. In combination with FTIR studies, it was found that ethanol dehydrogenation is catalyzed by Ca-O sites, whereas condensation of acetaldehyde is catalyzed by CaO/PO 4 3- pairs. Measurements of the reaction kinetics at various ethanol (3.5-9.4 kPa) and acetaldehyde (0.055-0.12 kPa) partial pressures reveal that direct condensation involving two ethanol molecules does not play a significant role in butanol formation; instead, n-butanol is formed via a Guerbetmore » pathway. At a constant acetaldehyde pressure, enolate formation is rate-limiting, and ethanol inhibits acetaldehyde condensation rates by competitive adsorption. A model of the reaction kinetics consistent with all experimental observations is developed.« less

Reversible sol-to-gel transformation of uracil gelators: specific colorimetric and fluorimetric sensor for fluoride ions.

PubMed

Xing, Ling-Bao; Yang, Bing; Wang, Xiao-Jun; Wang, Jiu-Ju; Chen, Bin; Wu, Qianhong; Peng, Hui-Xing; Zhang, Li-Ping; Tung, Chen-Ho; Wu, Li-Zhu

2013-03-05

A new type of anthracene organogelator based on uracil was obtained using organic aromatic solvents, cyclohexane, DMSO, ethanol, and ethyl acetate. It was further characterized by field-emission scanning electron microscopy and transmission electron microscopy. Specifically, the resulting organogels were demonstrated to be promising colorimetric and fluorescent sensors toward fluoride ions with high sensitivity and selectivity, accompanying the disruption of the gelators. Spectroscopic study and (1)H NMR titration experiment revealed that the deprotonation of the hydrogen atom on the N position of uracil moiety by fluoride ions is responsible for the recognition events, evidenced by immediate transformation from the sol phase to the gel state upon adding a small amount of a proton solvent, methanol. The process is reversible, with zero loss in sensing activity and sol-to-gel transformation ability even after five runs.

A high selective anion colorimetric sensor based on salicylaldehyde for fluoride in aqueous media.

PubMed

Li, Jianwei; Lin, Hai; Cai, Zunsheng; Lin, Huakuan

2009-06-01

A new and simple salicylaldehyde-based sensor 1 designed for fluoride sensing has been investigated in DMSO and even in the 9/1 DMSO/H(2)O (v/v) mixtures. The affinity constants of receptor 1 for anionic species in the 9/1 DMSO/H(2)O (v/v) reveal that it is sensitive to F. Also, the color changes induced by anions can provide a way of detection by 'naked-eye'. These result can be substantiated by the spectrum changes upon the addition of 25equiv. anions to 1 in the 9/1 DMSO/H(2)O solution. The further insights to the nature of interactions between the sensor 1 and F(-) were investigated by (1)H NMR titration experiments in 9/1 DMSO-d(6)/H(2)O (v/v). In addition, the proposed binding mode between 1 and F(-) was suggested.

Selective Nitrate Recognition by a Halogen‐Bonding Four‐Station [3]Rotaxane Molecular Shuttle

PubMed Central

Barendt, Timothy A.; Docker, Andrew; Marques, Igor; Félix, Vítor

2016-01-01

Abstract The synthesis of the first halogen bonding [3]rotaxane host system containing a bis‐iodo triazolium‐bis‐naphthalene diimide four station axle component is reported. Proton NMR anion binding titration experiments revealed the halogen bonding rotaxane is selective for nitrate over the more basic acetate, hydrogen carbonate and dihydrogen phosphate oxoanions and chloride, and exhibits enhanced recognition of anions relative to a hydrogen bonding analogue. This elaborate interlocked anion receptor functions via a novel dynamic pincer mechanism where upon nitrate anion binding, both macrocycles shuttle from the naphthalene diimide stations at the periphery of the axle to the central halogen bonding iodo‐triazolium station anion recognition sites to form a unique 1:1 stoichiometric nitrate anion–rotaxane sandwich complex. Molecular dynamics simulations carried out on the nitrate and chloride halogen bonding [3]rotaxane complexes corroborate the 1H NMR anion binding results. PMID:27436297

Exploring the mechanism of interaction between 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one and human serum albumin: Spectroscopic, calorimetric and molecular modeling studies.

PubMed

Wang, Gongke; Li, Xiang; Ding, Xuelian; Wang, Dongchao; Yan, Changling; Lu, Yan

2011-07-15

In this paper, binding interaction of 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (EMMD) with human serum albumin (HSA) under physiological conditions was investigated by using spectroscopy, isothermal titration calorimetry (ITC) and molecular modeling techniques. The results of spectroscopic studies suggested that EMMD have a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. ITC investigations indicated that drug-protein complex was stabilized by hydrophobic forces and hydrogen bonds, which was consistent with the results of molecular modeling studies. Competitive experiments indicated the displacement of warfarin by EMMD, which revealed that the binding site of EMMD to HSA was located at subdomain IIA. Copyright © 2011 Elsevier B.V. All rights reserved.

Protometric thermometric titrations of sparingly soluble compounds in water in the presence of n-octanol.

PubMed

Burgot, G; Burgot, J-L

2002-10-15

Thermometric titrimetry permits titration of acido-basic compounds in water in the presence of n-octanol. n-Octanol permits the solubilization of protolytes and moreover may also displace the equilibria of the titration reactions. Hydrochlorides of highly insoluble derivatives such as phenothiazine derivatives can be titrated with satisfactory accuracy and precision by sodium hydroxide despite their high pK(a) values. Likewise barbiturate salts can be titrated by hydrochloric acid. In the case of some salts, the methodology may permit the sequential titration of the ion and counter ion. Copyright 2002 Elsevier Science B.V.

Risks and Benefits of Rapid Clozapine Titration.

PubMed

Lochhead, Jeannie D; Nelson, Michele A; Schneider, Alan L

2016-05-18

Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS) during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

Surface acid-base properties and hydration/dehydration mechanisms of aluminum (hydr)oxides.

PubMed

Yang, Xiaofang; Sun, Zhongxi; Wang, Dongsheng; Forsling, Willis

2007-04-15

In this paper, surface physiochemical properties of three typical aluminas, gamma-Al(OH)3, gamma-Al2O3, and alpha-Al2O3, were investigated by means of XRD, SEM, TEM, BET surface area, TG/DTA, and potentiometric titration techniques. Based on the titration data, surface protonation and deprotonation constants were determined using the constant capacitance model (CCM). The emphasis of this research was laid on the comparison of the crystal structure, surface hydration/dehydration and acid-base properties of these three typical alumina minerals. The calculation results revealed that the surface acidity of the aluminas is in the order of alpha-Al2O3>gamma-Al(OH)3>gamma-Al2O3 after being hydrated for 1 h. The correlation between the hydration/dehydration mechanisms of alumina and its acid/base properties is discussed.

Synthesis of a zinc(II) complex with hexadentate N4S2 donor thioether ligand: X-ray structure, DNA binding study and DFT computation

NASA Astrophysics Data System (ADS)

Mondal, Apurba Sau; Jana, Mahendra Sekhar; Manna, Chandan Kumar; Naskar, Rahul; Mondal, Tapan Kumar

2018-07-01

A new zinc(II) complex, [Zn(L)](ClO4) with hexadentate N4S2 donor azo-thioether ligand (HL) was synthesized and characterized by several spectroscopic techniques. The structure was confirmed by single crystal X-ray analysis. The interaction of the complex with CT DNA was investigated by UV-vis method and binding constant is found to be 6.6 × 104 M-1. Competitive binding titration with ethidium bromide (EB) by fluorescence titration method reveals that the complex efficiently displaces EB from EB-DNA system and the Stern-Volmer dynamic quenching constant, Ksv is found to be 2.6 × 104 M-1. DFT and TDDFT calculations were carried out to interpret the electronic structure and electronic spectra of the complex.

Ultrasensitivity by Molecular Titration in Spatially Propagating Enzymatic Reactions

PubMed Central

Semenov, Sergey N.; Markvoort, Albert J.; Gevers, Wouter B.L.; Piruska, Aigars; de Greef, Tom F.A.; Huck, Wilhelm T.S.

2013-01-01

Delineating design principles of biological systems by reconstitution of purified components offers a platform to gauge the influence of critical physicochemical parameters on minimal biological systems of reduced complexity. Here we unravel the effect of strong reversible inhibitors on the spatiotemporal propagation of enzymatic reactions in a confined environment in vitro. We use micropatterned, enzyme-laden agarose gels which are stamped on polyacrylamide films containing immobilized substrates and reversible inhibitors. Quantitative fluorescence imaging combined with detailed numerical simulations of the reaction-diffusion process reveal that a shallow gradient of enzyme is converted into a steep product gradient by addition of strong inhibitors, consistent with a mathematical model of molecular titration. The results confirm that ultrasensitive and threshold effects at the molecular level can convert a graded input signal to a steep spatial response at macroscopic length scales. PMID:23972857

Biosorption of metal ions from aqueous solutions

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

Chen, Jiaping; Yiacoumi, Sotira

1997-01-01

Copper biosorption from aqueous solutions by calcium alginate is reported in this paper. The experimental section includes potentiometric titrations of biosorbents, batch equilibrium and kinetic studies of copper biosorption, as well as fixed-bed biosorption experiments. The potentiometric titration results show that the surface charge increases with decreasing pH. The biosorption of copper strongly depends on solution pH; the metal ion binding increases from 0 to 90 percent in pH ranging from 1.5 to 5.0. In addition, a decrease in ionic strength results in an increase of copper ion removal. Kinetic studies indicate that mass transfer plays an important role inmore » the biosorption rate. Furthermore, a fixed-bed biosorption experiment shows that calcium alginate has a significant capacity for copper ion removal. The two-pK Basic Stem model successfully represents the surface charge and equilibrium biosorption experimental data. The calculation results demonstrate that the copper removal may result from the binding of free copper and its hydroxide with surface functional groups of the biosorbents.« less

"Why not stoichiometry" versus "Stoichiometry--why not?" Part II: GATES in context with redox systems.

PubMed

Michałowska-Kaczmarczyk, Anna Maria; Asuero, Agustin G; Toporek, Marcin; Michałowski, Tadeusz

2015-01-01

Redox equilibria and titration play an important role in chemical analysis, and the formulation of an accurate mathematical description is a challenge. This article is devoted to static and (mainly) dynamic redox systems; the dynamic systems are represented by redox titrations. An overview addresses earlier approaches to static redox systems (redox diagram plots, including Pourbaix diagrams) and to titration redox systems, thereby covering a gap in the literature. After this short review, the generalized approach to electrolytic systems (GATES) is introduced, with generalized electron balance (GEB) as its inherent part within GATES/GEB. Computer simulation, performed according to GATES/GEB, enables following the changes in potential and pH of the solution, together with chemical speciation at each step of a titration, thus providing better insight into this procedure. The undeniable advantages of GATES/GEB over earlier approaches are indicated. Formulation of GEB according to two approaches (I and II) is presented on the respective examples. A general criterion distinguishing between non-redox and redox systems is presented. It is indicated that the formulation of GEB according to Approach II does not need the knowledge of oxidation degrees of particular elements; knowledge of the composition, expressed by chemical formula of the species and its charge, is sufficient for this purpose. Approach I to GEB, known also as the "short" version of GEB, is applicable if oxidation degrees for all elements of the system are known beforehand. The roles of oxidants and reductants are not ascribed to particular components forming a system and to the species thus formed. This is the complete opposite of earlier approaches to redox titrations, based on the stoichiometric redox reaction, formulated for this purpose. GEB, perceived as a law of matter conservation, is fully compatible with other (charge and concentration) balances related to the system in question. The applicability of GATES/GEB in optimization a priori of chemical analyses made with use of redox titration is indicated. The article is illustrated with many examples of static and dynamic redox systems. The related plots are obtained from calculations made according to iterative computer programs. This way, GATES/GEB enables seeing details invisible in real experiments.

A mRNA-Responsive G-Quadruplex-Based Drug Release System

PubMed Central

Yaku, Hidenobu; Murashima, Takashi; Miyoshi, Daisuke; Sugimoto, Naoki

2015-01-01

G-quadruplex-based drug delivery carriers (GDDCs) were designed to capture and release a telomerase inhibitor in response to a target mRNA. Hybridization between a loop on the GDDC structure and the mRNA should cause the G-quadruplex structure of the GDDC to unfold and release the bound inhibitor, anionic copper(II) phthalocyanine (CuAPC). As a proof of concept, GDDCs were designed with a 10-30-mer loop, which can hybridize with a target sequence in epidermal growth factor receptor (EGFR) mRNA. Structural analysis using circular dichroism (CD) spectroscopy showed that the GDDCs form a (3 + 1) type G-quadruplex structure in 100 mM KCl and 10 mM MgCl2 in the absence of the target RNA. Visible absorbance titration experiments showed that the GDDCs bind to CuAPC with Ka values of 1.5 × 105 to 5.9 × 105 M−1 (Kd values of 6.7 to 1.7 μM) at 25 °C, depending on the loop length. Fluorescence titration further showed that the G-quadruplex structure unfolds upon binding to the target RNA with Ka values above 1.0 × 108 M−1 (Kd values below 0.01 μM) at 25 °C. These results suggest the carrier can sense and bind to the target RNA, which should result in release of the bound drug. Finally, visible absorbance titration experiments demonstrated that the GDDC release CuAPC in response to the target RNA. PMID:25905703

Signal processing with a summing operational amplifier in multicomponent potentiometric titrations.

PubMed

Parczewski, A

1987-06-01

It has been proved that application of two indicator electrodes connected to the ordinary titration apparatus through an auxiliary electronic device (a summing operational amplifier) significantly extends the scope of multicomponent potentiometric titrations in which the analytes are determined simultaneously from a single titration curve. For each analyte there is a corresponding potential jump on the titration curve. By application of the proposed auxiliary device, the sum of the electrode potentials is measured. The device also enables the relative sizes of the potential jumps at the end-points on the titration curve to be varied. The advantages of the proposed signal processing are exemplified by complexometric potentiometric titrations of Fe(III) and Cu(II) in mixtures, with a platinum electrode and a copper ion-selective electrode as the indicator electrodes.

Insights into optimal basal insulin titration in type 2 diabetes: Results of a quantitative survey.

PubMed

Berard, Lori; Bonnemaire, Mireille; Mical, Marie; Edelman, Steve

2018-02-01

Basal insulin (BI) treatment initiation and dose titration in type 2 diabetes (T2DM) are often delayed. Such "clinical inertia" results in poor glycaemic control and high risk of long-term complications. This survey aimed to determine healthcare professional (HCP) and patient attitudes to BI initiation and titration. An online survey (July-August 2015) including HCPs and patients with T2DM in the USA, France and Germany. Patients were ≥18 years old and had been on BI for 6 to 36 months, or discontinued BI within the previous 12 months. Participants comprised 386 HCPs and 318 people with T2DM. While >75% of HCPs reported discussing titration at the initiation visit, only 16% to 28% of patients remembered such discussions, many (32%-42%) were unaware of the need to titrate BI, and only 28% to 39% recalled mention of the time needed to reach glycaemic goals. Most HCPs and patients agreed that more effective support tools to assist BI initiation/titration are needed; patients indicated that provision of such tools would increase confidence in self-titration. HCPs identified fear of hypoglycaemia, failure to titrate in the absence of symptoms, and low patient motivation as important titration barriers. In contrast, patients identified weight gain, the perception that titration meant worsening disease, frustration over the time to reach HbA1c goals and fear of hypoglycaemia as major factors. A disconnect exists between HCP- and patient-perceived barriers to effective BI titration. To optimize titration, strategies should be targeted to improve HCP-patient communication, and provide support and educational tools. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Insights into optimal basal insulin titration in type 2 diabetes: Results of a quantitative survey

PubMed Central

Bonnemaire, Mireille; Mical, Marie; Edelman, Steve

2017-01-01

Aims Basal insulin (BI) treatment initiation and dose titration in type 2 diabetes (T2DM) are often delayed. Such “clinical inertia” results in poor glycaemic control and high risk of long‐term complications. This survey aimed to determine healthcare professional (HCP) and patient attitudes to BI initiation and titration. Methods An online survey (July–August 2015) including HCPs and patients with T2DM in the USA, France and Germany. Patients were ≥18 years old and had been on BI for 6 to 36 months, or discontinued BI within the previous 12 months. Results Participants comprised 386 HCPs and 318 people with T2DM. While >75% of HCPs reported discussing titration at the initiation visit, only 16% to 28% of patients remembered such discussions, many (32%–42%) were unaware of the need to titrate BI, and only 28% to 39% recalled mention of the time needed to reach glycaemic goals. Most HCPs and patients agreed that more effective support tools to assist BI initiation/titration are needed; patients indicated that provision of such tools would increase confidence in self‐titration. HCPs identified fear of hypoglycaemia, failure to titrate in the absence of symptoms, and low patient motivation as important titration barriers. In contrast, patients identified weight gain, the perception that titration meant worsening disease, frustration over the time to reach HbA1c goals and fear of hypoglycaemia as major factors. Conclusion A disconnect exists between HCP‐ and patient‐perceived barriers to effective BI titration. To optimize titration, strategies should be targeted to improve HCP–patient communication, and provide support and educational tools. PMID:28719066

Thermodynamic Effects of Noncoded and Coded Methionine Substitutions in Calmodulin

PubMed Central

Yamniuk, Aaron P.; Ishida, Hiroaki; Lippert, Dustin; Vogel, Hans J.

2009-01-01

The methionine residues in the calcium (Ca2+) regulatory protein calmodulin (CaM) are structurally and functionally important. They are buried within the N- and C-domains of apo-CaM but become solvent-exposed in Ca2+-CaM, where they interact with numerous target proteins. Previous structural studies have shown that methionine substitutions to the noncoded amino acids selenomethionine, ethionine, or norleucine, or mutation to leucine do not impact the main chain structure of CaM. Here we used differential scanning calorimetry to show that these substitutions enhance the stability of both domains, with the largest increase in melting temperature (19–26°C) achieved with leucine or norleucine in the apo-C-domain. Nuclear magnetic resonance spectroscopy experiments also revealed the loss of a slow conformational exchange process in the Leu-substituted apo-C-domain. In addition, isothermal titration calorimetry experiments revealed considerable changes in the enthalpy and entropy of target binding to apo-CaM and Ca2+-CaM, but the free energy of binding was largely unaffected due to enthalpy-entropy compensation. Collectively, these results demonstrate that noncoded and coded methionine substitutions can be accommodated in CaM because of the structural plasticity of the protein. However, adjustments in side-chain packing and dynamics lead to significant differences in protein stability and the thermodynamics of target binding. PMID:19217866

Two classes of cholesterol binding sites for the β2AR revealed by thermostability and NMR.

PubMed

Gater, Deborah L; Saurel, Olivier; Iordanov, Iordan; Liu, Wei; Cherezov, Vadim; Milon, Alain

2014-11-18

Cholesterol binding to G protein-coupled receptors (GPCRs) and modulation of their activities in membranes is a fundamental issue for understanding their function. Despite the identification of cholesterol binding sites in high-resolution x-ray structures of the ?2 adrenergic receptor (β2AR) and other GPCRs, the binding affinity of cholesterol for this receptor and exchange rates between the free and bound cholesterol remain unknown. In this study we report the existence of two classes of cholesterol binding sites in β2AR. By analyzing the β2AR unfolding temperature in lipidic cubic phase (LCP) as a function of cholesterol concentration we observed high-affinity cooperative binding of cholesterol with sub-nM affinity constant. In contrast, saturation transfer difference (STD) NMR experiments revealed the existence of a second class of cholesterol binding sites, in fast exchange on the STD NMR timescale. Titration of the STD signal as a function of cholesterol concentration provided a lower limit of 100 mM for their dissociation constant. However, these binding sites are specific for both cholesterol and β2AR, as shown with control experiments using ergosterol and a control membrane protein (KpOmpA). We postulate that this specificity is mediated by the high-affinity bound cholesterol molecules and propose the formation of transient cholesterol clusters around the high-affinity binding sites.

Efficient analysis of stochastic gene dynamics in the non-adiabatic regime using piecewise deterministic Markov processes

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

Lin, Yen Ting; Buchler, Nicolas E.

Single-cell experiments show that gene expression is stochastic and bursty, a feature that can emerge from slow switching between promoter states with different activities. In addition to slow chromatin and/or DNA looping dynamics, one source of long-lived promoter states is the slow binding and unbinding kinetics of transcription factors to promoters, i.e. the non-adiabatic binding regime. Here, we introduce a simple analytical framework, known as a piecewise deterministic Markov process (PDMP), that accurately describes the stochastic dynamics of gene expression in the non-adiabatic regime. We illustrate the utility of the PDMP on a non-trivial dynamical system by analysing the propertiesmore » of a titration-based oscillator in the non-adiabatic limit. We first show how to transform the underlying chemical master equation into a PDMP where the slow transitions between promoter states are stochastic, but whose rates depend upon the faster deterministic dynamics of the transcription factors regulated by these promoters. We show that the PDMP accurately describes the observed periods of stochastic cycles in activator and repressor-based titration oscillators. We then generalize our PDMP analysis to more complicated versions of titration-based oscillators to explain how multiple binding sites lengthen the period and improve coherence. Finally, we show how noise-induced oscillation previously observed in a titration-based oscillator arises from non-adiabatic and discrete binding events at the promoter site.« less

Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis

PubMed Central

Bello, Alfonso E; Perkins, Elizabeth L; Jay, Randy; Efthimiou, Petros

2017-01-01

Methotrexate (MTX) remains the cornerstone therapy for patients with rheumatoid arthritis (RA), with well-established safety and efficacy profiles and support in international guidelines. Clinical and radiologic results indicate benefits of MTX monotherapy and combination with other agents, yet patients may not receive optimal dosing, duration, or route of administration to maximize their response to this drug. This review highlights best practices for MTX use in RA patients. First, to improve the response to oral MTX, a high initial dose should be administered followed by rapid titration. Importantly, this approach does not appear to compromise safety or tolerability for patients. Treatment with oral MTX, with appropriate dose titration, then should be continued for at least 6 months (as long as the patient experiences some response to treatment within 3 months) to achieve an accurate assessment of treatment efficacy. If oral MTX treatment fails due to intolerability or inadequate response, the patient may be “rescued” by switching to subcutaneous delivery of MTX. Consideration should also be given to starting with subcutaneous MTX given its favorable bioavailability and pharmacodynamic profile over oral delivery. Either initiation of subcutaneous MTX therapy or switching from oral to subcutaneous administration improves persistence with treatment. Upon transition from oral to subcutaneous delivery, MTX dosage should be maintained, rather than increased, and titration should be performed as needed. Similarly, if another RA treatment is necessary to control the disease, the MTX dosage and route of administration should be maintained, with titration as needed. PMID:28435338

Efficient analysis of stochastic gene dynamics in the non-adiabatic regime using piecewise deterministic Markov processes

DOE PAGES

Lin, Yen Ting; Buchler, Nicolas E.

2018-01-31

Single-cell experiments show that gene expression is stochastic and bursty, a feature that can emerge from slow switching between promoter states with different activities. In addition to slow chromatin and/or DNA looping dynamics, one source of long-lived promoter states is the slow binding and unbinding kinetics of transcription factors to promoters, i.e. the non-adiabatic binding regime. Here, we introduce a simple analytical framework, known as a piecewise deterministic Markov process (PDMP), that accurately describes the stochastic dynamics of gene expression in the non-adiabatic regime. We illustrate the utility of the PDMP on a non-trivial dynamical system by analysing the propertiesmore » of a titration-based oscillator in the non-adiabatic limit. We first show how to transform the underlying chemical master equation into a PDMP where the slow transitions between promoter states are stochastic, but whose rates depend upon the faster deterministic dynamics of the transcription factors regulated by these promoters. We show that the PDMP accurately describes the observed periods of stochastic cycles in activator and repressor-based titration oscillators. We then generalize our PDMP analysis to more complicated versions of titration-based oscillators to explain how multiple binding sites lengthen the period and improve coherence. Finally, we show how noise-induced oscillation previously observed in a titration-based oscillator arises from non-adiabatic and discrete binding events at the promoter site.« less

Resorcarene-based receptor: versatile behavior in its interaction with heavy and soft metal cations.

PubMed

Danil de Namor, Angela F; Chaaban, Jinane K; Piro, Oscar E; Castellano, Eduardo E

2006-02-09

Standard solution Gibbs energies, DeltasG degrees, of the resorcarene-based receptor 5,11,17,23-ethylthiomethylated calix[4]resorcarene, (characterized by 1H NMR and X-ray diffraction studies) in its monomeric state (established through partition experiments) in various solvents are for the first time reported in the area of resorcarene chemistry. Transfer Gibbs energies of from hexane (reference solvent) to other medium are calculated. Agreement between DeltatG degrees (referred to the pure solvents) and standard partition Gibbs energies, DeltapG degrees (solvent mutually saturated) is found. Cation-ligand interactions were investigated through 1H NMR (CD3CN and CD3OD) and conductometric titrations in acetonitrile and methanol. 1H NMR data revealed the sites of interaction of with the metal cation. The composition of the metal-ion complexes (Ag+ and Pb2+ in acetonitrile and Ag+ and Cu2+ in methanol) was established through conductometric titrations. Thus, complexes of 1:1 stoichiometry were formed between and Ag+ and Pb2+ in acetonitrile and Cu2+ in methanol. However, in moving from acetonitrile to methanol, the composition of the silver complex was altered. Thus, two metal cations are hosted by a unit of the ligand. As far as Cu2+ and in acetonitrile is concerned, conductance data suggest that metalates are formed in which up to four units of Cu2+ are taken up per unit of resorcarene. The contrasting behavior of with Cu2+ in acetonitrile relative to methanol is discussed. As far as mercury (II) is concerned, the unusual jump in conductance observed in the titration of Hg2+ with in acetonitrile and methanol after the formation of a multicharged complex (undefined composition) is attributed to the presence of highly charged smaller units (higher mobility) resulting from the departure of pendant arms from the resorcarene backbone. Isolation of these species followed by X-ray diffraction studies corroborated this statement. The thermodynamic characterization of metal-ion complexes of Ag+ and Pb2+ in acetonitrile and Cu2+ and Ag+ in methanol is reported. Final conclusions are given.

Rapid Clozapine Titration in Patients with Treatment Refractory Schizophrenia.

PubMed

Poyraz, Cana Aksoy; Özdemir, Armağan; Sağlam, Nazife Gamze Usta; Turan, Şenol; Poyraz, Burç Çağrı; Tomruk, Nesrin; Duran, Alaattin

2016-06-01

The aim of this study is to evaluate the safety and effectiveness of rapid clozapine titration in patients with schizophrenia in hospital settings. We conducted a retrospective two-center cohort study to compare the safety and effectiveness of clozapine with different titration rates in treatment-refractory patients with schizophrenia. In the first center, clozapine was started at 25-50 mg followed by 50-100 mg as needed every 6 h on day 1, followed by increases of 50-100 mg/day. In the second center, titration was slower; clozapine initiated with 12.5-50 mg on day 1 followed by increases of 25-50 mg/day. The number of days between starting of clozapine until discharge was shorter in the rapid titration group (22.4 ± 8.72 vs 27.0 ± 10.5, p = 0.1). Number of days of total hospital stay were significantly shorter in the rapid titration group (29.6 ± 10.6 vs 41.2 ± 14.8, p = 0.002). Hypotension was more common in the rapid titration group and one patient had suspected myocarditis. Rapid clozapine titration appeared safe and effective. The length of stay following initiation of clozapine was shorter in the rapid-titration group, although this was not statistically significant. However starting clozapine earlier together with rapid titration has significantly shortened the length of hospital stay in patients with treatment refractory schizophrenia.

Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.

PubMed

Biton, Victor; Gil-Nagel, Antonio; Brodie, Martin J; Derossett, Sarah E; Nohria, Virinder

2013-11-01

Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated potassium-channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p=0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG. Copyright © 2013 Elsevier B.V. All rights reserved.

40 CFR Appendix A to Part 425 - Potassium Ferricyanide Titration Method

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Potassium Ferricyanide Titration..., App. A Appendix A to Part 425—Potassium Ferricyanide Titration Method Source The potassium... buffered sulfide solution is titrated with standard potassium ferricyanide solution in the presence of a...

40 CFR Appendix A to Part 425 - Potassium Ferricyanide Titration Method

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Potassium Ferricyanide Titration..., App. A Appendix A to Part 425—Potassium Ferricyanide Titration Method Source The potassium... buffered sulfide solution is titrated with standard potassium ferricyanide solution in the presence of a...

Scopolamine Effects Under a Titrating-Delayed-Nonmatching-to-Position Procedure

ERIC Educational Resources Information Center

Porritt, M.; Poling, A.

2008-01-01

In a study of working memory, the performance of rats under titrating-delayed-nonmatching- to-position (TDNMTP) procedures was examined. Overall accuracy and the number of trials completed were inversely related to titration value, whereas the highest delay attained was directly related to titration value. When given intraperitoneally,…

Chemical composition and organoleptic evaluation of juice from steamed cashew apple blended with orange juice.

PubMed

Inyang, U E; Abah, U J

1997-01-01

Fully riped cashew apples (yellow variety) were steamed for 7 minutes prior to juice extraction. The extracted juice was blended with various proportions of sweet orange juice. Chemical composition and organoleptic evaluation were carried out on both the blended and unblended juices. The ascorbic acid content of unsteamed cashew apple juice was 287 mg/100 ml. Steaming of the cashew apple prior to juice extraction resulted in a decreased (230 mg/100 ml) content of ascorbic acid. It also led to slight decreases in soluble solids and titratable acidity. A comparison of the chemical composition of the two juices showed that the orange juice contained more sugars, titratable acidity and soluble solids but less ascorbic acid than cashew apple juice. Consequently, the soluble solids, titratable acidity, reducing and total sugars of the blends increased with increase in the proportions of orange juice while the content of ascorbic acid was decreasing. In spite of the decrease in ascorbic acid content of the blends, results showed that blended juice would no doubt be a very good source of ascorbic acid. Result of the organoleptic evaluation revealed that a 60% cashew apple and 40% orange juice gave a good quality juice in terms of flavor, after taste and overall acceptability.

Dopant titrating ion mobility spectrometry for trace exhaled nitric oxide detection.

PubMed

Peng, Liying; Hua, Lei; Li, Enyou; Wang, Weiguo; Zhou, Qinghua; Wang, Xin; Wang, Changsong; Li, Jinghua; Li, Haiyang

2015-01-05

Ion mobility spectrometry (IMS) is a promising non-invasive tool for the analysis of exhaled gas and exhaled nitric oxide (NO), a biomarker for diagnosis of respiratory diseases. However, the high moisture in exhaled gas always brings about extra overlapping ion peaks and results in poor identification ability. In this paper, p-benzoquinone (PBQ) was introduced into IMS to eliminate the interference of overlapping ion peaks and realize the selective identification of NO. The overlapping ions caused by moisture were titrated by PBQ and then converted to hydrated PBQ anions (C6H4[Formula: see text](H2O)n). The NO concentration could be determined by quantifying gas phase hydrated nitrite anions (N[Formula: see text](H2O)n), product ions of NO. Under optimized conditions, a limit of detection (LOD) of about 1.4 ppbv and a linear range of 10-200 ppbv were obtained for NO even in 100% relative humidity (RH) purified air. Furthermore, this established method was applied to measure hourly the exhaled NO of eight healthy volunteers, and real-time monitoring the exhaled NO of an esophageal carcinoma patient during radical surgery. These results revealed the potential of the current dopant titrating IMS method in the measurement of exhaled NO for medical disease diagnosis.

Synthesis, structure, DNA/protein binding, and cytotoxic activity of a rhodium(III) complex with 2,6-bis(2-benzimidazolyl)pyridine.

PubMed

Esteghamat-Panah, Roya; Hadadzadeh, Hassan; Farrokhpour, Hossein; Simpson, Jim; Abdolmaleki, Amir; Abyar, Fatemeh

2017-02-15

A new mononuclear rhodium(III) complex, [Rh(bzimpy)Cl 3 ] (bzimpy = 2,6-bis(2-benzimidazolyl)pyridine), was synthesized and characterized by elemental analysis and spectroscopic methods. The molecular structure of the complex was confirmed by single-crystal X-ray crystallography. The interaction of the complex with fish sperm DNA (FS-DNA) was investigated by UV spectroscopy, emission titration, and viscosity measurement in order to evaluate the possible DNA-binding mode and to calculate the corresponding DNA-binding constant. The results reveal that the Rh(III) complex interacts with DNA through groove binding mode with a binding affinity on the order of 10 4 . In addition, the binding of the Rh(III) complex to bovine serum albumin (BSA) was monitored by UV-Vis and fluorescence emission spectroscopy at different temperatures. The mechanism of the complex interaction was found to be static quenching. The thermodynamic parameters (ΔH, ΔS, and ΔG) obtained from the fluorescence spectroscopy data show that van der Waals interactions and hydrogen bonds play a major role in the binding of the Rh(III) complex to BSA. For the comparison of the DNA- and BSA-binding affinities of the free bzimpy ligand with its Rh(III) complex, the absorbance titration and fluorescence quenching experiments of the free bzimpy ligand with DNA and BSA were carried out. Competitive experiments using eosin Y and ibuprofen as site markers indicated that the complex was mainly located in the hydrophobic cavity of site I of the protein. These experimental results were confirmed by the results of molecular docking. Finally, the in vitro cytotoxicity properties of the Rh(III) complex against the MCF-7, K562, and HT-29 cell lines were evaluated and compared with those of the free ligand (bzimpy). It was found that the complexation process improved the anticancer activity significantly. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Titration Curves: Fact and Fiction.

ERIC Educational Resources Information Center

Chamberlain, John

1997-01-01

Discusses ways in which datalogging equipment can enable titration curves to be measured accurately and how computing power can be used to predict the shape of curves. Highlights include sources of error, use of spreadsheets to generate titration curves, titration of a weak acid with a strong alkali, dibasic acids, weak acid and weak base, and…

Natural monocrystalline pyrite as a sensor in non-aqueous solution Part I: Potentiometric titration of weak acids in, N,N-dimethylformamide, methylpyrrolidone and pyridine.

PubMed

Mihajlović, Lj V; Mihajlović, R P; Antonijević, M M; Vukanović, B V

2004-11-15

The possibility of applying natural monocrystaline pyrite as a sensor for the potentiometric titration of weak acids in N,N-dimethylformamide, methylpyrrolidone and pyridine was investigated. The potential of this electrode in N,N-dimethylformamide, methylpyrrolidone and pyridine exhibits a sub-Nernst dependence. In N,N-dimethylformamide the slope (mV/pH) is 39.0 and in methylpyrrolidone it is 45.0. The potential jumps at the titration end-point obtained in the titration of weak acids are higher than those obtained by the application of a glass electrode as the indicator electrode The potential in the course of the titration and at the titration end-point (TEP) are rapidly established. Sodium methylate, potassium hydroxide and tetrabutylammonium hydroxide (TBAH) proved to be very suitable titrating agents for these titrations. The results obtained in the determination of the investigated weak acids deviate by 0.1-0.35% with respect to those obtained by using a glass electrode as the indicator electrode.

EFFECTS OF PH, SOLID/SOLUTION RATIO, IONIC STRENGTH, AND ORGANIC ACIDS ON PB AND CD SOPRTION ON KAOLINITE

EPA Science Inventory

Potentiometric and ion-selective electrode titrations together with batch sorption/desorption experiments, were performed to explain the aqueous and surface complexation reactions between kaolinite, Pb, Cd and three organic acids. Variables included pH, ionic strength, metal conc...

Determination of Ammonia in Household Cleaners: An Instrumental Analysis Experiment.

ERIC Educational Resources Information Center

Graham, Richard C.; DePew, Steven

1983-01-01

Briefly discusses three techniques for assessing amount of ammonia present in household cleaners. Because of disadvantages with these methods, the thermometric titration technique is suggested in which students judge the best buy based on relative cost of ammonia present in samples. Laboratory procedures, typical results, and reactions involved…

Homemade Equipment for the Teaching of Electrochemistry at Advanced Level. Part II.

ERIC Educational Resources Information Center

Chan, K. M.

1985-01-01

Provides a detailed description for the construction of equipment needed to investigate acid/base equilibria through the measurement of pH and potentiometric titrations. Suggested experiments and calibration techniques are explained. This information helps to solve the problems of inadequate, expensive equipment required for A-level chemistry…

Potentiometric titration of metal ions in ethanol.

PubMed

Gibson, Graham T T; Mohamed, Mark F; Neverov, Alexei A; Brown, R S

2006-09-18

The potentiometric titrations of Zn2+, Cu2+ and 12 Ln3+ metal ions were obtained in ethanol to determine the titration constants (defined as the at which the [-OEt]/[Mx+]t ratios are 0.5, 1.5, and 2.5) and in two cases (La3+ and Zn2+) a complete speciation diagram. Several simple monobasic acids and aminium ions were also titrated to test the validity of experimental titration measurements and to establish new constants in this medium that will be useful for the preparation of buffers and standard solutions. The dependence of the titration constants on the concentration and type of metal ion and specific counterion effects is discussed. In selected cases, the titration profiles were analyzed using a commercially available fitting program to obtain information about the species present in solution, including La3+ for which a dimer model is proposed. The fitting provides the microscopic values for deprotonation of one to four metal-bound ethanol molecules. Kinetics for the La3+-catalyzed ethanolysis of paraoxon as a function of are presented and analyzed in terms of La3+ speciation as determined by the analysis of potentiometric titration curves. The stability constants for the formation of Zn2+ and Cu2+ complexes with 1,5,9-triazacyclododecane as determined by potentiometric titration are presented.

Molecular Dynamics Simulation of the Titration of Polyoxocations in Aqueous Solution

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

Rustad, James R.

The aqueous complex ion Al30O8(OH)56(H2O)26 18+(Al30) has a variety of bridging and terminal amphoteric surface functional groups which deprotonate over a pH range of 4–7. Their relative degree of protonation is calculated here from a series of molecular dynamics simulations in what appear to be the first molecular dynamics simulations of an acidometric titration. In these simulations, a model M30O8(OH)56(H2O)26 18+ ion is embedded in aqueous solution and titrated with hydroxide ions in the presence of a charge-compensating background of perchlorate ions. Comparison with titration of a model M13O4(OH)24(H2O)12 7+ reveals that the M30 ion is more acidic than themore » M13 ion due to the presence of acidic nH2O functional groups. The higher acidities of the functional groups on the M30 ion appear to result from enhanced hydration. Metal–oxygen bond lengths are calculated for the ion in solution, an isolated ion in the gas phase, and in its crystalline hydrate sulfate salt. Gas-phase and crystalline bond lengths do not correlate well with those calculated in solution. The acidities do not relate in any simple way to the number of metals coordinating the surface functional group or the M-O bond length. Moreover, the calculated acidity in solution does not correlate with proton affinities calculated for the isolated ion in the absence of solvent. It is concluded that the search for simple indicators of structure–reactivity relationships at the level of individual reactive sites faces major limitations, unless specific information on the hydration states of the functional groups is available.« less

Evaluation on the use of cerium in the NBL Titrimetric Method

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

Zebrowski, J.P.; Orlowicz, G.J.; Johnson, K.D.

An alternative to potassium dichromate as titrant in the New Brunswick Laboratory Titrimetric Method for uranium analysis was sought since chromium in the waste makes disposal difficult. Substitution of a ceric-based titrant was statistically evaluated. Analysis of the data indicated statistically equivalent precisions for the two methods, but a significant overall bias of +0.035% for the ceric titrant procedure. The cause of the bias was investigated, alterations to the procedure were made, and a second statistical study was performed. This second study revealed no statistically significant bias, nor any analyst-to-analyst variation in the ceric titration procedure. A statistically significant day-to-daymore » variation was detected, but this was physically small (0.01 5%) and was only detected because of the within-day precision of the method. The added mean and standard deviation of the %RD for a single measurement was found to be 0.031%. A comparison with quality control blind dichromate titration data again indicated similar overall precision. Effects of ten elements on the ceric titration`s performance was determined. Co, Ti, Cu, Ni, Na, Mg, Gd, Zn, Cd, and Cr in previous work at NBL these impurities did not interfere with the potassium dichromate titrant. This study indicated similar results for the ceric titrant, with the exception of Ti. All the elements (excluding Ti and Cr), caused no statistically significant bias in uranium measurements at levels of 10 mg impurity per 20-40 mg uranium. The presence of Ti was found to cause a bias of {minus}0.05%; this is attributed to the presence of sulfate ions, resulting in precipitation of titanium sulfate and occlusion of uranium. A negative bias of 0.012% was also statistically observed in the samples containing chromium impurities.« less

Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects

PubMed Central

Legangneux, Eric; Gardin, Anne; Johns, Donald

2013-01-01

Aim Previous studies have shown transient decreases in heart rate (HR) following administration of sphingosine 1‐phosphate (S1P) receptor modulators including BAF312. This study was conducted to determine whether dose titration of BAF312 reduces or eliminates these effects. Methods Fifty‐six healthy subjects were randomized 1:1:1:1 to receive BAF312 in one of two dose titration (DT) regimens (DT1 and DT2: 0.25–10 mg over 9–10 days), no titration (10 mg starting dose) or placebo. Pharmacodynamic and pharmacokinetic parameters were assessed. Results Neither DT1 nor DT2 resulted in clinically significant bradycardia or atrioventricular conduction effects. Both titration regimens showed a favourable difference on each of days 1–12 vs. the non‐titration regimen on day 1 for HR effects (P < 0.0001). On day 1, the geometric mean ratio of the fraction from the previous day in minimum daily HR between DT1 and non‐titration was 1.18 (95% confidence interval [CI] 1.13, 1.23) and 1.14 (95% CI 1.09, 1.18) for DT2 (both P < 0.05) with significant differences noted through to day 12. Non‐titration HRs showed considerable separation from placebo throughout the study. There was no statistically significant reduction in HR vs. placebo on day 1 in either titration regimen. On days 3–7 subjects in DT1 and DT2 experienced minor reductions in HR vs. placebo (approximately 5 beats min−1; P ≤ 0.0001). From days 9–12, HRs in both titration regimens were comparable with placebo. Conclusion Both titration regimens effectively attenuated the initial bradyarrhythmia observed on day 1 of treatment with BAF312 10 mg. PMID:22845008

Comparison of VFA titration procedures used for monitoring the biogas process.

PubMed

Lützhøft, Hans-Christian Holten; Boe, Kanokwan; Fang, Cheng; Angelidaki, Irini

2014-05-01

Titrimetric determination of volatile fatty acids (VFAs) contents is a common way to monitor a biogas process. However, digested manure from co-digestion biogas plants has a complex matrix with high concentrations of interfering components, resulting in varying results when using different titration procedures. Currently, no standardized procedure is used and it is therefore difficult to compare the performance among plants. The aim of this study was to evaluate four titration procedures (for determination of VFA-levels of digested manure samples) and compare results with gas chromatographic (GC) analysis. Two of the procedures are commonly used in biogas plants and two are discussed in literature. The results showed that the optimal titration results were obtained when 40 mL of four times diluted digested manure was gently stirred (200 rpm). Results from samples with different VFA concentrations (1-11 g/L) showed linear correlation between titration results and GC measurements. However, determination of VFA by titration generally overestimated the VFA contents compared with GC measurements when samples had low VFA concentrations, i.e. around 1 g/L. The accuracy of titration increased when samples had high VFA concentrations, i.e. around 5 g/L. It was further found that the studied ionisable interfering components had lowest effect on titration when the sample had high VFA concentration. In contrast, bicarbonate, phosphate and lactate had significant effect on titration accuracy at low VFA concentration. An extended 5-point titration procedure with pH correction was best to handle interferences from bicarbonate, phosphate and lactate at low VFA concentrations. Contrary, the simplest titration procedure with only two pH end-points showed the highest accuracy among all titration procedures at high VFA concentrations. All in all, if the composition of the digested manure sample is not known, the procedure with only two pH end-points should be the procedure of choice, due to its simplicity and accuracy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Temperature effect on the acid-base behaviour of Na-montmorillonite.

PubMed

Duc, Myriam; Carteret, Cédric; Thomas, Fabien; Gaboriaud, Fabien

2008-11-15

We report a study of the acid-base properties of Na-montmorillonite suspensions at temperatures from 25 degrees C to 80 degrees C, by continuous and batch potentiometric methods, combined with analysis of the dissolved and readsorbed species. The batch titration curves reveal that the dissolution processes of Na-montmorillonite and silica-rich secondary phases are increasingly predominant, respectively at acid and basic pH, and according to the temperature. The continuous titration curves are less affected by these side reactions. In the absence of a common intersection point, the thermodynamic analysis of the curves was based on the shift of the PZNPC with the ionic strength. This shift was not significantly altered by the temperature, by comparison with the dissociation product of water in the same conditions. Therefore we concluded that protonation-deprotonation of the dissociable sites at the edges of the clay platelets is not significantly temperature dependent.

Simple quantification of surface carboxylic acids on chemically oxidized multi-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Gong, Hyejin; Kim, Seong-Taek; Lee, Jong Doo; Yim, Sanggyu

2013-02-01

The surface of multi-walled carbon nanotube (MWCNT) was chemically oxidized using nitric acid and sulfuric-nitric acid mixtures. Thermogravimetric analysis, transmission electron microscopy and infrared spectroscopy revealed that the use of acid mixtures led to higher degree of oxidation. More quantitative identification of surface carboxylic acids was carried out using X-ray photoelectron spectroscopy (XPS) and acid-base titration. However, these techniques are costly and require very long analysis times to promptly respond to the extent of the reaction. We propose a much simpler method using pH measurements and pre-determined pKa value in order to estimate the concentration of carboxylic acids on the oxidized MWCNT surfaces. The results from this technique were consistent with those obtained from XPS and titration, and it is expected that this simple quantification method can provide a cheap and fast way to monitor and control the oxidation reaction of MWCNT.

Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial.

PubMed

Rini, Brian I; Melichar, Bohuslav; Ueda, Takeshi; Grünwald, Viktor; Fishman, Mayer N; Arranz, José A; Bair, Angel H; Pithavala, Yazdi K; Andrews, Glen I; Pavlov, Dmitri; Kim, Sinil; Jonasch, Eric

2013-11-01

Population pharmacokinetic data suggest axitinib plasma exposure correlates with efficacy in metastatic renal-cell carcinoma. Axitinib dose titration might optimise exposure and improve outcomes. We prospectively assessed the efficacy and safety of axitinib dose titration in previously untreated patients with metastatic renal-cell carcinoma. In this randomised, double-blind, multicentre, phase 2 study, patients were enrolled from 49 hospitals and outpatient clinics in the Czech Republic, Germany, Japan, Russia, Spain, and USA. Patients with treatment-naive metastatic renal-cell carcinoma received axitinib 5 mg twice daily during a 4 week lead-in period. Those patients with blood pressure 150/90 mm Hg or lower, no grade 3 or 4 treatment-related toxic effects, no dose reductions, and no more than two antihypertensive drugs for 2 consecutive weeks were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1), and then randomly assigned (1:1) to either masked titration with axitinib to total twice daily doses of 7 mg, and then 10 mg, if tolerated, or placebo titration. Patients who did not meet these criteria continued without titration. The primary objective was comparison of the proportion of patients achieving an objective response between randomised groups. Safety analyses were based on all patients who received at least one dose of axitinib. Between Sept 2, 2009, and Feb 28, 2011, we enrolled 213 patients, of whom 112 were randomly assigned to either the axitinib titration group (56 patients) or the placebo titration group (56 patients). 91 were not eligible for titration, and ten withdrew during the lead-in period. 30 patients (54%, 95% CI 40-67) in the axitinib titration group had an objective response, as did 19 patients (34%, 22-48]) in the placebo titration group (one-sided p=0·019). 54 (59%, 95% CI 49-70) of non-randomised patients achieved an objective response. Common grade 3 or worse, all-causality adverse events in treated patients were hypertension (ten [18%] of 56 in the axitinib titration group vs five [9%] of 56 in the placebo titration group vs 45 [49%] of 91 in the non-randomised group), diarrhoea (seven [13%] vs two [4%] vs eight [9%]), and decreased weight (four [7%] vs three [5%] vs six [7%]). One or more all-causality serious adverse events were reported in 15 (27%) patients in the axitinib titration group, 13 (23%) patients in the placebo titration group, and 35 (38%) non-randomised patients. The most common serious adverse events in all 213 patients were disease progression and dehydration (eight each [4%]), and diarrhoea, vomiting, pneumonia, and decreased appetite (four each [2%]). The greater proportion of patients in the axitinib titration group achieving an objective response supports the concept of individual axitinib dose titration in selected patients with metastatic renal-cell carcinoma. Axitinib shows clinical activity with a manageable safety profile in treatment-naive patients with this disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

DIFFERENTIAL THERMOMETRIC TITRATIONS AND THE DETERMINATION OF HEATS OF REACTION,

DTIC Science & Technology

TITRATION , THERMISTORS), (*HEAT OF REACTION, TITRATION ), SILVER COMPOUNDS, NITRATES, AMMONIA, PYRIDINES, ETHYLENEDIAMINE, AMINES, ALCOHOLS, BUTANOLS, PROPANOLS, SODIUM COMPOUNDS, HYDROXIDES, TEST METHODS

Towards the elucidation of molecular determinants of cooperativity in the liver bile acid binding protein.

PubMed

Pedò, Massimo; D'Onofrio, Mariapina; Ferranti, Pasquale; Molinari, Henriette; Assfalg, Michael

2009-11-15

Bile acid binding proteins (BABPs) are cytosolic lipid chaperones contributing to the maintenance of bile acid homeostasis and functional distribution within the cell. Liver BABPs act in parallel with ileal transporters to ensure vectorial transport of bile salts in hepatocytes and enterocytes, respectively. We describe the investigation of ligand binding to liver BABP, an essential step in the understanding of intracellular bile salt transport. Binding site occupancies were monitored in NMR titration experiments using (15)N-labelled ligand, while the relative populations of differently bound BABP forms were assessed by mass spectrometry. This site-specific information allowed the determination of intrinsic thermodynamic parameters and the identification of an extremely high cooperativity between two binding sites. Protein-observed NMR experiments revealed a global structural rearrangement which suggests an allosteric mechanism at the basis of the observed cooperativity. The view of a molecular tool capable of buffering against significant concentrations of free bile salts in a large range of solution conditions emerges from the observed pH-dependence of binding. We set to determine the molecular determinants of cooperativity by analysing the binding properties of a protein containing a mutated internal histidine. Both mass spectrometry and NMR experiments are consistent with an overall decreased binding affinity of the mutant, while the measured diffusion coefficients of ligand species reveal that the affinity loss concerns essentially one of the two binding sites. We therefore identified a mutation able to disrupt energetic communication functional to efficient binding and conclude that the buried histidine establishes contacts that stabilize the ternary complex. 2009 Wiley-Liss, Inc.

ITC-derived binding affinity may be biased due to titrant (nano)-aggregation. Binding of halogenated benzotriazoles to the catalytic domain of human protein kinase CK2

PubMed Central

Winiewska, Maria; Bugajska, Ewa

2017-01-01

The binding of four bromobenzotriazoles to the catalytic subunit of human protein kinase CK2 was assessed by two complementary methods: Microscale Thermophoresis (MST) and Isothermal Titration Calorimetry (ITC). New algorithm proposed for the global analysis of MST pseudo-titration data enabled reliable determination of binding affinities for two distinct sites, a relatively strong one with the Kd of the order of 100 nM and a substantially weaker one (Kd > 1 μM). The affinities for the strong binding site determined for the same protein-ligand systems using ITC were in most cases approximately 10-fold underestimated. The discrepancy was assigned directly to the kinetics of ligand nano-aggregates decay occurring upon injection of the concentrated ligand solution to the protein sample. The binding affinities determined in the reverse ITC experiment, in which ligands were titrated with a concentrated protein solution, agreed with the MST-derived data. Our analysis suggests that some ITC-derived Kd values, routinely reported together with PDB structures of protein-ligand complexes, may be biased due to the uncontrolled ligand (nano)-aggregation, which may occur even substantially below the solubility limit. PMID:28273138

Calcium ion binding to a soil fulvic acid using a donnan potential model

USGS Publications Warehouse

Marinsky, J.A.; Mathuthu, A.; Ephraim, J.H.; Reddy, M.M.

1999-01-01

Calcium ion binding to a soil fulvic acid (Armadale Bh Horizon) was evaluated over a range of calcium ion concentrations, from pH 3.8 to 7.3, using potentiometric titrations and calcium ion electrode measurements. Fulvic acid concentration was constant (100 milligrams per liter) and calcium ion concentration varied up to 8 X 10-4 moles per liter. Experiments discussed here included: (1) titrations of fulvic acid-calcium ion containing solutions with sodium hydroxide; and (2) titrations of fully neutralized fulvic acid with calcium chloride solutions. Apparent binding constants (expressed as the logarithm of the value, log ??app) vary with solution pH, calcium ion concentration, degree of acid dissociation, and ionic strength (from log ??app = 2.5 to 3.9) and are similar to those reported by others. Fulvic acid charge, and the associated Donnan Potential, influences calcium ion-fulvic acid ion pair formation. A Donnan Potential corrrection term allowed calculation of intrinsic calcium ion-fulvic acid binding constants. Intrinsic binding constants vary from 1.2 to 2.5 (the average value is about log??= 1.6) and are similar to, but somewhat higher than, stability constants for calcium ion-carboxylic acid monodentate complexes. ?? by Oldenbourg Wissenschaftsverlag, Mu??nchen.

Determination of carbonate carbon in geological materials by coulometric titration

USGS Publications Warehouse

Engleman, E.E.; Jackson, L.L.; Norton, D.R.

1985-01-01

A coulometric titration is used for the determination of carbonate carbon in geological materials. Carbon dioxide is evolved from the sample by the addition of 2 M perchloric acid, with heating, and is determined by automated coulometric titration. The coulometric titration showed improved speed and precision with comparable accuracy to gravimetric and gasometric techniques. ?? 1985.

Simple Modification of Karl-Fischer Titration Method for Determination of Water Content in Colored Samples

PubMed Central

Tavčar, Eva; Turk, Erika; Kreft, Samo

2012-01-01

The most commonly used technique for water content determination is Karl-Fischer titration with electrometric detection, requiring specialized equipment. When appropriate equipment is not available, the method can be performed through visual detection of a titration endpoint, which does not enable an analysis of colored samples. Here, we developed a method with spectrophotometric detection of a titration endpoint, appropriate for moisture determination of colored samples. The reaction takes place in a sealed 4 ml cuvette. Detection is performed at 520 nm. Titration endpoint is determined from the graph of absorbance plotted against titration volume. The method has appropriate reproducibility (RSD = 4.3%), accuracy, and linearity (R 2 = 0.997). PMID:22567558

Highly sensitive and selective detection of Al(III) ions in aqueous buffered solution with fluorescent peptide-based sensor.

PubMed

In, Byunggyu; Hwang, Gi Won; Lee, Keun-Hyeung

2016-09-15

A fluorescent sensor based on a tripeptide (SerGluGlu) with a dansyl fluorophore detected selectively Al(III) among 16 metal ions in aqueous buffered solutions without any organic cosolvent. The peptide-based sensor showed a highly sensitive turn on response to aluminium ion with high binding affinity (1.84×10(4)M(-1)) in aqueous buffered solutions. The detection limit (230nM, 5.98ppb) of the peptide-based sensor was much lower than the maximum allowable level (7.41μM) of aluminium ions in drinking water demanded by EPA. The binding mode of the peptide sensor with aluminium ions was characterized using ESI mass spectrometry, NMR titration, and pH titration experiments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Implementation of a pharmacist-managed heart failure medication titration clinic.

PubMed

Martinez, Amanda S; Saef, Jerold; Paszczuk, Anna; Bhatt-Chugani, Hetal

2013-06-15

The development, implementation, and initial results of a pharmacist-managed heart failure (HF) medication titration clinic are described. In a quality-improvement initiative at a Veterans Affairs health care system, clinical pharmacists were incorporated into the hospital system's interprofessional outpatient HF clinic. In addition, a separate pharmacist-managed HF medication titration clinic was established, in which pharmacists were granted an advanced scope of practice and prescribing privileges, enabling them to initiate and adjust medication dosages under specific protocols jointly established by cardiology and pharmacy staff. Pharmacists involved in the titration clinic tracked patients' daily body weight, vital signs, and volume status using telephone-monitoring technology and via patient interviews. A retrospective chart review comparing achievement of target doses of angiotensin-converting enzyme inhibitor (ACEI), angiotensin-receptor blocker (ARB), and β-blocker therapies in a group of patients (n = 28) whose dosage titrations were carried out by nurses or physicians prior to implementation of the pharmacist-managed HF medication titration clinic and a group of patients (n = 27) enrolled in the medication titration clinic during its first six months of operation indicated that target ACEI and ARB doses were achieved in a significantly higher percentage of pharmacist-managed titration clinic enrollees (52.9% versus 31%, p = 0.007). Patients enrolled in the pharmacist-managed HF medication titration clinic also had a significantly higher rate of attainment of optimal β-blocker doses (49% versus 24.7%, p = 0.012). Implementation of a pharmacist-managed HF medication titration clinic increased the percentage of patients achieving optimal ACEI, ARB, and β-blocker dosages.

Titrating the Cost of Plant Toxins Against Predators: a Case Study with Common Duikers, Sylvicapra grimmia.

PubMed

Abu Baker, Mohammad A

2015-10-01

Foragers face many variables that influence their food intake. These may include habitat structure, time, climate, resource characteristic, food quality, and plant defenses. I conducted foraging experiments using common duikers that involved: 1) testing the effect of plant toxins on foraging, and 2) titrating toxin intake against safety. I used giving up densities (GUDs, food remaining after foraging) to test for selection among trays containing alfalfa pellets treated with water, with 10% oxalic acid, or 10% quebracho tannin. Pairs of trays were placed within islands of woody vegetation and out in open grass. I also conducted a titration experiment by offering the duikers a choice between a patch with water-treated pellets placed at a risky site, or a patch with one of three oxalic acid-treated pellets at a safe site. This made it possible to determine the concentration of oxalic acid at which the cost of toxin in the safe site equals the predation cost at the risky site. The common duikers showed no selectivity among the three treatments at 10% concentration, however, GUDs in the open grass (i.e., safe) were significantly lower than in the wooded islands (i.e., risky). As the oxalic acid concentration increased at the safe sites, the duiker's food intake from the risky sites increased significantly. The results demonstrate that foraging hazards may come in different forms such as predation and plant toxins, and their interactions may alter habitat use, foraging patterns, and perceptions of risk. These variables occur under natural situations, altering the overall habitat quality.

The Polybasic Region of the Polysialyltransferase ST8Sia-IV Binds Directly to the Neural Cell Adhesion Molecule, NCAM.

PubMed

Bhide, Gaurang P; Prehna, Gerd; Ramirez, Benjamin E; Colley, Karen J

2017-03-14

Polysialic acid (polySia) is a unique post-translational modification found on a small set of mammalian glycoproteins. Composed of long chains of α2,8-linked sialic acid, this large, negatively charged polymer attenuates protein and cell adhesion and modulates signaling mediated by its carriers and proteins that interact with these carriers. PolySia is crucial for the proper development of the nervous system and is upregulated during tissue regeneration and in highly invasive cancers. Our laboratory has previously shown that the neural cell adhesion molecule, NCAM, has an acidic surface patch in its first fibronectin type III repeat (FN1) that is critical for the polysialylation of N-glycans on the adjacent immunoglobulin domain (Ig5). We have also identified a polysialyltransferase (polyST) polybasic region (PBR) that may mediate substrate recognition. However, a direct interaction between the NCAM FN1 acidic patch and the polyST PBR has yet to be demonstrated. Here, we have probed this interaction using isothermal titration calorimetry and nuclear magnetic resonance (NMR) spectroscopy. We observe direct and specific binding between FN1 and the PBR peptide that is dependent upon acidic residues in FN1 and basic residues of the PBR. NMR titration experiments verified the role of the FN1 acidic patch in the recognition of the PBR and suggest a conformational change of the Ig5-FN1 linker region following binding of the PBR to the acidic patch. Finally, mutation of residues identified by NMR titration experiments impacts NCAM polysialylation, supporting their mechanistic role in protein-specific polysialylation.

Thermometric titration of cadmium with sodium diethyldithiocarbamate, with oxidation by hydrogen peroxide as indicator reaction.

PubMed

Hattori, T; Yoshida, H

1987-08-01

A new method of end-point indication is described for thermometric titration of cadmium with sodium diethyldithiocarbamate (DDTC). It is based on the redox reaction between hydrogen peroxide added to the system before titration, and the first excess of DDTC. Amounts of cadmium in the range 10-50 mumoles are titrated within 1% error.

Tracer-monitored flow titrations.

PubMed

Sasaki, Milton K; Rocha, Diogo L; Rocha, Fábio R P; Zagatto, Elias A G

2016-01-01

The feasibility of implementing tracer-monitored titrations in a flow system is demonstrated. A dye tracer is used to estimate the instant sample and titrant volumetric fractions without the need for volume, mass or peak width measurements. The approach was applied to spectrophotometric flow titrations involving variations of sample and titrant flow-rates (i.e. triangle programmed technique) or concentration gradients established along the sample zone (i.e. flow injection system). Both strategies required simultaneous monitoring of two absorbing species, namely the titration indicator and the dye tracer. Mixing conditions were improved by placing a chamber with mechanical stirring in the analytical path aiming at to minimize diffusional effects. Unlike most of flow-based titrations, the innovation is considered as a true titration, as it does not require a calibration curve thus complying with IUPAC definition. As an application, acidity evaluation in vinegars involving titration with sodium hydroxide was selected. Phenolphthalein and brilliant blue FCF were used as indicator and dye tracer, respectively. Effects of sample volume, titrand/titrant concentrations and flow rates were investigated aiming at improved accuracy and precision. Results were reliable and in agreement with those obtained by a reference titration procedure. Copyright © 2015 Elsevier B.V. All rights reserved.

Determination of quaternary ammonium compounds by potentiometric titration with an ionic surfactant electrode: single-laboratory validation.

PubMed

Price, Randi; Wan, Ping

2010-01-01

A potentiometric titration for determining the quaternary ammonium compounds (QAC) commonly found in antimicrobial products was validated by a single laboratory. Traditionally, QACs were determined by using a biphasic (chloroform and water) manual titration procedure. Because of safety considerations regarding chloroform, as well as the subjectivity of color indicator-based manual titration determinations, an automatic potentiometric titration procedure was tested with quaternary nitrogen product formulations. By using the Metrohm Titrando system coupled with an ionic surfactant electrode and an Ag/AgCl reference electrode, titrations were performed with various QAC-containing formulation products/matrixes; a standard sodium lauryl sulfate solution was used as the titrant. Results for the products tested are sufficiently reproducible and accurate for the purpose of regulatory product enforcement. The robustness of the method was measured by varying pH levels, as well as by comparing buffered versus unbuffered titration systems. A quantitation range of 1-1000 ppm quaternary nitrogen was established. Eight commercially available antimicrobial products covering a variety of matrixes were assayed; the results obtained were comparable to those obtained by the manual titration method. Recoveries of 94 to 104% were obtained for spiked samples.

Comparison of the clinical outcomes between unattended home APAP and polysomnography manual titration in obstructive sleep apnea patients.

PubMed

Wongsritrang, Krongthong; Fueangkamloon, Sumet

2013-09-01

To compare the clinical outcomes and determine the difference in therapeutic pressure between Automatic positive airway pressure (APAP) and polysomnography manual titration. Fifty patients of obstructive sleep apnea (OSA), moderate to severe cases, were randomized into two groups of intervention: 95-percentile pressure derived from APAP titration and an optimal pressure derived from manual titration. Clinical outcomes were assessed before and after four weeks. The average 95-percentile pressure derived from APAP titration was 11.7 +/- 0.3 cmH2O with median mask leak 1.3 L/min. The average optimal pressure derived from manual titration was 8.2 +/- 0.3 cmH2O. Pearson correlation analysis showed weak positive correlation (r = 0.336, p = 0.017). The Epworth Sleepiness Score (ESS), Quality of life tests: PSQI (Pittsburg Sleep Quality Index), and SF-36 (Medical Outcomes Study 36-Item Short-Form Health Survey) were improved significantly in both groups, but there were no statistical significant differences between groups. An APAP titration is an effective method of pressure determination for conventional CPAP therapy and shows no difference in clinical outcomes comparing the standard titration.

A Protocol Analysis of the Influence of Technology on Students' Actions, Verbal Commentary, and Thought Processes During the Performance of Acid-Base Titrations.

ERIC Educational Resources Information Center

Nakhleh, Mary B.; Krajcik, Joseph S.

1993-01-01

From an analysis of 14 secondary student's actions and thought processes, it was found that technology's level of information affected the focus of student observations. The microcomputer group focused primarily on the graph while other groups exhibited multiple foci. The discussion data also reveal that students have three main ideas about how…

A multicenter experience with generic tacrolimus conversion.

PubMed

McDevitt-Potter, Lisa M; Sadaka, Basma; Tichy, Eric M; Rogers, Christin C; Gabardi, Steven

2011-09-27

The first generic tacrolimus product gained Food and Drug Administration approval in August 2009. This prospective, observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus. Transplant recipients on stable tacrolimus doses were converted from brand to generic tacrolimus on a mg:mg basis. Data were collected at the time of generic conversion (study arm) and at a time point exactly 6 months before conversion (control arm) for all subjects. Seventy conversions from four centers are reported. Subjects were a mean of 70 months after kidney (n=37), liver (n=28), or multiorgan (n=5) transplant. In the study arm, mean tacrolimus doses were 4.4 and 4.5 mg/d and mean tacrolimus trough concentrations were 5.8 and 5.9 ng/mL before and after conversion, respectively. In the control arm, mean tacrolimus doses were 4.6 and 4.6 mg/d and mean tacrolimus trough concentrations were 6.1 and 5.9 ng/mL before and after the control time point, respectively. Dose titrations occurred in five patients (7%) in the control arm and 15 patients (21%) in the study arm (P=0.028). Mean monthly drug costs were $645 for brand, $593 for generic, and $595 for generic after dose titrations. Mean monthly patient copays were $38 for brand and $15 for generic. These cumulative data show that dose requirements and trough levels are similar between brand and generic tacrolimus and that generic substitution allows for savings. However, postconversion monitoring is prudent as patients may require dose titration.

Non-damaging laser therapy of the macula: Titration algorithm and tissue response

NASA Astrophysics Data System (ADS)

Palanker, Daniel; Lavinsky, Daniel; Dalal, Roopa; Huie, Philip

2014-02-01

Retinal photocoagulation typically results in permanent scarring and scotomata, which limit its applicability to the macula, preclude treatments in the fovea, and restrict the retreatments. Non-damaging approaches to laser therapy have been tested in the past, but the lack of reliable titration and slow treatment paradigms limited their clinical use. We developed and tested a titration algorithm for sub-visible and non-damaging treatments of the retina with pulses sufficiently short to be used with pattern laser scanning. The algorithm based on Arrhenius model of tissue damage optimizes the power and duration for every energy level, relative to the threshold of lesion visibility established during titration (and defined as 100%). Experiments with pigmented rabbits established that lesions in the 50-75% energy range were invisible ophthalmoscopically, but detectable with Fluorescein Angiography and OCT, while at 30% energy there was only very minor damage to the RPE, which recovered within a few days. Patients with Diabetic Macular Edema (DME) and Central Serous Retinopathy (CSR) have been treated over the edematous areas at 30% energy, using 200μm spots with 0.25 diameter spacing. No signs of laser damage have been detected with any imaging modality. In CSR patients, subretinal fluid resolved within 45 days. In DME patients the edema decreased by approximately 150μm over 60 days. After 3-4 months some patients presented with recurrence of edema, and they responded well to retreatment with the same parameters, without any clinically visible damage. This pilot data indicates a possibility of effective and repeatable macular laser therapy below the tissue damage threshold.

Macromolecular Competition Titration Method: Accessing Thermodynamics of the Unmodified Macromolecule–Ligand Interactions Through Spectroscopic Titrations of Fluorescent Analogs

PubMed Central

Bujalowski, Wlodzimierz; Jezewska, Maria J.

2011-01-01

Analysis of thermodynamically rigorous binding isotherms provides fundamental information about the energetics of the ligand–macromolecule interactions and often an invaluable insight about the structure of the formed complexes. The Macromolecular Competition Titration (MCT) method enables one to quantitatively obtain interaction parameters of protein–nucleic acid interactions, which may not be available by other methods, particularly for the unmodified long polymer lattices and specific nucleic acid substrates, if the binding is not accompanied by adequate spectroscopic signal changes. The method can be applied using different fluorescent nucleic acids or fluorophores, although the etheno-derivatives of nucleic acid are especially suitable as they are relatively easy to prepare, have significant blue fluorescence, their excitation band lies far from the protein absorption spectrum, and the modification eliminates the possibility of base pairing with other nucleic acids. The MCT method is not limited to the specific size of the reference nucleic acid. Particularly, a simple analysis of the competition titration experiments is described in which the fluorescent, short fragment of nucleic acid, spanning the exact site-size of the protein–nucleic acid complex, and binding with only a 1:1 stoichiometry to the protein, is used as a reference macromolecule. Although the MCT method is predominantly discussed as applied to studying protein–nucleic acid interactions, it can generally be applied to any ligand–macromolecule system by monitoring the association reaction using the spectroscopic signal originating from the reference macromolecule in the presence of the competing macromolecule, whose interaction parameters with the ligand are to be determined. PMID:21195223

Charge characteristics of humic and fulvic acids: comparative analysis by colloid titration and potentiometric titration with continuous pK-distribution function model.

PubMed

Bratskaya, S; Golikov, A; Lutsenko, T; Nesterova, O; Dudarchik, V

2008-09-01

Charge characteristics of humic and fulvic acids of a different origin (inshore soils, peat, marine sediments, and soil (lysimetric) waters) were evaluated by means of two alternative methods - colloid titration and potentiometric titration. In order to elucidate possible limitations of the colloid titration as an express method of analysis of low content of humic substances we monitored changes in acid-base properties and charge densities of humic substances with soil depth, fractionation, and origin. We have shown that both factors - strength of acidic groups and molecular weight distribution in humic and fulvic acids - can affect the reliability of colloid titration. Due to deviations from 1:1 stoichiometry in interactions of humic substances with polymeric cationic titrant, the colloid titration can underestimate total acidity (charge density) of humic substances with domination of weak acidic functional groups (pK>6) and high content of the fractions with molecular weight below 1kDa.

Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial

PubMed Central

Rini, Brian I; Melichar, Bohuslav; Ueda, Takeshi; GrÜnwald, Viktor; Fishman, Mayer N; Arranz, José A; Bair, Angel H; Pithavala, Yazdi K; Andrews, Glen I; Pavlov, Dmitri; Kim, Sinil; Jonasch, Eric

2014-01-01

Summary Background Population pharmacokinetic data suggest axitinib plasma exposure correlates with efficacy in metastatic renal-cell carcinoma. Axitinib dose titration might optimise exposure and improve outcomes. We prospectively assessed the efficacy and safety of axitinib dose titration in previously untreated patients with metastatic renal-cell carcinoma. Methods In this randomised, double-blind, multicentre, phase 2 study, patients were enrolled from 49 hospitals and outpatient clinics in the Czech Republic, Germany, Japan, Russia, Spain, and USA. Patients with treatment-naive metastatic renal-cell carcinoma received axitinib 5 mg twice daily during a 4 week lead-in period. Those patients with blood pressure 150/90 mm Hg or lower, no grade 3 or 4 treatment-related toxic effects, no dose reductions, and no more than two antihypertensive drugs for 2 consecutive weeks were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1), and then randomly assigned (1:1) to either masked titration with axitinib to total twice daily doses of 7 mg, and then 10 mg, if tolerated, or placebo titration. Patients who did not meet these criteria continued without titration. The primary objective was comparison of the proportion of patients achieving an objective response between randomised groups. Safety analyses were based on all patients who received at least one dose of axitinib. This ongoing trial is registered with ClinicalTrials.gov, number NCT00835978. Findings Between Sept 2, 2009, and Feb 28, 2011, we enrolled 213 patients, of whom 112 were randomly assigned to either the axitinib titration group (56 patients) or the placebo titration group (56 patients). 91 were not eligible for titration, and ten withdrew during the lead-in period. 30 patients (54%, 95% CI 40–67) in the axitinib titration group had an objective response, as did 19 patients (34%, 22–48]) in the placebo titration group (one-sided p=0·019). 54 (59%, 95% CI 49–70) of non-randomised patients achieved an objective response. Common grade 3 or worse, all-causality adverse events in treated patients were hypertension (ten [18%] of 56 in the axitinib titration group vs five [9%] of 56 in the placebo titration group vs 45 [49%] of 91 in the non-randomised group), diarrhoea (seven [13%] vs two [4%] vs eight [9%]), and decreased weight (four [7%] vs three [5%] vs six [7%]). One or more all-causality serious adverse events were reported in 15 (27%) patients in the axitinib titration group, 13 (23%) patients in the placebo titration group, and 35 (38%) non-randomised patients. The most common serious adverse events in all 213 patients were disease progression and dehydration (eight each [4%]), and diarrhoea, vomiting, pneumonia, and decreased appetite (four each [2%]). Interpretation The greater proportion of patients in the axitinib titration group achieving an objective response supports the concept of individual axitinib dose titration in selected patients with metastatic renal-cell carcinoma. Axitinib shows clinical activity with a manageable safety profile in treatment-naive patients with this disease. Funding Pfizer Inc. PMID:24140184

Titration Techniques

NASA Astrophysics Data System (ADS)

Jacobsen, Jerrold J.; Houston Jetzer, Kelly; Patani, Néha; Zimmerman, John; Zweerink, Gerald

1995-07-01

Significant attention is paid to the proper technique for reading a meniscus. Video shows meniscus-viewing techniques for colorless and dark liquids and the consequences of not reading a meniscus at eye level. Lessons are provided on approaching the end point, focusing on end point colors produced via different commonly used indicators. The concept of a titration curve is illustrated by means of a pH meter. Carefully recorded images of the entire range of meniscus values in a buret, pipet, and graduated cylinder are included so that you can show your students, in lecture or pre-lab discussion, any meniscus and discuss how to read the buret properly. These buret meniscus values are very carefully recorded at the rate of one video frame per hundredth of a milliliter, so that an image showing any given meniscus value can be obtained. These images can be easily incorporated into a computer-based multimedia environment for testing or meniscus-reading exercises. Two of the authors have used this technique and found the exercise to be very well received by their students. Video on side two shows nearly 100 "bloopers", demonstrating both the right way and wrong ways to do tasks associated with titration. This material can be used in a variety of situations: to show students the correct way to do something; to test students by asking them "What is this person doing wrong?"; or to develop multimedia, computer-based lessons. The contents of Titration Techniques are listed below: Side 1 Titration: what it is. A simple titration; Acid-base titration animation; A brief redox titration; Redox titration animation; A complete acid-base titration. Titration techniques. Hand technique variations; Stopcock; Using a buret to measure liquid volumes; Wait before reading meniscus; Dirty and clean burets; Read meniscus at eye level (see Fig. 1); Meniscus viewing techniques--light colored liquids; Meniscus viewing techniques--dark liquids; Using a magnetic stirrer; Rough titration; Significant figures; Approaching the end point; End point colors; Titration with a pH meter; Titration curves; Colors of indicators. Meniscus values. Buret meniscus values; Pipet meniscus values; Graduated cylinder meniscus values. Side 2"Bloopers". Introducing the people; Titration animation; Inspecting the buret; Rinsing the buret with water; Preparing a solid sample; Obtaining a liquid sample; Delivering a liquid sample with a Mohr pipet; Pipetting a liquid sample with a Mohr pipet; Rinsing the Mohr pipet with sample; Using the Mohr pipet to transfer sample; Delivering a liquid sample with a volumetric pipet; Pipetting a liquid sample with a volumetric pipet; Rinsing the volumetric pipet with sample; Using the volumetric pipet to transfer sample; Obtaining the titrant; Rinsing the buret with titrant; Filling the buret with titrant; Adding the indicator; The initial reading; Beginning the titration; Delivering titrant; The final reading. Figure 3. Near the end point a single drop of titrant can cause a lasting color change.

Determination of Sulfate by Conductometric Titration: An Undergraduate Laboratory Experiment

ERIC Educational Resources Information Center

Garcia, Jennifer; Schultz, Linda D.

2016-01-01

The classic technique for sulfate analysis in an undergraduate quantitative analysis lab involves precipitation as the barium salt with barium chloride, collection of the precipitate by gravity filtration using ashless filter paper, and removal of the filter paper by charring over a Bunsen burner. The entire process is time-consuming, hazardous,…

Identification of Weak Acids and Bases by Titration with Primary Standards. A Modern Version of an Old Analytical Chemistry Experiment.

ERIC Educational Resources Information Center

Thompson, Robert Q.

1988-01-01

Describes a laboratory exercise in which acid dissociation constants and molecular weights are extracted from sample data and the sample is identified. Emphasizes accurate volumetric work while bringing to practice the concepts of acid-base equilibria, activity coefficients, and thermodynamic constants. (CW)

Organic Analyses in Water Quality Control Programs. Training Manual.

ERIC Educational Resources Information Center

Office of Water Program Operations (EPA), Cincinnati, OH. National Training and Operational Technology Center.

This document is a lecture/laboratory manual dealing with the analysis of selected organic pollutants. It is intended for use by those having little or no experience in the field, but having one year (or equivalent) of college organic chemistry, and having basic laboratory skills (volumetric glassware, titration, analytical and trip balances).…

Kinetics of Ethyl Acetate Synthesis Catalyzed by Acidic Resins

ERIC Educational Resources Information Center

Antunes, Bruno M.; Cardoso, Simao P.; Silva, Carlos M.; Portugal, Ines

2011-01-01

A low-cost experiment to carry out the second-order reversible reaction of acetic acid esterification with ethanol to produce ethyl acetate is presented to illustrate concepts of kinetics and reactor modeling. The reaction is performed in a batch reactor, and the acetic acid concentration is measured by acid-base titration versus time. The…

Changes in Acidity, TSS, and Sugar Content at Different Storage Periods of the Postharvest Mango (Mangifera indica L.) Influenced by Bavistin DF

PubMed Central

Islam, Md. Khairul; Khan, M. Z. H.; Sarkar, M. A. R.; Absar, Nurul; Sarkar, S. K.

2013-01-01

A detailed study was carried out with the postharvest mangoes (namely, the Langra and the Khirshapat) treated with different levels of Bavistin DF (BDF) solution (namely, 250, 500, and 750 ppm) for obtaining results on biochemical changes as well as storability of postharvest mango. The experiment was laid out in randomized complete block design with three replicates. The results of the experiments exhibited that only the single effect of varieties was found to be significant in most of the parameters studied. The Langra enriched a greater quantity of titratable acidity and total soluble solid (TSS) at 3rd day, over the Khirshapat. On the other hand, Khirshapat showed increased pulp pH and TSS at all the storage duration. The results explored that some physicochemical properties, namely, pulp pH, TSS, sugar (total, reducing, and nonreducing), and titratable acidity along with shelf life drastically decreased from untreated mangoes. Bavistin DF with the doses of 750 ppm showed better results in delaying the changes in physicochemical properties and extended shelf life. PMID:26904616

Initial Evaluation of a Titration Appliance for Temporary Treatment of Obstructive Sleep Apnea.

PubMed

Levendowski, Daniel J; Morgan, Todd; Westbrook, Philip

2012-01-01

Custom oral appliances that adjustably advance the mandible provide superior outcomes when treating patients with moderate or severe sleep apnea. Custom appliances, however, are expensive, must be fitted by a dentist, and the likelihood of successful outcomes are difficult to predict. An inexpensive trial appliance, if proven efficacious, might be used to predict custom appliance outcomes or to provide temporary therapeutic benefit. The aim of this initial study was to assess the treatment efficacy of a novel titration oral appliance with that of an optimized custom appliance. Seventeen patients, treated with a custom oral appliance for at least one year, successfully completed a three-night home sleep test. The baseline obstructive sleep apnea severity was established on Night 1 with seven patients exhibiting severe, six moderate and four mild apnea/hypopnea indexes. Patients were randomly assigned to wear their custom appliance or the titration appliance on Nights 2 and 3. Significant reductions in the mean overall and supine apnea indexes (p < 0.05), and the overall (p < 0.01) and supine (p < 0.05) apnea/hypopnea indexes were observed for both the titration and custom appliances. The proportion of patients who exhibited at least a 50% reduction in the overall apnea index and supine apnea/hypopnea were similar for the titration and custom appliance (~60%). The custom appliance reduced the overall apnea/hypopnea index by 50% in a greater proportion of the patients compared to the titration appliance (77% vs. 53%). The titration appliance significantly reduced the degree of hypoxic exposure across sleep disordered breathing events overall (p < 0.05) and supine (p < 0.01). Patients found their custom appliance was more comfortable than the titration appliance, but preferred the titration appliance to no therapy. The titration appliance may be useful in assessing oral appliance treatment efficacy. When set to 70% of maximum protrusion, the titration appliance may provide immediate, temporary therapeutic benefit.

Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.

PubMed

Legangneux, Eric; Gardin, Anne; Johns, Donald

2013-03-01

Previous studies have shown transient decreases in heart rate (HR) following administration of sphingosine 1-phosphate (S1P) receptor modulators including BAF312. This study was conducted to determine whether dose titration of BAF312 reduces or eliminates these effects. Fifty-six healthy subjects were randomized 1:1:1:1 to receive BAF312 in one of two dose titration (DT) regimens (DT1 and DT2: 0.25-10 mg over 9-10 days), no titration (10 mg starting dose) or placebo. Pharmacodynamic and pharmacokinetic parameters were assessed. Neither DT1 nor DT2 resulted in clinically significant bradycardia or atrioventricular conduction effects. Both titration regimens showed a favourable difference on each of days 1-12 vs. the non-titration regimen on day 1 for HR effects (P < 0.0001). On day 1, the geometric mean ratio of the fraction from the previous day in minimum daily HR between DT1 and non-titration was 1.18 (95% confidence interval [CI] 1.13, 1.23) and 1.14 (95% CI 1.09, 1.18) for DT2 (both P < 0.05) with significant differences noted through to day 12. Non-titration HRs showed considerable separation from placebo throughout the study. There was no statistically significant reduction in HR vs. placebo on day 1 in either titration regimen. On days 3-7 subjects in DT1 and DT2 experienced minor reductions in HR vs. placebo (approximately 5 beats min⁻¹; P ≤ 0.0001). From days 9-12, HRs in both titration regimens were comparable with placebo. Both titration regimens effectively attenuated the initial bradyarrhythmia observed on day 1 of treatment with BAF312 10 mg. © 2012 Novartis Institutes for BioMedical Research (NIBIR). British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Initial Evaluation of a Titration Appliance for Temporary Treatment of Obstructive Sleep Apnea

PubMed Central

Levendowski, Daniel J.; Morgan, Todd; Westbrook, Philip

2015-01-01

Background Custom oral appliances that adjustably advance the mandible provide superior outcomes when treating patients with moderate or severe sleep apnea. Custom appliances, however, are expensive, must be fitted by a dentist, and the likelihood of successful outcomes are difficult to predict. An inexpensive trial appliance, if proven efficacious, might be used to predict custom appliance outcomes or to provide temporary therapeutic benefit. Objective The aim of this initial study was to assess the treatment efficacy of a novel titration oral appliance with that of an optimized custom appliance. Methods Seventeen patients, treated with a custom oral appliance for at least one year, successfully completed a three-night home sleep test. The baseline obstructive sleep apnea severity was established on Night 1 with seven patients exhibiting severe, six moderate and four mild apnea/hypopnea indexes. Patients were randomly assigned to wear their custom appliance or the titration appliance on Nights 2 and 3. Results Significant reductions in the mean overall and supine apnea indexes (p < 0.05), and the overall (p < 0.01) and supine (p < 0.05) apnea/hypopnea indexes were observed for both the titration and custom appliances. The proportion of patients who exhibited at least a 50% reduction in the overall apnea index and supine apnea/hypopnea were similar for the titration and custom appliance (~60%). The custom appliance reduced the overall apnea/hypopnea index by 50% in a greater proportion of the patients compared to the titration appliance (77% vs. 53%). The titration appliance significantly reduced the degree of hypoxic exposure across sleep disordered breathing events overall (p < 0.05) and supine (p < 0.01). Patients found their custom appliance was more comfortable than the titration appliance, but preferred the titration appliance to no therapy. Conclusion The titration appliance may be useful in assessing oral appliance treatment efficacy. When set to 70% of maximum protrusion, the titration appliance may provide immediate, temporary therapeutic benefit. PMID:26523244

Control of OSA during automatic positive airway pressure titration in a clinical case series: predictors and accuracy of device download data.

PubMed

Huang, Hsin-Chia Carol; Hillman, David R; McArdle, Nigel

2012-09-01

To investigate the factors associated with physiologic control of obstructive sleep apnea (OSA) during automatic positive airway pressure (APAP) titration in a clinical series. To also assess the usefulness of apnea-hypopnea index (AHI) data downloaded from the APAP device (Dev AHI). Retrospective review of a consecutive series of patients with OSA who underwent APAP titration (Autoset Spirit, ResMed, Bella Vista, New South Wales, Australia ) with simultaneous polysomnographic (PSG) monitoring in the sleep laboratory. Tertiary sleep clinic. There were 190 consecutive patients with OSA referred for APAP titration. There were 58% of patients who achieved optimal or good control of OSA (titration PSG AHI < 10, or at least 50% reduction in AHI if diagnostic AHI < 15/hr) during APAP titration. The independent predictors of titration PSG AHI were a history of cardiac disease and elevated central apnea and arousal indices during the diagnostic study. Although the median and interquartile range (IQR) AHI from the device (7.0, 3.9-11.6 events/hr) was only slightly less than the PSG AHI (7.8, 3.9-14.4 events/hr, P = 0.04) during titration, case-by-case agreement between the two measures was poor (chi-square < 0.001). In a clinical sample control of OSA during APAP titration is often poor, and close clinical follow-up is particularly needed in patients with a history of cardiac disease or with high arousal or central apnea indices on the diagnostic study. Device AHI does not reliably assess control during APAP titration, and PSG assessment may be required if clinical response to treatment is poor. The findings relate to the ResMed AutoSet device and may not apply to other devices.

An RCT Investigating Patient-Driven Versus Physician-Driven Titration of BIAsp 30 in Patients with Type 2 Diabetes Uncontrolled Using NPH Insulin.

PubMed

Chraibi, Abdelmjid; Al-Herz, Shoorook; Nguyen, Bich Dao; Soeatmadji, Djoko W; Shinde, Anil; Lakshmivenkataraman, Balasubramanian; Assaad-Khalil, Samir H

2017-08-01

The aim of this study was to confirm the efficacy of patient-driven titration of BIAsp 30 in terms of glycemic control, by comparing it to physician-driven titration of BIAsp 30, in patients with type 2 diabetes in North Africa, the Middle East, and Asia. A 20-week, open-label, randomized, two-armed, parallel-group, multicenter study in Egypt, Indonesia, Morocco, Saudi Arabia, and Vietnam. Patients (n = 155) with type 2 diabetes inadequately controlled using neutral protamine Hagedorn (NPH) insulin were randomized to either patient-driven or physician-driven BIAsp 30 titration. The noninferiority of patient-driven compared to physician-driven titration with respect to the reduction in HbA1c was confirmed. The estimated mean change in HbA1c from baseline to week 20 was -1.27% in the patient-driven arm and -1.04% in the physician-driven arm, with an estimated treatment difference of -0.23% (95% confidence interval: -0.54; 0.08). After 20 weeks of treatment, the proportions of patients achieving the target of HbA1c <7.5% were similar between titration arms; the proportions of patients achieving the target of ≤6.5% were also similar. Both titration algorithms were well tolerated, and hypoglycemic episode rates were similar in both arms. Patient-driven titration of BIAsp 30 can be as effective and safe as physician-driven titration in non-Western populations. Overall, the switch from NPH insulin to BIAsp 30 was well tolerated in both titration arms and led to improved glycemic control. A limitation of the study was the relatively small number of patients recruited in each country. ClinicalTrials.gov NCT01589653. Novo Nordisk A/S, Denmark.

Initiation of Levodopa-Carbidopa Intestinal Gel Infusion Using Telemedicine (Video Communication System) Facilitates Efficient and Well-Accepted Home Titration in Patients with Advanced Parkinson's Disease.

PubMed

Willows, Thomas; Dizdar, Nil; Nyholm, Dag; Widner, Håkan; Grenholm, Peter; Schmiauke, Ursula; Urbom, Anna; Groth, Kristina; Larsson, Jörgen; Permert, Johan; Kjellander, Susanna

2017-01-01

Levodopa-carbidopa intestinal gel (LCIG; Duodopa®) is used for continuous infusion in advanced Parkinson's disease. To achieve optimal effect, the LCIG dose is individually titrated, traditionally conducted during hospitalization in Sweden. However, dose adjustment depends on surrounding conditions, physical activity, and emotional stress, which is why titration at home could be beneficial. Telemedicine (TM) using a video communication system offers alternative titration procedures, allowing LCIG initiation at home. Study objectives were to show the feasibility of TM for LCIG home titration, evaluate resource use, and assess patient, neurologist, and nurse satisfaction. Four clinics enrolled 15 patients to observe efficiency and feasibility of TM-based monitoring. Patient median (range) age was 67 (52-73) years and time since diagnosis was 10 (7-23) years. Median time between LCIG initiation and end of TM-assisted titration was 2.8 (2.0-13.8) days. Median time required for home titration by neurologists, nurses, and patients was (hours:minutes) 1 : 14 (0 : 29-1 : 52), 5 : 49 (2 : 46-10 : 3), and 8 : 53 (4 : 11-14 : 11), respectively. Neurologists and nurses considered this to be less time than required for hospital titration. TM allowed patients 92% free time from start to end of titration. Technical problems associated with TM contacts were rare, mostly related to digital link, and quickly resolved. Patients, neurologists, and nurses were satisfied using TM. No serious adverse events were reported; there was one device complaint (tube occlusion). In this study, TM-assisted LCIG titration at home was resource-efficient, technically feasible, well-accepted and was deemed satisfactory by patients, neurologists, and nurses.

Persistent benefits of slow titration of paroxetine in a six-month follow-up.

PubMed

Olgiati, Paolo; Serretti, Alessandro

2015-09-01

Paroxetine titration may be difficult in older individuals as they are more sensitive to side effects. The current study extends to 6 months our previously published report in which paroxetine was started at 2.5 mg/day and slowly increased by 2.5 mg on alternate days (slow titration) or rapidly titrated to target dose from 10 mg/day (standard titration) in a naturalistic setting. Here, the follow-up period was extended to 26 weeks. We performed an intent-to-treat analysis of 47 subjects from the original sample (major depressive disorder and/or generalized anxiety disorder (GAD); >60 years of age). Missing evaluations were replaced by last observations carried forward. GAD was included as a stratification factor. Patients in whom paroxetine was slowly up-titrated were more likely to remit (84.0% vs 54.5%; p = 0.028) and had lower core depression (p = 0.0015) and psychic anxiety levels (p = 0.006) after 26 weeks. Dropout rate was 20% in the slow titration group compared with 77.3% in the standard titration arm (p < 0.001). Patients with GAD accounted for all significant associations. No substantial differences were reported between slow and standard titration groups in the subsample without GAD. Despite some limitations, these findings suggest that paroxetine treatment should be started at lower doses in older depressed patients and slowly up-titrated. This strategy would allow to increase antidepressant response and the likelihood of completing treatment cycle in patients with high anxiety levels and GAD comorbidity. Copyright © 2015 John Wiley & Sons, Ltd.

Up-titration of allopurinol in patients with gout.

PubMed

Jennings, Claudine G; Mackenzie, Isla S; Flynn, Rob; Ford, Ian; Nuki, George; De Caterina, Raffaele; Riches, Philip L; Ralston, Stuart H; MacDonald, Thomas M

2014-08-01

European League against Rheumatism (EULAR) gout management guidelines recommend achieving a target urate level <6.0 mg/dL (<357 µmol/L). Allopurinol is the most widely used urate-lowering therapy; however, many gout patients who are prescribed allopurinol do not have urate levels optimally controlled. The objective of this analysis was to review the efficacy and tolerability of allopurinol up-titration in achieving the EULAR target levels. The Febuxostat versus Allopurinol Streamlined Trial (FAST) is an ongoing multi-centre study comparing the cardiovascular safety of febuxostat and allopurinol (target recruitment: 5706 patients). Recruited patients were already taking allopurinol and the protocol required up-titration of daily allopurinol dose, in 100 mg increments, to achieve the EULAR urate target level prior to randomisation. We reviewed pre-randomisation data from the first 400 recruited and subsequently randomised FAST patients. Of 400 patients, 144 (36%) had urate levels ≥357 µmol/L at screening and required allopurinol up-titration. Higher urate levels were significantly associated with lower allopurinol dose, male sex, increased BMI, increased alcohol intake and diuretic use. Mean fall in urate levels after a single 100-mg dose increase was 71 µmol/L. The number of up-titrations required ranged from one to five (median = 1) with 65% of patients controlled after one 100-mg up-titration. Overall, 97% of up-titrated patients achieved target urate levels with median final allopurinol dose of 300 mg daily. Side effects and complications of up-titration were minimal. Overall, 36% of FAST patients were not at target urate levels and required up-titration. Allopurinol up-titration was effective in achieving urate target levels and was generally well tolerated by patients. Copyright © 2014 Elsevier Inc. All rights reserved.

The predictive value of drug-induced sleep endoscopy for CPAP titration in OSA patients.

PubMed

Lan, Ming-Chin; Hsu, Yen-Bin; Lan, Ming-Ying; Huang, Yun-Chen; Kao, Ming-Chang; Huang, Tung-Tsun; Chiu, Tsan-Jen; Yang, Mei-Chen

2017-12-15

The aim of this study was to identify possible upper airway obstructions causing a higher continuous positive airway pressure (CPAP) titration level, utilizing drug-induced sleep endoscopy (DISE). A total of 76 patients with obstructive sleep apnea (OSA) underwent CPAP titration and DISE. DISE findings were recorded using the VOTE classification system. Polysomnographic (PSG) data, anthropometric variables, and patterns of airway collapse during DISE were analyzed with CPAP titration levels. A significant association was found between the CPAP titration level and BMI, oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and neck circumference (NC) (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively, by Spearman correlation). Patients with concentric collapse of the velum or lateral oropharyngeal collapse were associated with a significantly higher CPAP titration level (P < 0.001 and P = 0.043, respectively, by nonparametric Mann-Whitney U test; P < 0.001 and P = 0.004, respectively, by Spearman correlation). No significant association was found between the CPAP titration level and any other collapse at the tongue base or epiglottis. By analyzing PSG data, anthropometric variables, and DISE results with CPAP titration levels, we can better understand possible mechanisms resulting in a higher CPAP titration level. We believe that the role of DISE can be expanded as a tool to identify the possible anatomical structures that may be corrected by oral appliance therapy or surgical intervention to improve CPAP compliance.

Economic benefit of back titration in the treatment of hypertension in Jos, Nigeria.

PubMed

Okeahialam, Basil N; Adeniyi, Michael A

2017-01-01

Treatment of hypertension is expensive and cost is one of the reasons for inadequate blood pressure control. Where there are no social cost cushions, the burden is borne by patients. With pervasive poverty and inadequate control, complications are unchecked. Back titration in appropriate circumstances should, therefore, translate to economic benefit. This is an attempt to compute, in economic terms, the benefit of back titration. Thirty-nine patients who entered an antihypertensive back titration program for 12 months and who had been earlier reported on, form the subject of this study. A survey of the cost of antihypertensives in pharmacy outlets in Jos, Nigeria was undertaken. Regimens of antihypertensives that patients were on at the onset and end of the 12 months of back titration were costed in Nigerian currency and compared. Back titration translated to economic benefit in all patients with a cost reduction varying from 2.3% to 100%. This reflected in reduction in mean daily cost of treatment of N107.09-N54.61. The benefit of antihypertensive back titration apart from psychological relief of lower pill burden and side effect profile is in pharmacoeconomics. This permits greater adherence and prevents morbi-mortality consequences of hypertension. In this study, back titration over 12 months translated to average cost reduction of >50%, making treatment more affordable. In appropriate circumstances, back titration of antihypertensives results in economic relief for patients. This should improve adherence, reduce morbi-mortality and is recommended for wider application.

Concentration determination of methyl magnesium chloride and other Grignard reagents by potentiometric titration with in-line characterization of reaction species by FTIR spectroscopy.

PubMed

Chen, Yadan; Wang, Tao; Helmy, Roy; Zhou, George X; LoBrutto, Rosario

2002-07-01

A potentiometric titration method for methyl magnesium chloride and other Grignard reagents based on the reaction with 2-butanol in THF has been developed and validated. The method employs a commercially available platinum electrode, using an electrolyte compatible with non-aqueous solvents. Well-defined titration curves were obtained, along with excellent method precision. The endpoint was precisely determined based on the first derivative of the titration curve. Different solvents such as THF, diethyl ether and methylene chloride provided similar results with regard to sharpness of the endpoint and method precision. The method was applied to a wide array of Grignard reagents including methyl magnesium bromide, ethyl magnesium chloride, propyl magnesium chloride, vinyl magnesium chloride, phenyl magnesium chloride, and benzyl magnesium chloride with similar precision and accuracy. Application of in-line FTIR was demonstrated for in situ monitoring of the titration reaction, allowing characterization of the reaction species. An authentic spectrum of the MeMgCl-THF complex was obtained using spectral subtraction and the vibrational absorbance bands were identified. FTIR also provided an alternative for detecting the titration endpoint, and the titration results so obtained, provided a cross-validation of the accuracy of the potentiometric titration.

Determination of polyhexamethylene biguanide hydrochloride using photometric colloidal titration with crystal violet as a color indicator.

PubMed

Masadome, Takashi; Miyanishi, Takaaki; Watanabe, Keita; Ueda, Hiroshi; Hattori, Toshiaki

2011-01-01

A solution of polyhexamethylene biguanide hydrochloride (PHMB-HCl) was titrated with a standard solution of potassium poly(vinyl sulfate) (PVSK) using crystal violet (CV) as an photometric indicator cation. The end point was detected by a sharp absorbance change due to an abrupt decrease in the concentration of CV. A linear relationship between the concentration of PHMB-HCl and the end-point volume of the titrant existed in the concentration range from 2 to 10 × 10(-6) eq mol L(-1). Back-titration was based on adding an excess amount of PVSK to a sample solution containing CV, which was titrated with a standard solution of poly(diallyldimethylammonium chloride) (PDADMAC). The calibration curve of the PHMB-HCl concentration to the end point volume of the titrant was also linear in the concentration range from 2 to 8 × 10(-6) eq mol L(-1). Both photometric titrations were applied to the determination of PHMB-HCl in a few contact-lens detergents. Back-titration showed a clear end point, but direct titration showed an unclear end point. The results of the back-titration of PHMB-HCl were compared with the content registered in its labels. 2011 © The Japan Society for Analytical Chemistry

Titration in the treatment of the more troubled patient.

PubMed

Winer, J A; Ornstein, E D

2001-01-01

This article defines and discusses a modification of technique recommended by the authors in the psychoanalytic treatment of more troubled patients--a modification they call titration. Titration is defined as a conscious decision by the analyst to increase or decrease assistance (or gratification) gradually, in order to facilitate the analytic process. The authors emphasize the complexity of decisions in treatment by focusing on the decision-making processes that titration requires. Guidelines and a case vignette are presented. The authors conclude by considering some of the politics involved in the introduction of technique modifications, the salience of the titration concept, and directions for further exploration.

The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization.

PubMed

Fong, Lam-Kiu; Wang, Ziwei; Schatz, George C; Luijten, Erik; Mirkin, Chad A

2018-05-23

DNA hybridization onto DNA-functionalized nanoparticle surfaces (e.g., in the form of a spherical nucleic acid (SNA)) is known to be enhanced relative to hybridization free in solution. Surprisingly, via isothermal titration calorimetry, we reveal that this enhancement is enthalpically, as opposed to entropically, dominated by ∼20 kcal/mol. Coarse-grained molecular dynamics simulations suggest that the observed enthalpic enhancement results from structurally confining the DNA on the nanoparticle surface and preventing it from adopting enthalpically unfavorable conformations like those observed in the solution case. The idea that structural confinement leads to the formation of energetically more stable duplexes is evaluated by decreasing the degree of confinement a duplex experiences on the nanoparticle surface. Both experiment and simulation confirm that when the surface-bound duplex is less confined, i.e., at lower DNA surface density or at greater distance from the nanoparticle surface, its enthalpy of formation approaches the less favorable enthalpy of duplex formation for the linear strand in solution. This work provides insight into one of the most important and enabling properties of SNAs and will inform the design of materials that rely on the thermodynamics of hybridization onto DNA-functionalized surfaces, including diagnostic probes and therapeutic agents.

Process monitored spectrophotometric titration coupled with chemometrics for simultaneous determination of mixtures of weak acids.

PubMed

Liao, Lifu; Yang, Jing; Yuan, Jintao

2007-05-15

A new spectrophotometric titration method coupled with chemometrics for the simultaneous determination of mixtures of weak acids has been developed. In this method, the titrant is a mixture of sodium hydroxide and an acid-base indicator, and the indicator is used to monitor the titration process. In a process of titration, both the added volume of titrant and the solution acidity at each titration point can be obtained simultaneously from an absorption spectrum by least square algorithm, and then the concentration of each component in the mixture can be obtained from the titration curves by principal component regression. The method only needs the information of absorbance spectra to obtain the analytical results, and is free of volumetric measurements. The analyses are independent of titration end point and do not need the accurate values of dissociation constants of the indicator and the acids. The method has been applied to the simultaneous determination of the mixtures of benzoic acid and salicylic acid, and the mixtures of phenol, o-chlorophenol and p-chlorophenol with satisfactory results.

Mevalonate 5-diphosphate mediates ATP binding to the mevalonate diphosphate decarboxylase from the bacterial pathogen Enterococcus faecalis

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

Chen, Chun-Liang; Mermoud, James C.; Paul, Lake N.

The mevalonate pathway produces isopentenyl diphosphate (IPP), a building block for polyisoprenoid synthesis, and is a crucial pathway for growth of the human bacterial pathogen Enterococcus faecalis. The final enzyme in this pathway, mevalonate diphosphate decarboxylase (MDD), acts on mevalonate diphosphate (MVAPP) to produce IPP while consuming ATP. This essential enzyme has been suggested as a therapeutic target for the treatment of drug-resistant bacterial infections. Here, we report functional and structural studies on the mevalonate diphosphate decarboxylase from E. faecalis (MDDEF). The MDDEF crystal structure in complex with ATP (MDDEF–ATP) revealed that the phosphate-binding loop (amino acids 97–105) is notmore » involved in ATP binding and that the phosphate tail of ATP in this structure is in an outward-facing position pointing away from the active site. This suggested that binding of MDDEF to MVAPP is necessary to guide ATP into a catalytically favorable position. Enzymology experiments show that the MDDEF performs a sequential ordered bi-substrate reaction with MVAPP as the first substrate, consistent with the isothermal titration calorimetry (ITC) experiments. On the basis of ITC results, we propose that this initial prerequisite binding of MVAPP enhances ATP binding. In summary, our findings reveal a substrate-induced substrate-binding event that occurs during the MDDEF-catalyzed reaction. The disengagement of the phosphate-binding loop concomitant with the alternative ATP-binding configuration may provide the structural basis for antimicrobial design against these pathogenic enterococci.« less

Aza-macrocyclic Triphenylamine Ligands for G-Quadruplex Recognition.

PubMed

García-España, Enrique Victor; Pont, Isabel; González-García, Jorge; Inclán, Mario; Reynolds, Matthew; Delgado-Pinar, Estefanía; Albelda, M Teresa; Vilar, Ramon

2018-05-16

A new series of triphenylamine-based ligands with one (TPA1PY), two (TPA2PY) or three pending aza-macrocycle(s) (TPA3PY) have been synthesised and studied by means of pH-metric titrations, UV/Vis spectroscopy and fluorescence experiments. The affinity of these ligands for G-quadruplex (G4) DNA and its selectivity over duplex DNA were investigated by FRET melting assays, fluorimetric titrations and circular dichroism (CD) spectroscopy. Interestingly, the interaction of the bi- and specially the tri-branched ligand with G4 leads to a very intense red-shifted fluorescence emission band which may be associated with intermolecular aggregation between the molecule and the DNA. This light-up effect allows the application of the ligands as fluorescence probes to selectivity detect G4. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determining association constants from titration experiments in supramolecular chemistry.

PubMed

Thordarson, Pall

2011-03-01

The most common approach for quantifying interactions in supramolecular chemistry is a titration of the guest to solution of the host, noting the changes in some physical property through NMR, UV-Vis, fluorescence or other techniques. Despite the apparent simplicity of this approach, there are several issues that need to be carefully addressed to ensure that the final results are reliable. This includes the use of non-linear rather than linear regression methods, careful choice of stoichiometric binding model, the choice of method (e.g., NMR vs. UV-Vis) and concentration of host, the application of advanced data analysis methods such as global analysis and finally the estimation of uncertainties and confidence intervals for the results obtained. This tutorial review will give a systematic overview of all these issues-highlighting some of the key messages herein with simulated data analysis examples.

An Olfactory Indicator for Acid-Base Titrations.

ERIC Educational Resources Information Center

Flair, Mark N.; Setzer, William N.

1990-01-01

The use of an olfactory acid-base indicator in titrations for visually impaired students is discussed. Potential olfactory indicators include eugenol, thymol, vanillin, and thiophenol. Titrations performed with each indicator with eugenol proved to be successful. (KR)

On-Board Monitoring of Engine Oil

DTIC Science & Technology

2011-04-01

Viscosity of Transparent and Opaque Liquids at 40°C Infracal Soot Meter Karl Fischer Titration ASTM D 664 Standard Test Method for Acid Number of... methods involve potentiometric and colorimetric titrations, respectively. For both tests, a titration solvent is prepared and added to the oil. The...ASTM D 2896 and ASTM D 4739 [17]. Both methods involve potentiometric titrations. ASTM D 2896 uses a stronger acid and more polar solvent than ASTM D

Efficacy and Tolerability of Two Different Kinds of Titration of Paroxetine Hydrocloride Solution: an Observational Study.

PubMed

Ielmini, Marta; Poloni, Nicola; Caselli, Ivano; Bianchi, Lucia; Diurni, Marcello; Vender, Simone; Callegari, Camilla

2018-03-13

Depressive disorders are expected to be the second highest cause of morbidity in the world until few years. Moreover, patients with depression frequently show many side effects and low compliance to therapy. To find a more tolerated and more efficacy therapy is a growing need. This observational study investigates the efficacy, safety and tolerability of paroxetine hydrochloride comparing slow versus standard titration in a population affected by Depressive Disoders (according to DSM 5). 186 outpatients were assessed throught the following scales: Hamilton Depression Rating Scale (HDRS) for depression and World Health Organization Quality of Life Scale Bref for the perceived quality of life (WHOQOL BREF). Treatment-emerged Adverse Events (TEAEs) were recorded throught self-reports. Statystical analysys was performed by GraphPad Prism Version 5.1. The efficacy of paroxetine was confirmed in both titrations by the number of clinical remitters (HDRS ≤ 7 at 12 weeks for 53% of the standard titration group and 58% of the slow titration group), without differences. About safety and tolerability there were more frequent TEAEs among the standard titration group (p < 0.01). Comparing WHOQOL BREF between the two groups at the recruitment and at the twelth week emerged a statistically significant difference (p = 0.003), with highest scores reached in slow titration group. Although the short observation period is an evident limit, this study is consistent to the literature about the efficacy of both titrations of paroxetine to improve depression and shows promising results about the increased tolerability of paroxetine slow titration.

Crystal structures of two novel dye-decolorizing peroxidases reveal a beta-barrel fold with a conserved heme-binding motif.

PubMed

Zubieta, Chloe; Krishna, S Sri; Kapoor, Mili; Kozbial, Piotr; McMullan, Daniel; Axelrod, Herbert L; Miller, Mitchell D; Abdubek, Polat; Ambing, Eileen; Astakhova, Tamara; Carlton, Dennis; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C; Duan, Lian; Elsliger, Marc-André; Feuerhelm, Julie; Grzechnik, Slawomir K; Hale, Joanna; Hampton, Eric; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K; Klock, Heath E; Knuth, Mark W; Kumar, Abhinav; Marciano, David; Morse, Andrew T; Nigoghossian, Edward; Okach, Linda; Oommachen, Silvya; Reyes, Ron; Rife, Christopher L; Schimmel, Paul; van den Bedem, Henry; Weekes, Dana; White, Aprilfawn; Xu, Qingping; Hodgson, Keith O; Wooley, John; Deacon, Ashley M; Godzik, Adam; Lesley, Scott A; Wilson, Ian A

2007-11-01

BtDyP from Bacteroides thetaiotaomicron (strain VPI-5482) and TyrA from Shewanella oneidensis are dye-decolorizing peroxidases (DyPs), members of a new family of heme-dependent peroxidases recently identified in fungi and bacteria. Here, we report the crystal structures of BtDyP and TyrA at 1.6 and 2.7 A, respectively. BtDyP assembles into a hexamer, while TyrA assembles into a dimer; the dimerization interface is conserved between the two proteins. Each monomer exhibits a two-domain, alpha+beta ferredoxin-like fold. A site for heme binding was identified computationally, and modeling of a heme into the proposed active site allowed for identification of residues likely to be functionally important. Structural and sequence comparisons with other DyPs demonstrate a conservation of putative heme-binding residues, including an absolutely conserved histidine. Isothermal titration calorimetry experiments confirm heme binding, but with a stoichiometry of 0.3:1 (heme:protein). (c) 2007 Wiley-Liss, Inc.

Selective Nitrate Recognition by a Halogen-Bonding Four-Station [3]Rotaxane Molecular Shuttle.

PubMed

Barendt, Timothy A; Docker, Andrew; Marques, Igor; Félix, Vítor; Beer, Paul D

2016-09-05

The synthesis of the first halogen bonding [3]rotaxane host system containing a bis-iodo triazolium-bis-naphthalene diimide four station axle component is reported. Proton NMR anion binding titration experiments revealed the halogen bonding rotaxane is selective for nitrate over the more basic acetate, hydrogen carbonate and dihydrogen phosphate oxoanions and chloride, and exhibits enhanced recognition of anions relative to a hydrogen bonding analogue. This elaborate interlocked anion receptor functions via a novel dynamic pincer mechanism where upon nitrate anion binding, both macrocycles shuttle from the naphthalene diimide stations at the periphery of the axle to the central halogen bonding iodo-triazolium station anion recognition sites to form a unique 1:1 stoichiometric nitrate anion-rotaxane sandwich complex. Molecular dynamics simulations carried out on the nitrate and chloride halogen bonding [3]rotaxane complexes corroborate the (1) H NMR anion binding results. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Manual and Flow-Injection Detection/Quantification of Polyquaterniums via Fully Reversible Polyion-Sensitive Polymeric Membrane-Based Ion-Selective Electrodes.

PubMed

Ferguson, Stephen A; Meyerhoff, Mark E

2017-10-27

The detection of four different polyquaterniums (PQs) using a fully reversible potentiometric polyion sensor in three different detection modes is described. The polyion sensing "pulstrodes" serve as the detector for direct dose-response experiments, beaker titrations, and in a flow-injection analysis (FIA) system. Direct polycation response toward PQ-2, PQ-6, PQ-10, and poly(2-methacryloxyethyltrimethylammonium) chloride (PMETAC) yields characteristic information about each PQ species (e.g., relative charge densities, etc.) via syringe pump addition of each PQ species to a background electrolyte solution. Quantitative titrations are performed using a syringe pump to deliver heparin as the polyanion titrant to quantify all four PQs at μg/mL levels. Both the direct and indirect methods incorporate the use of a three-electrode system including counter, double junction reference, and working electrodes. The working electrode possesses a plasticized poly(vinyl chloride) (PVC) membrane containing the neutral lipophilic salt of dinonylnaphthalenesulfonate (DNNS - ) tridodecylmethylammonium (TDMA + ). Further, the titration method is shown to be useful to quantify PQ-6 levels in recreational swimming pool water collected in Ann Arbor, MI. Finally, a FIA system equipped with a pulstrode detector is used to demonstrate the ability to potentially quantify PQ levels via a more streamlined and semiautomated testing platform.

A minimal titration model of the mammalian dynamical heat shock response

NASA Astrophysics Data System (ADS)

Sivéry, Aude; Courtade, Emmanuel; Thommen, Quentin

2016-12-01

Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response (HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms, having stress-induced activation and feedback regulations with multiple partners, the HSR is still incompletely understood. In this context, we propose a minimal molecular model for the gene regulatory network of the HSR that reproduces quantitatively different heat shock experiments both on heat shock factor 1 (HSF1) and HSPs activities. This model, which is based on chemical kinetics laws, is kept with a low dimensionality without altering the biological interpretation of the model dynamics. This simplistic model highlights the titration of HSF1 by chaperones as the guiding line of the network. Moreover, by a steady states analysis of the network, three different temperature stress regimes appear: normal, acute, and chronic, where normal stress corresponds to pseudo thermal adaption. The protein triage that governs the fate of damaged proteins or the different stress regimes are consequences of the titration mechanism. The simplicity of the present model is of interest in order to study detailed modelling of cross regulation between the HSR and other major genetic networks like the cell cycle or the circadian clock.

Preferential binding of daunomycin to 5'ATCG and 5'ATGC sequences revealed by footprinting titration experiments.

PubMed

Chaires, J B; Herrera, J E; Waring, M J

1990-07-03

Results from a high-resolution deoxyribonuclease I (DNase I) footprinting titration procedure are described that identify preferred daunomycin binding sites within the 160 bp tyr T DNA fragment. We have obtained single-bond resolution at 65 of the 160 potential binding sites within the tyr T fragment and have examined the effect of 0-3.0 microM total daunomycin concentration on the susceptibility of these sites toward digestion by DNase I. Four types of behavior are observed: (i) protection from DNase I cleavage; (ii) protection, but only after reaching a critical total daunomycin concentration; (iii) enhanced cleavage; (iv) no effect of added drug. Ten sites were identified as the most strongly protected on the basis of the magnitude of the reduction of their digestion product band areas in the presence of daunomycin. These were identified as the preferred daunomycin binding sites. Seven of these 10 sites are found at the end of the triplet sequences 5'ATGC and 5'ATCG, where the notation AT indicates that either A or T may occupy the position. The remaining three strongly protected sites are found at the ends of the triplet sequence 5'ATCAT. Of the preferred daunomycin binding sites we identify in this study, the sequence 5'ATCG is consistent with the specificity predicted by the theoretical studies of Chen et al. [Chen, K.-X., Gresh, N., & Pullman, B. (1985) J. Biomol. Struct. Dyn. 3, 445-466] and is the very sequence to which daunomycin is observed to be bound in two recent X-ray crystallographic studies. Solution studies, theoretical studies, and crystallographic studies have thus converged to provide a consistent and coherent picture of the sequence preference of this important anticancer antibiotic.

Identification of critical residues of subunit H in its interaction with subunit E of the A-ATP synthase from Methanocaldococcus jannaschii.

PubMed

Gayen, Shovanlal; Balakrishna, Asha M; Biuković, Goran; Yulei, Wu; Hunke, Cornelia; Grüber, Gerhard

2008-04-01

The boomerang-like H subunit of A(1)A(0) ATP synthase forms one of the peripheral stalks connecting the A(1) and A(0) sections. Structural analyses of the N-terminal part (H1-47) of subunit H of the A(1)A(0) ATP synthase from Methanocaldococcus jannaschii have been performed by NMR spectroscopy. Our initial NMR structural calculations for H1-47 indicate that amino acid residues 7-44 fold into a single alpha-helical structure. Using the purified N- (E1-100) and C-terminal domains (E101-206) of subunit E, NMR titration experiments revealed that the N-terminal residues Met1-6, Lys10, Glu11, Ala15, Val20 and Glu24 of H1-47 interact specifically with the N-terminal domain E1-100 of subunit E. A more detailed picture regarding the residues of E1-100 involved in this association was obtained by titration studies using the N-terminal peptides E1-20, E21-40 and E41-60. These data indicate that the N-terminal tail E41-60 interacts with the N-terminal amino acids of H1-47, and this has been confirmed by fluorescence correlation spectroscopy results. Analysis of (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra of the central stalk subunit F in the presence and absence of E101-206 show no obvious interaction between the C-terminal domain of E and subunit F. The data presented provide, for the first time, structural insights into the interaction of subunits E and H, and their arrangement within A(1)A(0) ATP synthase.

Single-stranded DNA Binding by the Helix-Hairpin-Helix Domain of XPF Protein Contributes to the Substrate Specificity of the ERCC1-XPF Protein Complex*

PubMed Central

Das, Devashish; Faridounnia, Maryam; Kovacic, Lidija; Kaptein, Robert; Boelens, Rolf; Folkers, Gert E.

2017-01-01

The nucleotide excision repair protein complex ERCC1-XPF is required for incision of DNA upstream of DNA damage. Functional studies have provided insights into the binding of ERCC1-XPF to various DNA substrates. However, because no structure for the ERCC1-XPF-DNA complex has been determined, the mechanism of substrate recognition remains elusive. Here we biochemically characterize the substrate preferences of the helix-hairpin-helix (HhH) domains of XPF and ERCC-XPF and show that the binding to single-stranded DNA (ssDNA)/dsDNA junctions is dependent on joint binding to the DNA binding domain of ERCC1 and XPF. We reveal that the homodimeric XPF is able to bind various ssDNA sequences but with a clear preference for guanine-containing substrates. NMR titration experiments and in vitro DNA binding assays also show that, within the heterodimeric ERCC1-XPF complex, XPF specifically recognizes ssDNA. On the other hand, the HhH domain of ERCC1 preferentially binds dsDNA through the hairpin region. The two separate non-overlapping DNA binding domains in the ERCC1-XPF heterodimer jointly bind to an ssDNA/dsDNA substrate and, thereby, at least partially dictate the incision position during damage removal. Based on structural models, NMR titrations, DNA-binding studies, site-directed mutagenesis, charge distribution, and sequence conservation, we propose that the HhH domain of ERCC1 binds to dsDNA upstream of the damage, and XPF binds to the non-damaged strand within a repair bubble. PMID:28028171

Binding of Cu(II) ions to peptides studied by fluorescence spectroscopy and isothermal titration calorimetry.

PubMed

Makowska, Joanna; Żamojć, Krzysztof; Wyrzykowski, Dariusz; Uber, Dorota; Wierzbicka, Małgorzata; Wiczk, Wiesław; Chmurzyński, Lech

2016-01-15

Steady-state and time-resolved fluorescence quenching measurements supported by Isothermal Titration Calorimetry (ITC) were used to study the interactions of Cu(2+) with four peptides. Two of them were taken from the N-terminal part of the FBP28 protein (formin binding protein) WW domain: Tyr-Lys-Thr-Ala-Asp-Gly-Lys-Thr-Tyr-NH2 (D9) and its mutant Tyr-Lys-Thr-Ala-Asn-Gly-Lys-Thr-Tyr-NH2 (D9_M) as well as two mutated peptides from the B3 domain of the immunoglobulin binding protein G derived from Streptococcus: Asp-Val-Ala-Thr-Tyr-Thr-NH2 (J1) and Glu-Val-Ala-Thr-Tyr-Thr-NH2 (J2). The measurements were carried out at 298.15K in 20mM 2-(N-morpholino)ethanesulfonic acid (MES) buffer solution with a pH of 6. The fluorescence of all peptides was quenched by Cu(2+) ions. The stoichiometry, conditional stability constants and thermodynamic parameters for the interactions of the Cu(2+) ions with D9 and D9_M were determined from the calorimetric data. The values of the conditional stability constants were additionally determined from fluorescence quenching measurements and compared with those obtained from calorimetric studies. There was a good correlation between data obtained from the two techniques. On the other hand, the studies revealed that J1 and J2 do not exhibit an affinity towards metal ions. The obtained results prove that fluorescence quenching experiments may be successfully used in order to determine stability constants of complexes with fluorescent ligands. Finally, based on the obtained results, the coordinating properties of the peptides towards the Cu(2+) ions are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

All-Atom Continuous Constant pH Molecular Dynamics With Particle Mesh Ewald and Titratable Water.

PubMed

Huang, Yandong; Chen, Wei; Wallace, Jason A; Shen, Jana

2016-11-08

Development of a pH stat to properly control solution pH in biomolecular simulations has been a long-standing goal in the community. Toward this goal recent years have witnessed the emergence of the so-called constant pH molecular dynamics methods. However, the accuracy and generality of these methods have been hampered by the use of implicit-solvent models or truncation-based electrostatic schemes. Here we report the implementation of the particle mesh Ewald (PME) scheme into the all-atom continuous constant pH molecular dynamics (CpHMD) method, enabling CpHMD to be performed with a standard MD engine at a fractional added computational cost. We demonstrate the performance using pH replica-exchange CpHMD simulations with titratable water for a stringent test set of proteins, HP36, BBL, HEWL, and SNase. With the sampling time of 10 ns per replica, most pK a 's are converged, yielding the average absolute and root-mean-square deviations of 0.61 and 0.77, respectively, from experiment. Linear regression of the calculated vs experimental pK a shifts gives a correlation coefficient of 0.79, a slope of 1, and an intercept near 0. Analysis reveals inadequate sampling of structure relaxation accompanying a protonation-state switch as a major source of the remaining errors, which are reduced as simulation prolongs. These data suggest PME-based CpHMD can be used as a general tool for pH-controlled simulations of macromolecular systems in various environments, enabling atomic insights into pH-dependent phenomena involving not only soluble proteins but also transmembrane proteins, nucleic acids, surfactants, and polysaccharides.

Binding of Cu(II) ions to peptides studied by fluorescence spectroscopy and isothermal titration calorimetry

NASA Astrophysics Data System (ADS)

Makowska, Joanna; Żamojć, Krzysztof; Wyrzykowski, Dariusz; Uber, Dorota; Wierzbicka, Małgorzata; Wiczk, Wiesław; Chmurzyński, Lech

2016-01-01

Steady-state and time-resolved fluorescence quenching measurements supported by Isothermal Titration Calorimetry (ITC) were used to study the interactions of Cu2 + with four peptides. Two of them were taken from the N-terminal part of the FBP28 protein (formin binding protein) WW domain: Tyr-Lys-Thr-Ala-Asp-Gly-Lys-Thr-Tyr-NH2 (D9) and its mutant Tyr-Lys-Thr-Ala-Asn-Gly-Lys-Thr-Tyr-NH2 (D9_M) as well as two mutated peptides from the B3 domain of the immunoglobulin binding protein G derived from Streptococcus: Asp-Val-Ala-Thr-Tyr-Thr-NH2 (J1) and Glu-Val-Ala-Thr-Tyr-Thr-NH2 (J2). The measurements were carried out at 298.15 K in 20 mM 2-(N-morpholino)ethanesulfonic acid (MES) buffer solution with a pH of 6. The fluorescence of all peptides was quenched by Cu2 + ions. The stoichiometry, conditional stability constants and thermodynamic parameters for the interactions of the Cu2 + ions with D9 and D9_M were determined from the calorimetric data. The values of the conditional stability constants were additionally determined from fluorescence quenching measurements and compared with those obtained from calorimetric studies. There was a good correlation between data obtained from the two techniques. On the other hand, the studies revealed that J1 and J2 do not exhibit an affinity towards metal ions. The obtained results prove that fluorescence quenching experiments may be successfully used in order to determine stability constants of complexes with fluorescent ligands. Finally, based on the obtained results, the coordinating properties of the peptides towards the Cu2 + ions are discussed.

M[superscript 2+]•EDTA Binding Affinities: A Modern Experiment in Thermodynamics for the Physical Chemistry Laboratory

ERIC Educational Resources Information Center

O'Brien, Leah C.; Root, Hannah B.; Wei, Chin-Chuan; Jensen, Drake; Shabestary, Nahid; De Meo, Cristina; Eder, Douglas J.

2015-01-01

Isothermal titration calorimetry was used to experimentally determine thermodynamic values for the ethylenediaminetetraacetic acid (EDTA)(aq) + M[superscript 2+](aq) reactions (M[superscript 2+] = Ca[superscript 2+] and Mg[superscript 2+]). Students showed that for reactions in a N-(2-hydroxyethyl)piperazine-N"-ethanesulfonic acid (HEPES)…

Measuring Norfloxacin Binding to Trypsin Using a Fluorescence Quenching Assay in an Upper-Division, Integrated Laboratory Course

ERIC Educational Resources Information Center

Hicks, Katherine A.

2016-01-01

Fluorescence quenching assays are often used to measure dissociation constants that quantify the binding affinity between small molecules and proteins. In an upper-division undergraduate laboratory course, where students work on projects using a guided inquiry-based approach, a binding titration experiment at physiological pH is performed to…

Determination of Calcium in Dietary Supplements: Statistical Comparison of Methods in the Analytical Laboratory

ERIC Educational Resources Information Center

Garvey, Sarah L.; Shahmohammadi, Golbon; McLain, Derek R.; Dietz, Mark L.

2015-01-01

A laboratory experiment is described in which students compare two methods for the determination of the calcium content of commercial dietary supplement tablets. In a two-week sequence, the sample tablets are first analyzed via complexometric titration with ethylenediaminetetraacetic acid and then, following ion exchange of the calcium ion present…

Integrating Chemistry Laboratory Instrumentation into the Industrial Internet: Building, Programming, and Experimenting with an Automatic Titrator

ERIC Educational Resources Information Center

Famularo, Nicole; Kholod, Yana; Kosenkov, Dmytro

2016-01-01

This project is designed to improve physical chemistry and instrumental analysis laboratory courses for undergraduate students by employing as teaching tools novel technologies in electronics and data integration using the industrial Internet. The project carried out by upper-division undergraduates is described. Students are exposed to a complete…

Identification of Unknown Chloride Salts Using a Combination of Qualitative Analysis and Titration with Silver Nitrate: A General Chemistry Laboratory

ERIC Educational Resources Information Center

Maines, Laina L.; Bruch, Martha D.

2012-01-01

General chemistry students often have difficulty writing balanced equations and performing stoichiometry calculations for precipitation reactions, in part because of difficulty understanding the symbolic notation used to represent chemical reactions. We have developed a problem-based experiment to improve student learning of these concepts, and…

Titration Calorimetry Standards and the Precision of Isothermal Titration Calorimetry Data

PubMed Central

Baranauskienė, Lina; Petrikaitė, Vilma; Matulienė, Jurgita; Matulis, Daumantas

2009-01-01

Current Isothermal Titration Calorimetry (ITC) data in the literature have relatively high errors in the measured enthalpies of protein-ligand binding reactions. There is a need for universal validation standards for titration calorimeters. Several inorganic salt co-precipitation and buffer protonation reactions have been suggested as possible enthalpy standards. The performances of several commercial calorimeters, including the VP-ITC, ITC200, and Nano ITC-III, were validated using these suggested standard reactions. PMID:19582227

Benefit of slow titration of paroxetine to treat depression in the elderly.

PubMed

Olgiati, Paolo; Bajo, Emanuele; Serretti, Alessandro

2014-11-01

Paroxetine is commonly used to treat depression in the elderly; however, titration issues have been raised. Rapid titration may lead to increased anxiety and early dropout. The aim of this cost-utility analysis was to compare the potential benefit of standard (10 mg the first day) versus slow titration (2.5 mg gradually increased). Clinical analysis was based on a naturalistic trial integrated with a decision-analytic model representing second treatments for those who initially did not respond and for dropout cases. Treatment setting was a public outpatient center for mental disorders in Italy. Service use data were estimated from best practice guidelines, whereas costs (Euros; 2012) were retrieved from Italian official sources. Slow titration approach produced 0.031 more quality-adjusted life years (remission rate: 57% vs 44% in standard titration group) at an incremental cost of €5.53 (generic paroxetine) and €54.54 (brand paroxetine syrup). Incremental cost-effectiveness ratio (ICER) values were €159 and €1768, respectively, in favor of slow titration approach. Cost-effectiveness threshold, defined as ICER < 1 GDP per capita according to World Health Organization criteria, is about €25 000 in Italy. Our results are consistent with a superiority of slow titration of paroxetine in older depressed patients. However, these findings, in part based on simulated data, need to be replicated in clinical trials. Copyright © 2014 John Wiley & Sons, Ltd.

Behavioral Effects of Neurofeedback Compared to Stimulants and Physical Activity in Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial.

PubMed

Geladé, Katleen; Janssen, Tieme W P; Bink, Marleen; van Mourik, Rosa; Maras, Athanasios; Oosterlaan, Jaap

2016-10-01

The efficacy of neurofeedback as a treatment for attention-deficit/hyperactivity disorder (ADHD), and whether neurofeedback is a viable alternative for stimulant medication, is still an intensely debated subject. The current randomized controlled trial compared neurofeedback to (1) optimally titrated methylphenidate and (2) a semi-active control intervention, physical activity, to account for nonspecific effects. A multicenter 3-way parallel-group study with balanced randomization was conducted. Children with a DSM-IV-TR diagnosis of ADHD, aged 7-13 years, were randomly allocated to receive neurofeedback (n = 39), methylphenidate (n = 36), or physical activity (n = 37) over a period of 10-12 weeks. Neurofeedback comprised theta/beta training on the vertex (Cz). Physical activity consisted of moderate to vigorous intensity exercises. Neurofeedback and physical activity were balanced in terms of number (~30) and duration of sessions. A double-blind pseudorandomized placebo-controlled crossover titration procedure was used to determine an optimal dose in the methylphenidate intervention. Parent and teacher ratings on the Strengths and Difficulties Questionnaire (SDQ) and Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN) were used to assess intervention outcomes. Data collection took place between September 2010 and March 2014. Intention-to-treat analyses revealed an improvement in parent-reported behavior on the SDQ and the SWAN Hyperactivity/Impulsivity scale, irrespective of received intervention (ηp² = 0.21-0.22, P ≤ .001), whereas the SWAN Inattention scale revealed more improvement in children who received methylphenidate than neurofeedback and physical activity (ηp² = 0.13, P ≤ .001). Teachers reported a decrease of ADHD symptoms on all measures for methylphenidate, but not for neurofeedback or physical activity (range of ηp² = 0.14-0.29, P < .001). The current study found that optimally titrated methylphenidate is superior to neurofeedback and physical activity in decreasing ADHD symptoms in children with ADHD. ClinicalTrials.gov identifier: NCT01363544. © Copyright 2016 Physicians Postgraduate Press, Inc.

Control of OSA During Automatic Positive Airway Pressure Titration in a Clinical Case Series: Predictors and Accuracy of Device Download Data

PubMed Central

Huang, Hsin-Chia Carol; Hillman, David R.; McArdle, Nigel

2012-01-01

Study Objectives: To investigate the factors associated with physiologic control of obstructive sleep apnea (OSA) during automatic positive airway pressure (APAP) titration in a clinical series. To also assess the usefulness of apnea-hypopnea index (AHI) data downloaded from the APAP device (Dev AHI). Design: Retrospective review of a consecutive series of patients with OSA who underwent APAP titration (Autoset Spirit, ResMed, Bella Vista, New South Wales, Australia ) with simultaneous polysomnographic (PSG) monitoring in the sleep laboratory. Setting: Tertiary sleep clinic. Participants: There were 190 consecutive patients with OSA referred for APAP titration. Measurements and Results: There were 58% of patients who achieved optimal or good control of OSA (titration PSG AHI < 10, or at least 50% reduction in AHI if diagnostic AHI < 15/hr) during APAP titration. The independent predictors of titration PSG AHI were a history of cardiac disease and elevated central apnea and arousal indices during the diagnostic study. Although the median and interquartile range (IQR) AHI from the device (7.0, 3.9-11.6 events/hr) was only slightly less than the PSG AHI (7.8, 3.9-14.4 events/hr, P = 0.04) during titration, case-by-case agreement between the two measures was poor (chi-square < 0.001). Conclusion: In a clinical sample control of OSA during APAP titration is often poor, and close clinical follow-up is particularly needed in patients with a history of cardiac disease or with high arousal or central apnea indices on the diagnostic study. Device AHI does not reliably assess control during APAP titration, and PSG assessment may be required if clinical response to treatment is poor. The findings relate to the ResMed AutoSet device and may not apply to other devices. Citation: Huang HCC; Hillman DR; McArdle N. Control of OSA during automatic positive airway pressure titration in a clinical case series: predictors and accuracy of device download data. SLEEP 2012;35(9):1277–1283. PMID:22942506

Interplay of charge distribution and conformation in peptides: comparison of theory and experiment.

PubMed

Makowska, Joanna; Bagińska, Katarzyna; Kasprzykowski, F; Vila, Jorge A; Jagielska, Anna; Liwo, Adam; Chmurzyński, Lech; Scheraga, Harold A

2005-01-01

We assessed the correlation between charge distribution and conformation of flexible peptides by comparing the theoretically calculated potentiometric-titration curves of two model peptides, Ac-Lys5-NHMe (a model of poly-L-lysine) and Ac-Lys-Ala11-Lys-Gly2-Tyr-NH2 (P1) in water and methanol, with the experimental curves. The calculation procedure consisted of three steps: (i) global conformational search of the peptide under study using the electrostatically driven Monte Carlo (EDMC) method with the empirical conformational energy program for peptides (ECEPP)/3 force field plus the surface-hydration (SRFOPT) or the generalized Born surface area (GBSA) solvation model as well as a molecular dynamics method with the assisted model building and energy refinement (AMBER)99/GBSA force field; (ii) reevaluation of the energy in the pH range considered by using the modified Poisson-Boltzmann approach and taking into account all possible protonation microstates of each conformation, and (iii) calculation of the average degree of protonation of the peptide at a given pH value by Boltzmann averaging over conformations. For Ac-Lys5-NHMe, the computed titration curve agrees qualitatively with the experimental curve of poly-L-lysine in 95% methanol. The experimental titration curves of peptide P1 in water and methanol indicate a remarkable downshift of the first pK(a) value compared to the values for reference compounds (n-butylamine and phenol, respectively), suggesting the presence of a hydrogen bond between the tyrosine hydroxyl oxygen and the H(epsilon) proton of a protonated lysine side chain. The theoretical titration curves agree well with the experimental curves, if conformations with such hydrogen bonds constitute a significant part of the ensemble; otherwise, the theory predicts too small a downward pH shift. Copyright 2005 Wiley Periodicals, Inc

Behavioral pattern of physicochemical constituents of the postharvest mango (Mangifera indica L.) influenced by storage stimuli.

PubMed

Islam, Md Khairul

2013-12-15

An investigation was carried at the laboratory of the Department of Biochemistry and Molecular Biology, University of Rajshahi, Bangladesh during the period from May, 2010 to September, 2011 to study the behavioral pattern of some physicochemical constituents of the mango pulp. The experiment was comprised of two popular mango cultivars in Bangladesh (viz., Langra and Khirshapat) and six storage stimuli, namely control, paraffin coating, perforated polyethylene cover, unperforated polyethylene cover, hot water (55 +/- 1 degree C) and low temperature (4 +/- 1 degree C). The two factors experiment was assigned in randomized complete block design with tree replicates. The varieties had profound variation in terms of most of the characters studied in the laboratory condition. Initially the Langra significantly enriched a greater amount of vitamin C (151.23 mg/100 g) and titratable acidity (4.31%) and these were decreased gradually with the progress of storage period. The Khirshapat showed higher pulp pH (5.83); produced enormous amount of TSS (18.00%) and sugar (TS = 17.62%, RS = 6.51% and NRS = 11.06%) content at 12th day of storage. The pH, TSS, sugar (TS, RS and NRS) content of mango pulp was rapidly increased, whereas vitamin C and titratable acidity decreased drastically from the untreated mangoes. On the other hand, low temperature retarded the changes. The Langra using low temperature (4 +/- 1 degree C) exhibited lower diminishing tendency in vitamin C and titratable acidity and also using no treatment slightly increased TSS; enriched enormous amount of sugar (TS, RS and NRS). Therefore, low temperature (4 +/- 1 degree C) was found satisfactory for delay ripening and postharvest changes of mango in storage condition.

Amelogenin as a promoter of nucleation and crystal growth of apatite

NASA Astrophysics Data System (ADS)

Uskoković, Vuk; Li, Wu; Habelitz, Stefan

2011-02-01

Human dental enamel forms over a period of 2-4 years by substituting the enamel matrix, a protein gel mostly composed of a single protein, amelogenin with fibrous apatite nanocrystals. Self-assembly of amelogenin and the products of its selective proteolytic digestion are presumed to direct the growth of apatite fibers and their organization into bundles that eventually comprise the mature enamel, the hardest tissue in the mammalian body. This work aimed to establish the physicochemical and biochemical conditions for the growth of apatite crystals under the control of a recombinant amelogenin matrix (rH174) in combination with a programmable titration system. The growth of apatite substrates was initiated in the presence of self-assembling amelogenin particles. A series of constant titration rate experiments was performed that allowed for a gradual increase of the calcium and/or phosphate concentrations in the protein suspensions. We observed a significant amount of apatite crystals formed on the substrates following the titration of rH174 sols that comprised the initial supersaturation ratio equal to zero. The protein layers adsorbed onto the substrate apatite crystals were shown to act as promoters of nucleation and growth of calcium phosphates subsequently formed on the substrate surface. Nucleation lag time experiments have showed that rH174 tends to accelerate precipitation from metastable calcium phosphate solutions in proportion to its concentration. Despite their mainly hydrophobic nature, amelogenin nanospheres, the size and surface charge properties of which were analyzed using dynamic light scattering, acted as a nucleating agent for the crystallization of apatite. The biomimetic experimental setting applied in this study proves as convenient for gaining insight into the fundamental nature of the process of amelogenesis.

Photoaffinity Labeling Studies on a Promoter of Dendritic Spine Formation

NASA Astrophysics Data System (ADS)

Sibucao, Kevin Carlo Abril

The small molecule BTA-EG4 has been shown to be a promoter of dendritic spine formation. The mechanism behind this phenomenon, however, is not well understood. The work in this dissertation is motivated by this gap in knowledge. The first part of this dissertation focuses on photoaffinity labeling studies to identify the cellular targets of BTA-EG4. Chapter 1 provides a summary of Alzheimer's disease, the rational design of BTA-EG 4, and methods to determine targets of small molecules. In Chapter 2, the synthesis of a BTA-EG4-based photoaffinity labeling probe and photodegradation studies are presented. Kinetic studies demonstrate that the probe photolyzes rapidly under UV light. In Chapter 3, photoaffinity labeling studies and subsequent protein identification experiments are reported. Competition experiments with the photoaffinity labeling probe and BTA-EG4 demonstrate that the probe labels a 55-kDa protein specifically. Tandem mass spectrometry revealed that the 55-kDa protein is the actin binding protein fascin 1. The second part of this dissertation focuses on the major protein identified from photoaffinity labeling studies, fascin 1. Chapter 4 provides a brief survey of the structure and function of fascin 1. In Chapter 5, characterizations of the interaction between BTA-EG4 and fascin 1 are reported. Isothermal titration calorimetry confirms the physical binding between fascin 1 and BTA-EG6, a BTA-EG4 analog. Slow speed sedimentation assays reveal that BTA-EG4 does not affect the actin-bundling activity of fascin 1. However, GST pull-down experiments show that BTA-EG4 inhibits the binding of fascin 1 with the GTPase Rab35. In addition, this work demonstrates that BTA-EG4 may be mechanistically distinct from the known fascin inhibitor G2.

Initiation of Levodopa-Carbidopa Intestinal Gel Infusion Using Telemedicine (Video Communication System) Facilitates Efficient and Well-Accepted Home Titration in Patients with Advanced Parkinson’s Disease

PubMed Central

Willows, Thomas; Dizdar, Nil; Nyholm, Dag; Widner, Håkan; Grenholm, Peter; Schmiauke, Ursula; Urbom, Anna; Groth, Kristina; Larsson, Jörgen; Permert, Johan; Kjellander, Susanna

2017-01-01

Background: Levodopa-carbidopa intestinal gel (LCIG; Duodopa®) is used for continuous infusion in advanced Parkinson’s disease. To achieve optimal effect, the LCIG dose is individually titrated, traditionally conducted during hospitalization in Sweden. However, dose adjustment depends on surrounding conditions, physical activity, and emotional stress, which is why titration at home could be beneficial. Telemedicine (TM) using a video communication system offers alternative titration procedures, allowing LCIG initiation at home. Objective: Study objectives were to show the feasibility of TM for LCIG home titration, evaluate resource use, and assess patient, neurologist, and nurse satisfaction. Methods: Four clinics enrolled 15 patients to observe efficiency and feasibility of TM-based monitoring. Results: Patient median (range) age was 67 (52–73) years and time since diagnosis was 10 (7–23) years. Median time between LCIG initiation and end of TM-assisted titration was 2.8 (2.0–13.8) days. Median time required for home titration by neurologists, nurses, and patients was (hours:minutes) 1 : 14 (0 : 29–1 : 52), 5 : 49 (2 : 46–10 : 3), and 8 : 53 (4 : 11–14 : 11), respectively. Neurologists and nurses considered this to be less time than required for hospital titration. TM allowed patients 92% free time from start to end of titration. Technical problems associated with TM contacts were rare, mostly related to digital link, and quickly resolved. Patients, neurologists, and nurses were satisfied using TM. No serious adverse events were reported; there was one device complaint (tube occlusion). Conclusions: In this study, TM-assisted LCIG titration at home was resource-efficient, technically feasible, well-accepted and was deemed satisfactory by patients, neurologists, and nurses. PMID:28984615

[Determination of peracetic acid and hydrogen peroxide in a preparation].

PubMed

Bodiroga, Milanka; Ognjanović, Jasminka

2002-01-01

Iodometric and permanganometric titrations were used for determination of peracetic acid and hydrogen peroxide (H2O2) in the mixture. Two procedures were described and compared. Titrations could be done in only one vessel, in the same reaction mixture, when iodometric titration of peracetic acid was continued after the permanganometric titration of H2O2, (procedure A). Peracetic acid and H2O2, as oxidizing agents, reacted with potassium iodide in an acid medium, evolving iodine. This reaction was used for the quantitative iodometric determination of total peroxide in procedure B. H2O2 reacted with potassium permanganate in acid medium, but peracetic acid did not react under the same conditions. That made possible the selective permanganometric determination of H2O2 in the presence of peracetic acid. The procedure B was performed in two titration vessels (KV = 3.4% for peracetic acid, 0.6% for H2O2). The procedure A for iodometric determination of peracetic acid in one titration vessel after permanganometric titration of H2O2 was recommended (KV = 2.5% for peracetic acid, 0.45% for H2O2).

A model for oxygen conservation associated with titration during pediatric oxygen therapy.

PubMed

Wu, Grace; Wollen, Alec; Himley, Stephen; Austin, Glenn; Delarosa, Jaclyn; Izadnegahdar, Rasa; Ginsburg, Amy Sarah; Zehrung, Darin

2017-01-01

Continuous oxygen treatment is essential for managing children with hypoxemia, but access to oxygen in low-resource countries remains problematic. Given the high burden of pneumonia in these countries and the fact that flow can be gradually reduced as therapy progresses, oxygen conservation through routine titration warrants exploration. To determine the amount of oxygen saved via titration during oxygen therapy for children with hypoxemic pneumonia. Based on published clinical data, we developed a model of oxygen flow rates needed to manage hypoxemia, assuming recommended flow rate at start of therapy, and comparing total oxygen used with routine titration every 3 minutes or once every 24 hours versus no titration. Titration every 3 minutes or every 24 hours provided oxygen savings estimated at 11.7% ± 5.1% and 8.1% ± 5.1% (average ± standard error of the mean, n = 3), respectively. For every 100 patients, 44 or 30 kiloliters would be saved-equivalent to 733 or 500 hours at 1 liter per minute. Ongoing titration can conserve oxygen, even performed once-daily. While clinical validation is necessary, these findings could provide incentive for the routine use of pulse oximeters for patient management, as well as further development of automated systems.

Home blood pressure monitoring and self-titration of antihypertensive medications: Proposed patient selection criteria.

PubMed

Hill, James R

2016-05-01

Recent studies have demonstrated that home blood pressure monitoring (HBPM), coupled with self-titration of medications is a viable intervention to control hypertension. There are currently no established criteria to evaluate patients for inclusion in such a program. The purpose of this discussion is to propose criteria for determining if a patient is appropriate to participate in a program of HBPM and self-titration. Inclusion criteria for two self-titration trials were examined, and additional factors in clinical practice were identified and discussed. Additional selection criteria were proposed to support the decision to enroll a patient in an antihypertensive self-titration program. Inclusion criteria from self-titration trials provide a reasonable starting point for choosing appropriate patients in clinical practice, but additional research is necessary. Adaptation of these criteria and consideration of the identified factors can be used to develop decision support instruments. Such instruments should be evaluated for effectiveness and reliability prior to use in clinical practice. HBPM combined with self-titration is an effective patient-centered approach for hypertension management. Decision support instruments to determine appropriate patients are necessary for safe and effective use in clinical practice. ©2015 American Association of Nurse Practitioners.

Thermometric titrations of amines with nitrosyl perchlorate in acetonitrile solvent.

PubMed

Gündüz, T; Kiliç, E; Cakirer, O

1996-05-01

Thirteen aliphatic and four aromatic amines, namely diethylamine, triethylamine, n-propylamine, di-n-propylamine, tri-n-butylamine, isopropylamine, di-isopropylamine, n-butylamine, di-n-butylamine, tri-n-butylamine, isobutylamine, sec-butylamine, tert-butylamine, aniline, N,N-dimethylaniline, 2-nitroaniline and 4-nitroaniline were titrated thermometrically with nitrosyl perchlorate in acetonitrile solvent. All the aliphatic amines gave very well-shaped thermometric titration curves. The calculated recovery values of the amines were very good. In comparison, the aromatic amines, aniline and N,N-dimethylaniline gave rather well-shaped titration curves, but the recovery values were fairly low. 2-Nitro- and 4-nitro anilines gave no thermometric response at all. The heats of reaction of the amines with nitrosyl perchlorate are rather high. However, the average heat of reaction of the aromatic amines is approximately two-thirds that of the average heat of the aliphatic amines. To support this method all the amines were also titrated potentiometrically and very similar results to those obtained with the thermometric method are seen. The nitrosyl ion is a Lewis acid, strong enough to titrate quantitatively aliphatic amines in acetonitrile solvent, but not strong enough to titrate aromatic amines at the required level in the same solvent.

pH Static Titration: A Quasistatic Approach

ERIC Educational Resources Information Center

Michalowski, Tadeusz; Toporek, Marcin; Rymanowski, Maciej

2007-01-01

The pH-static titration is applicable to those systems where at least two types of reactions occur in comparable intensities. The commonalities in titrimetric procedure realized according to pH-static titration, irrespective of the kind of chemical processes occurring are discussed.

The Potentiometric Titration of Filtrates from the Bachmann Process

DTIC Science & Technology

1942-06-23

SCIENTIFIC RESEARCH AND DEVELOP11ENT The Potentiometric Titration of Filtrates from the Bachmann Process (OD-12) by F. C. Whitmore OSRD No. 654... Potentiometric Titration of Synthetic Mixtures. A? Nitric Acid-Acetic Acid. A sample of 60 ml. glacial acetic acid war diluted to 200 ml. with distilled...i4flinflr?fj3 TADLE 1 CO) |S?lDBnTl» POTENTIOMETRIC TITRATION OF SYNTHETIC t’.IXTURES WITH CONCENTRATED AJKDNIUM HYDROXIDE A; unonium HNO-j- AcOfi Ky

Quantitative Determination of NTA and Other Chelating Agents in Detergents by Potentiometric Titration with Copper Ion Selective Electrode.

PubMed

Ito, Sana; Morita, Masaki

2016-01-01

Quantitative analysis of nitrilotriacetate (NTA) in detergents by titration with Cu 2+ solution using a copper ion selective electrode was achieved. This method tolerates a wide range of pH and ingredients in detergents. In addition to NTA, other chelating agents, having relatively lower stability constants toward Cu 2+ , were also qualified with sufficient accuracy by this analytical method for model detergent formulations. The titration process was automated by automatic titrating systems available commercially.

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

Pauli, Adam T; Robertson, Raymond E; Branthaver, Jan F

A system for determining parameters and compatibility of a substance such as an asphalt or other petroleum substance uses titration to highly accurately determine one or more flocculation occurrences and is especially applicable to the determination or use of Heithaus parameters and optimal mixing of various asphalt stocks. In a preferred embodiment, automated titration in an oxygen gas exclusive system and further using spectrophotometric analysis (2-8) of solution turbidity is presented. A reversible titration technique enabling in-situ titration measurement of various solution concentrations is also presented.

Process for Assessing the Stability of HAN (Hydroxylamine)-Based Liquid Propellants.

DTIC Science & Technology

1987-07-29

liquid propellants on the basis of HAN according to Fig. 1 can be determined directly by Fischer titration. This method requires a special unit, as the...Wasserreagenzien nach Eugen Scholz fUr die Karl - Fischer -Titration (Guidelines by Messrs. Riedel-de Haen for Titration according to the Karl Fischer ...Propellant components 2 2.2 Methods of determination 3 2.3 Acid/base titration and pK values 4 2.4 The Titroprozessor 636 8 2.5 Propellant analyses 10

Adherence to CPAP in patients with obstructive sleep apnea in a Chinese population.

PubMed

Wang, Yan; Gao, Weijie; Sun, Mei; Chen, Baoyuan

2012-02-01

CPAP is the first choice for most patients with obstructive sleep apnea (OSA), but the adherence to CPAP is suboptimal. The purpose of this study was to assess the adherence to CPAP therapy of Chinese OSA patients with CPAP therapy. Two-hundred ten patients who had been diagnosed with OSA and had experienced CPAP titration trial as prescribed were enrolled in this study. Subjects were identified by reviewing our Snoring and Sleep Apnea Unit's records. The patients were interviewed by telephone and were asked to assess their CPAP use time. Those who said their CPAP use time was less than 4 h/d for 70% of the nights per week were questioned about their reasons for non-adherence. Seventeen patients were lost to follow-up. One-hundred ninety-three patients participated in our survey. Patient demographics included male/female (162/31), mean ± SD age (51.91 ± 10.10 y), and mean apnea-hypopnea index (59.99 ± 21.51 events/h). At the time of the interview (59 ± 32 months after initial titration trial), 100 of 193 patients (51.8%) were still using CPAP, 29 of 193 patients (15.0%) had abandoned CPAP after using it for a period, and 64 of 193 patients (33.2%) had never commenced therapy after titration. The most common reasons cited by the patients for the poor adherence were they were not able to acclimatize to the CPAP during the titration night, they did not perceive the need or the benefits of the treatment, or found it troublesome to use CPAP every night. The CPAP adherence is low in Tianjin, China. Only one half of these patients remained adherent to the treatment, and the other one half of these patients either never initiated the treatment or had abandoned CPAP use. To improve CPAP adherence, the medical staff should pay attention to making the titration trial a comfortable first CPAP experience for the patients. It is also very important to give the patients education and support about CPAP use in the follow-up, especially early on in this treatment.

Value of routine investigations to predict loop diuretic down-titration success in stable heart failure.

PubMed

Martens, Pieter; Verbrugge, Frederik H; Boonen, Levinia; Nijst, Petra; Dupont, Matthias; Mullens, Wilfried

2018-01-01

Guidelines advocate down-titration of loop diuretics in chronic heart failure (CHF) when patients have no signs of volume overload. Limited data are available on the expected success rate of this practice or how routine diagnostic tests might help steering this process. Fifty ambulatory CHF-patients on stable neurohumoral blocker/diuretic therapy for at least 3months without any clinical sign of volume overload were prospectively included to undergo loop diuretic down-titration. All patients underwent a similar pre-down-titration evaluation consisting of a dyspnea scoring, physical examination, transthoracic echocardiography (diastolic function, right ventricular function, cardiac filling pressures and valvular disease), blood sample (serum creatinine, plasma NT-pro-BNP and neurohormones). Loop diuretic maintenance dose was subsequently reduced by 50% or stopped if dose was ≤40mg furosemide equivalents. Successful down-titration was defined as a persistent dose reduction after 30days without weight increase >1.5kg or new-onset symptoms of worsening heart failure. At 30-day follow-up, down-titration was successful in 62% (n=31). In 12/19 patients exhibiting down-titration failure, this occurred within the first week. Physical examination, transthoracic echocardiography and laboratory analysis had limited predictive capability to detect patients with down-titration success/failure (positive likelihood-ratios below 1.5, or area under the curve [AUC] non-statically different from AUC=0.5). Loop diuretic down-titration is feasible in a majority of stable CHF patients in which the treating clinician felt continuation of loops was unnecessary to sustain euvolemia. Importantly, routine diagnostics which suggest euvolemia, have limited diagnostic impact on the post-test probability. Copyright © 2017 Elsevier B.V. All rights reserved.

Immediate effect of CPAP titration on perceived health related quality of life: a prospective observational study.

PubMed

Iacono Isidoro, Serena; Salvaggio, Adriana; Lo Bue, Anna; Romano, Salvatore; Marrone, Oreste; Insalaco, Giuseppe

2016-12-01

Perceived Health Related Quality of Life (HRQoL) is impaired in obstructive sleep apnea (OSA). This study examines changes in HRQoL aspects occurring immediately after CPAP titration. Furthermore, we analyzed variations in each gender and in patients undergoing home or laboratory-based CPAP titration pathways. Twohundredfive outpatients (151 M) (56.7 ± 10.3 years) were evaluated, before first visit and nocturnal diagnostic examination (T0), and the morning after CPAP titration (T1). Two self-reported HRQoL questionnaires were administered: Psychological General Well-Being Index (PGWBI), composed by six subscales, and 12-Item Short-Form Health Survey (SF-12), including Physical (PCS) and Mental Component Summaries (MCS). CPAP titration was performed using auto-adjusting CPAP units at patients' home or in the sleep laboratory. PGWBI scores at T1 improved compared to T0 (p < 0.0001). A similar improvement was observed in SF-12 MCS (p = 0.0011), but not in SF-12 PCS. Changes were independent from anthropometric parameters, OSA severity and excessive daytime sleepiness. Gender comparisons showed better HRQoL in males at both times. At T0, patients who received home or laboratory CPAP titration pathways did not show any differences in PGWBI and SF-12 scores. At T1, PGWBI and SF-12 MCS improved in both home and laboratory groups. This study gives evidence that first time CPAP application for titration can lead to a general increase in perceived well-being. Gender comparisons showed better perceived HRQoL with more subscales improvements in males after CPAP titration. The improvement was similar with both home and laboratory CPAP titration pathways.

Effects of positive end-expiratory pressure titration and recruitment maneuver on lung inflammation and hyperinflation in experimental acid aspiration-induced lung injury.

PubMed

Ambrosio, Aline M; Luo, Rubin; Fantoni, Denise T; Gutierres, Claudia; Lu, Qin; Gu, Wen-Jie; Otsuki, Denise A; Malbouisson, Luiz M S; Auler, Jose O C; Rouby, Jean-Jacques

2012-12-01

In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

Impact of hypoglycemic events and HbA1c level on sulfonylurea discontinuation and down-titration.

PubMed

Laires, Pedro A; Tang, Jackson; Fan, Chun Po Steve; Li, Zhiyi; Qiu, Ying; Iglay, Kristy

2017-04-01

A retrospective cohort study using GE Centricity electronic medical records assessed the association between post-index hypoglycemia and HbA1c with discontinuation and down-titration of sulfonylureas among patients with Type 2 diabetes mellitus. Adult patients with an index prescription for a sulfonylurea and ≥12 months' continuous records pre- and post-index were eligible. Sulfonylurea discontinuation and down-titration was assessed 1-year post-index. Discontinuation occurred if the date of a prescription was >90 days from the preceding prescription plus days of supply. Down-titration occurred when a subsequent prescription was lower than the index dose. Cox regression assessed the association between post-index hypoglycemia and HbA1c with time to sulfonylurea discontinuation and down-titration, as well as other factors. 28,371 participants were included in the study; 13,459 (47.4%) were discontinuers, 717 (2.5%) were down-titraters, and 14,195 (50.0%) were continuers. 0.6% of continuers experienced hypoglycemia 1-year post-index, compared with 3.1% of down-titraters and 0.8% of discontinuers (p < 0.0001). Patients with post-index hypoglycemia had a significantly higher rate of discontinuation (hazard ratio [HR] = 1.82, 95% CI: 1.47-2.23) and down-titration (HR = 4.25, 95% CI: 1.92-8.03). Patients with higher post-index HbA1c and use of 2 nd generation sulfonylureas had an increased rate of discontinuation (HR = 1.05, 95% CI: 1.04-1.06; HR = 1.19, 95% CI: 1.14-1.24, respectively). Approximately half of participants who initiated sulfonylureas discontinued or down-titrated therapy within one year. Both post-index hypoglycemia and higher HbA1c were significant risk factors for sulfonylurea treatment change.

Potentiometric and electrokinetic signatures of iron(II) interactions with (α,γ)-Fe2O3.

PubMed

Toczydłowska, Diana; Kędra-Królik, Karolina; Nejbert, Krzysztof; Preočanin, Tajana; Rosso, Kevin M; Zarzycki, Piotr

2015-10-21

The electrochemical signatures of Fe(II) interactions with iron(III) oxides are poorly understood, despite their importance in controlling the amount of mobilized iron. Here, we report the potentiometric titration of α,γ-Fe2O3 oxides exposed to Fe(II) ions. We monitored in situ surface and ζ potentials, the ratio of mobilized ferric to ferrous, and the periodically analyzed nanoparticle crystal structure using X-ray diffraction. Electrokinetic potential reveals weak but still noticeable specific sorption of Fe(II) to the oxide surface under acidic conditions, and pronounced adsorption under alkaline conditions that results in a surface potential reversal. By monitoring the aqueous iron(II/III) fraction, we found that the addition of Fe(II) ions produces platinum electrode response consistent with the iron solubility-activity curve. Although, XRD analysis showed no evidence of γ-Fe2O3 transformations along the titration pathway despite iron cycling between aqueous and solid reservoirs, the magnetite formation cannot be ruled out.

Thermodynamics of the interaction of sweeteners and lactisole with fullerenols as an artificial sweet taste receptor model.

PubMed

Chen, Zhong-Xiu; Wu, Wen; Zhang, Wei-Bin; Deng, Shao-Ping

2011-09-01

The thermodynamics of the mimetic interaction of lactisole and sweeteners with fullerenols as a synthetic sweet receptor model was elucidated by Isothermal Titration Calorimetry (ITC) technique. The presence of lactisole resulted in great differences in thermodynamics of the sweeteners binding with fullerenols in which lactisole led to much more entropy contribution to the free energy compared with the interaction of sweeteners with fullerenols. Two interaction equilibrium states were found in ITC titration profiles and competitive binding of lactisole and sweeteners with fullerenols was disclosed. Our results indicated that the larger value of the ratio of two equilibrium constant K1/K2, the more effectively lactisole inhibited the sweetness of the sweetener. The combined results of sensory evaluation and ITC thermodynamics revealed that introducing a synthetic receptor model to interact with the sweeteners and inhibitors helps to understand the inhibition mechanism and the thermodynamic basis for the initiation of sweetness inhibition. Copyright © 2011 Elsevier Ltd. All rights reserved.

Highly accurate nephelometric titrimetry.

PubMed

Zhan, Xiancheng; Li, Chengrong; Li, Zhiyi; Yang, Xiucen; Zhong, Shuguang; Yi, Tao

2004-02-01

A method that accurately indicates the end-point of precipitation reactions by the measurement of the relative intensity of the scattered light in the titrate is presented. A new nephelometric titrator with an internal nephelometric sensor has been devised. The work of the titrator including the sensor and change in the turbidity of the titrate and intensity of the scattered light are described. The accuracy of the nephelometric titrimetry is discussed theoretically. The titration of NaCl with AgNO(3) serves as a model. A relative error as well as deviation is within 0.2% under the experimental conditions. The applicability of the titrimetry in pharmaceutical analyses, for example, phenytoin sodium and procaine hydrochloride, is generally illustrated. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association

Microtitration of various anions with quaternary ammonium halides using solid-state electrodes

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

Selig, W.

1980-01-01

Many solid-state electrodes were found to respond as endpoint detectors in the potentiometric titration of large inorganic and organic anions with quaternary ammonium halides. The best response was obtained with the iodide and cyanide electrodes although practically any electrode can function as endpoint sensor. The titrants were hexadecylpyridinium chloride and hexadecyltrimethylammonium chloride; hexadecyltrimethylammonium bromide and Hyamine 1622 may also be used. Some inorganic anions thus titratable are perrhenate, persulfate, ferricyanide, hexafluorophosphate, and hexachloroplatinate. Examples of organic anions titratable are nitroform, tetraphenylborate, cyanotriphenylborate, picrate, long-chain sulfates and sulfonates, and some soaps. The reverse titration of quaternary ammonium halides vs dodecylsulfate ismore » also feasible. Some titrations are feasible in a partially nonaqueous medium.« less

Symmetry Properties of Potentiometric Titration Curves.

ERIC Educational Resources Information Center

Macca, Carlo; Bombi, G. Giorgio

1983-01-01

Demonstrates how the symmetry properties of titration curves can be efficiently and rigorously treated by means of a simple method, assisted by the use of logarithmic diagrams. Discusses the symmetry properties of several typical titration curves, comparing the graphical approach and an explicit mathematical treatment. (Author/JM)

A Tabular Approach to Titration Calculations

ERIC Educational Resources Information Center

Lim, Kieran F.

2012-01-01

Titrations are common laboratory exercises in high school and university chemistry courses, because they are easy, relatively inexpensive, and they illustrate a number of fundamental chemical principles. While students have little difficulty with calculations involving a single titration step, there is a significant leap in conceptual difficulty…

LIGHT TITRATIONS

PubMed Central

Field, John; Baas-Becking, Lourens G. M.

1926-01-01

1. The usefulness of the radiomicrometer in titration work has been pointed out. The authors suggest that light titration may also be used where a reaction mixture changes its absorption in the (near) infra-red. 2. The applicability of this method to the starch-iodine reaction has been demonstrated. PMID:19872266

A Closer Look at Acid-Base Olfactory Titrations

ERIC Educational Resources Information Center

Neppel, Kerry; Oliver-Hoyo, Maria T.; Queen, Connie; Reed, Nicole

2005-01-01

Olfactory titrations using raw onions and eugenol as acid-base indicators are reported. An in-depth investigation on olfactory titrations is presented to include requirements for potential olfactory indicators and protocols for using garlic, onions, and vanillin as acid-base olfactory indicators are tested.

Host-Guest Interaction of Cucurbit[8]uril with N-(3-Aminopropyl)cyclohexylamine: Cyclohexyl Encapsulation Triggered Ternary Complex.

PubMed

Xia, Yu; Wang, Chuan-Zeng; Tian, Mengkui; Tao, Zhu; Ni, Xin-Long; Prior, Timothy J; Redshaw, Carl

2018-01-15

The host-guest interaction of a series of cyclohexyl-appended guests with cucurbit[8]uril (Q[8]) was studied by ¹H NMR spectroscopy, isothermal titration calorimetry (ITC), and X-ray crystallography. The X-ray structure revealed that two cycloalkane moieties can be simultaneously encapsulated in the hydrophobic cavity of the Q[8] host to form a ternary complex for the first time.

Switching From Age-Based Stimulus Dosing to Dose Titration Protocols in Electroconvulsive Therapy: Empirical Evidence for Better Patient Outcomes With Lower Peak and Cumulative Energy Doses.

PubMed

O'Neill-Kerr, Alex; Yassin, Anhar; Rogers, Stephen; Cornish, Janie

2017-09-01

The aim of this study was to test the proposition that adoption of a dose titration protocol may be associated with better patient outcomes, at lower treatment dose, and with comparable cumulative dose to that in patients treated using an age-based stimulus dosing protocol. This was an analysis of data assembled from archived records and based on cohorts of patients treated respectively on an age-based stimulus dosing protocol and on a dose titration protocol in the National Health Service in England. We demonstrated a significantly better response in the patient cohort treated with dose titration than with age-based stimulus dosing. Peak doses were less and the total cumulative dose was less in the dose titration group than in the age-based stimulus dosing group. Our findings are consistent with superior outcomes in patients treated using a dose titration protocol when compared with age-based stimulus dosing in a similar cohort of patients.

Potentiometric titration and equivalent weight of humic acid

USGS Publications Warehouse

Pommer, A.M.; Breger, I.A.

1960-01-01

The "acid nature" of humic acid has been controversial for many years. Some investigators claim that humic acid is a true weak acid, while others feel that its behaviour during potentiometric titration can be accounted for by colloidal adsorption of hydrogen ions. The acid character of humic acid has been reinvestigated using newly-derived relationships for the titration of weak acids with strong base. Re-interpreting the potentiometric titration data published by Thiele and Kettner in 1953, it was found that Merck humic acid behaves as a weak polyelectrolytic acid having an equivalent weight of 150, a pKa of 6.8 to 7.0, and a titration exponent of about 4.8. Interdretation of similar data pertaining to the titration of phenol-formaldehyde and pyrogallol-formaldehyde resins, considered to be analogs for humic acid by Thiele and Kettner, leads to the conclusion that it is not possible to differentiate between adsorption and acid-base reaction for these substances. ?? 1960.

A systematic review on the effectiveness of titratable over nontitratable mandibular advancement appliances for sleep apnea.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2017-01-01

Mandibular advancement appliances are being tested for use in patients with obstructive sleep apnea (OSA). However, the effectiveness of titration of these appliances does not have conclusive evidence. Systematic reviews help us to compile all available clinical evidence using statistical principles. Hence, the aim of this systematic review is to identify the effectiveness of titratable over nontitratable mandibular advancement appliances in patients with mild to moderate OSA. This review objective is to identify if titration of these appliances produce significant benefits over fixed appliances. Electronic databases were searched to identify eligible studies based on set inclusion criteria. Data extraction form was created and the data were extracted. The participants were mild to moderate OSA patients who received mandibular advancement appliances. Studies included a comparison between titratable and nontitratable mandibular advancement appliance. Of the five included studies, three were observational and two were a randomized trial. All these studies were conducted in adults. The outcome attributes were polysomnographic readings and apnea-hypopnea index (AHI). A significant heterogeneity was seen between the eligible studies and hence a meta-analysis could not be performed. The results from this systematic review did not show significant advantages of titratable appliances, although titratable appliances performed better from individual studies as regards to reduction in AHI and polysomnography. The reason is the lack of sufficient clinical trials on the same. More high quality randomized controlled trials comparing titratable and fixed appliances have to be initiated to get to conclusive evidence.

Antiepileptic Drug Titration and Related Health Care Resource Use and Costs.

PubMed

Fishman, Jesse; Kalilani, Linda; Song, Yan; Swallow, Elyse; Wild, Imane

2018-02-27

Unexpected breakthrough seizures resulting from suboptimal antiepileptic drug (AED) dosing during the titration period, as well as adverse events resulting from rapid AED titration, may influence the titration schedule and significantly increase health care resource use (HRU) and health care costs. To assess the relationship between AEDs, HRU, and costs during AED titration and maintenance. Practicing neurologists were recruited from a nationwide panel to provide up to 3 patient records each for this retrospective medical chart review. Patients with epilepsy who were aged ≥ 18 years and had initiated an AED between January 1, 2014, and January 1, 2016, were followed for 6 months from AED initiation. Titration duration was the time from AED initiation to the beginning of treatment maintenance as determined by the physician. Outcomes were epilepsy-specific HRU (hospitalizations, emergency department visits, outpatient visits, physician referral, laboratory testing/diagnostic imaging, and phone calls) and related costs that occurred during the titration or maintenance treatment periods. Of 811 patients, 156, 128, 125, 120, 114, 107, and 61 initiated the following AEDs: levetiracetam, lamotrigine, lacosamide, valproate, topiramate, carbamazepine, and phenytoin, respectively. Most patients (619/803 [77.1%] with complete AED data) received monotherapy. Baseline characteristics were similar across AEDs (mean [SD] age, 36.6 [14.4] years; 59.0% male). Kaplan-Meier estimates of titration duration ranged from 3.3 weeks (phenytoin) to 8.1 weeks (lamotrigine). From titration to maintenance, the overall incidence of HRU per person-month decreased 54.5%-89.3% for each HRU measure except outpatient visits (24.6% decrease). Total epilepsy-related costs decreased from $80.48 to $42.77 per person-month, or 46.9% from titration to maintenance. AED titration periods had higher HRU rates and costs than AED maintenance, suggesting that use of AEDs with shorter titration requirements reduces health care costs, although disease severity may also factor into overall cost. UCB Pharma sponsored this study and reviewed the manuscript. Fishman and Kalilani are employees of UCB Pharma. Wild was an employee of UCB Pharma at the time this analysis was conducted. Song and Swallow are employees of Analysis Group, which received funding from UCB Pharma. Study concept and design were contributed by Fishman, Kalilani, and Wild, along with other authors. Data collection was performed by Song and Swallow. All authors contributed to data interpretation. Writing of the manuscript was led by Fishman, Song, and Swallow, with revisions by all authors.

A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment.

PubMed

Ebben, Matthew R; Narizhnaya, Mariya; Segal, Alan Z; Barone, Daniel; Krieger, Ana C

2014-06-01

It has been found that mask style can affect the amount of continuous positive airway pressure (CPAP) required to reduce an apnoea/hyponoea index (AHI) to < 5/h on a titration study. However, it was not previously known whether switching from one CPAP mask style to another post titration could affect the residual AHI with CPAP. The purpose of this study was to investigate the differences in residual AHI with CPAP treatment between oronasal and nasal masks. Twenty-one subjects (age mean (M)=62.9, body mass index (BMI) M=29.6 kg/m2) were randomised (14 subjects completed the protocol) to undergo an in-laboratory CPAP titration with either a nasal mask or an oronasal mask. Subjects were then assigned this mask for 3weeks of at-home CPAP use with the optimal treatment pressure determined on the laboratory study (CPAP M=8.4 cm of H2O). At the end of this 3-week period, data were collected from the CPAP machine and the subject was given the other mask to use with the same CPAP settings for the next 3weeks at home (if the nasal mask was given initially, the oronasal one was given later and vice versa). On completion of the second 3-week period, data on residual AHI were again collected and compared with the first 3-week period on CPAP. A Wilcoxon Signed-Rank Test (two-tailed) revealed that residual AHI with CPAP treatment was significantly higher with the oronasal compared with the nasal mask (z = -3.296, p<0.001). All 14 subjects had a higher residual AHI with the oronasal versus nasal mask, and 50% of the subjects had a residual AHI >10/h in the oronasal mask condition, even though all of these subjects were titrated to an AHI of < 5/h in the laboratory. A higher residual AHI was seen in all patients with the use of an oronasal mask compared with a nasal mask. Switching to an oronasal mask post titration results in an increase in residual AHI with CPAP treatment, and pressure adjustment may be warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of sensorial experiments and their implementation into undergraduate laboratories

NASA Astrophysics Data System (ADS)

Bromfield Lee, Deborah Christina

"Visualization" of chemical phenomena often has been limited in the teaching laboratories to the sense of sight. We have developed chemistry experiments that rely on senses other than eyesight to investigate chemical concepts, make quantitative determinations, and familiarize students with chemical techniques traditionally designed using only eyesight. Multi-sensory learning can benefit all students by actively engaging them in learning through stimulation or an alternative way of experiencing a concept or ideas. Perception of events or concepts usually depends on the information from the different sensory systems combined. The use of multi-sensory learning can take advantage of all the senses to reinforce learning as each sense builds toward a more complete experience of scientific data. Research has shown that multi-sensory representations of scientific phenomena is a valuable tool for enhancing understanding of chemistry as well as displacing misconceptions through experience. Multi-sensory experiences have also been shown to enrich memory performance. There are few experiments published which utilize multiple senses in the teaching laboratory. The sensorial experiments chosen were conceptually similar to experiments currently performed in undergraduate laboratories; however students collect different types of data using multi-sensory observations. The experiments themselves were developed by using chemicals that would provide different sensory changes or capitalizing on sensory observations that were typically overlooked or ignored and obtain similar and precise results as in traditional experiments. Minimizing hazards and using safe practices are especially essential in these experiments as students utilize senses traditionally not allowed to be used in the laboratories. These sensorial experiments utilize typical equipment found in the teaching laboratories as well as inexpensive chemicals in order to aid implementation. All experiments are rigorously tested for accuracy and all chemicals examined for safety prior to implementation. The pedagogical objectives were established of to provide the ability to develop and stimulate students' conceptual understanding. The educational assessments of these experiments are are fashioned using the framework chosen (Marzano and Kendall). All the experiments are designed as collaborative, inquiry-based experiments in aims of enhancing the students understanding of the subject and promote critical thinking skills. These experiments use an investigative approach rather than verification methods. Terminology and misconceptions of the experiment were evaluated to prevent misunderstanding or confusion during the experiment. Interventions to address these misconceptions and learning problems associated with the experiment were developed. We have developed the Learning Lab Report, LLR, as an alternative model for the traditional laboratory reports, with the goal of transforming the traditional reports into something more useful for both students and instructors. The educational strategies are employed to develop this format in order to promote students to think critically about the concepts and take an active involvement in learning. From the results of the LLR, all experiments were reviewed and re-written to address any learning problems. The sensorial experiments study several topics usually covered in the first 2 years of the chemistry curriculum (general and organic chemistry courses). The experiments implemented, organic qualitative analysis, esterification kinetics, Le Chatelier equilibrium, thermometric titrations and ASA kinetics, worked effectively as students were able to draw correct conclusions about the concepts from the data obtained. An olfactory titration using the smell of the rutabaga vegetable has been developed and thoroughly tested. The LLR was utilized with the equilibrium, titration and acetyl salicylic acid experiments. The details of the development, implementation of these sensorial experiments and the LLR and student results are discussed.

Quantitative Analysis in the General Chemistry Laboratory: Training Students to Analyze Individual Results in the Context of Collective Data

ERIC Educational Resources Information Center

Ling, Chris D.; Bridgeman, Adam J.

2011-01-01

Titration experiments are ideal for generating large data sets for use in quantitative-analysis activities that are meaningful and transparent to general chemistry students. We report the successful implementation of a sophisticated quantitative exercise in which the students identify a series of unknown acids by determining their molar masses…

A Didactic Experience of Statistical Analysis for the Determination of Glycine in a Nonaqueous Medium Using ANOVA and a Computer Program

ERIC Educational Resources Information Center

Santos-Delgado, M. J.; Larrea-Tarruella, L.

2004-01-01

The back-titration methods are compared statistically to establish glycine in a nonaqueous medium of acetic acid. Important variations in the mean values of glycine are observed due to the interaction effects between the analysis of variance (ANOVA) technique and a statistical study through a computer software.

Quantification of Nicotine in Commercial Brand Cigarettes: How Much Is Inhaled by the Smoker?

ERIC Educational Resources Information Center

Vieira, Carlos A.; de Paiva, Sabina A. A.; Funai, Milena N. S.; Bergamaschi, Mateus M.; Queiroz, Regina H. C.; Giglio, Jose R.

2010-01-01

The main objective of this experiment is to determine the amount of nicotine in commercial brand cigarettes by means of a nonaqueous acid-base titration. A simple glass device simulating a smoker is proposed, which allows the determination of the volatilized, filter retained, and inhaled portions. Students will readily see that the amount of…

Further insights into the metal ion binding abilities and the metalation pathway of a plant metallothionein from Musa acuminata

PubMed Central

Cabral, Augusto C. S.; Jakovleska, Jovana; Deb, Aniruddha; Penner-Hahn, James E.; Pecoraro, Vincent L.

2017-01-01

The superfamily of metallothioneins (MTs) combines a diverse group of metalloproteins, sharing the characteristics of rather low molecular weight and high cysteine content. The latter provides MTs with the capability to coordinate thiophilic metal ions, in particular those with a d10 electron configuration. The sub-family of plant MT3 proteins is only poorly characterized and there is a complete lack of three-dimensional structure information. Building upon our previous results on the Musa acuminata MT3 (musMT3) protein, the focus of the present work is to understand the metal cluster formation process, the role of the single histidine residue present in musMT3, and the metal ion binding affinity. We concentrate our efforts on the coordination of ZnII and CdII ions, using CoII as a spectroscopic probe for ZnII binding. The overall protein-fold is analysed with a combination of limited proteolytic digestion, mass spectrometry, and dynamic light scattering. Histidine coordination of metal ions is probed with extended X-ray absorption fine structure spectroscopy and CoII titration experiments. Initial experiments with isothermal titration calorimetry provide insights into the thermodynamics of metal ion binding. PMID:29218632

Automatic photometric titrations of calcium and magnesium in carbonate rocks

USGS Publications Warehouse

Shapiro, L.; Brannock, W.W.

1955-01-01

Rapid nonsubjective methods have been developed for the determination of calcium and magnesium in carbonate rocks. From a single solution of the sample, calcium is titrated directly, and magnesium is titrated after a rapid removal of R2O3 and precipitation of calcium as the tungstate. A concentrated and a dilute solution of disodium ethylenediamine tetraacetate are used as titrants. The concentrated solution is added almost to the end point, then the weak solution is added in an automatic titrator to determine the end point precisely.

Determination of organic bases in non-aqueous solvents by catalytic thermometric titration.

PubMed

Vajgand, V J; Kiss, T A; Gaál, F F; Zsigrai, I J

1968-07-01

Catalytic thermometric titrations have been developed for bases (brucine, diethylaniline, potassium acetate and triethylamine) in acetic acid by continuous and discontinuous addition of the standard solution and automatic temperature recording. The determination of weak bases, e.g., antipyrine, unsuccessful in acetic acid by catalytic thermometric titration, has been achieved by using nitromethane or acetic anhydride as solvent. Catalytic thermometric titrations were also performed by coulometric generation of hydrogen ions for the determination of micro amounts of weak bases in a mixture of acetic anhyride and acetic acid.

Linear Titration Curves of Acids and Bases.

PubMed

Joseph, N R

1959-05-29

The Henderson-Hasselbalch equation, by a simple transformation, becomes pH - pK = pA - pB, where pA and pB are the negative logarithms of acid and base concentrations. Sigmoid titration curves then reduce to straight lines; titration curves of polyelectrolytes, to families of straight lines. The method is applied to the titration of the dipeptide glycyl aminotricarballylic acid, with four titrable groups. Results are expressed as Cartesian and d'Ocagne nomograms. The latter is of a general form applicable to polyelectrolytes of any degree of complexity.

Titration effectiveness of two autoadjustable continuous positive airway pressure devices driven by different algorithms in patients with obstructive sleep apnoea.

PubMed

Damiani, Mario Francesco; Quaranta, Vitaliano Nicola; Tedeschi, Ersilia; Drigo, Riccardo; Ranieri, Teresa; Carratù, Pierluigi; Resta, Onofrio

2013-08-01

Nocturnal application of continuous positive airway pressure (CPAP) is the standard treatment for patients with obstructive sleep apnoea (OSA). Determination of the therapeutic pressure (CPAP titration) is usually performed by a technician in the sleep laboratory during attended polysomnography. One possible alternative to manual titration is automated titration. Indeed, during the last 15 years, devices have been developed that deliver autoadjustable CPAP (A-CPAP). The aim of the present study was to compare the titration effectiveness of two A-CPAP devices using different flow-based algorithms in patients with OSA. This is a randomized study; 79 subjects underwent two consecutive unattended home A-CPAP titration nights with two different devices (Autoset Resmed; Remstar Auto Respironics); during the third and the fourth night, patients underwent portable monitoring in the sleep laboratory during fixed CPAP at the A-CPAP recommended pressure. Bland Altman plots showed good agreement between the recommended median and maximal pressure levels obtained with the two devices. A significant improvement was observed in all the sleep parameters by both A-CPAP machines to a similar degree. It was observed that the two A-CPAP devices using different algorithms are equally effective in initial titration of CPAP. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Overall Survival Analysis From a Randomized Phase II Study of Axitinib With or Without Dose Titration in First-Line Metastatic Renal Cell Carcinoma.

PubMed

Rini, Brian I; Tomita, Yoshihiko; Melichar, Bohuslav; Ueda, Takeshi; Grünwald, Viktor; Fishman, Mayer N; Uemura, Hirotsugu; Oya, Mototsugu; Bair, Angel H; Andrews, Glen I; Rosbrook, Brad; Jonasch, Eric

2016-12-01

In a randomized phase II trial in metastatic renal cell carcinoma (mRCC), objective response rate was significantly higher with axitinib versus placebo titration (54% vs. 34%; 1-sided P = .019). Treatment-naive patients with mRCC (n = 213) received axitinib 5 mg twice per day (b.i.d.) for 4 weeks. Patients meeting dose titration criteria were randomized to receive axitinib 5 mg b.i.d. with axitinib or placebo titration (n = 56 each); 91 patients ineligible for randomization continued axitinib 5 mg b.i.d.; 10 discontinued before randomization. Median overall survival (95% confidence interval [CI]) was 42.7 months (24.7-not estimable) with axitinib titration versus 30.4 months (23.7-45.0) with placebo titration (stratified hazard ratio, 0.785; 95% CI, 0.485-1.272; 1-sided P = .162), and 41.6 months (95% CI, 33.0-not estimable) in nonrandomized patients. Safety data were consistent with previous reports. Median overall survival was numerically longer in patients with first-line mRCC who received axitinib versus placebo titration. No new safety signal was observed after long-term axitinib treatment in first-line mRCC. Copyright © 2016 Elsevier Inc. All rights reserved.

A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease.

PubMed

Nakamura, Yu; Strohmaier, Christine; Tamura, Kaoru; Kataoka, Naoko; Nakano, Masayuki; Oda, Shoichiro; Nishimura, Kazuma; Homma, Akira

2015-01-01

To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm(2) and titrated to 10 cm(2) after 4 weeks) is well tolerated in Japanese patients with Alzheimer's disease (AD) as compared to 3-step titration (initiated at 2.5 cm(2) and titrated by 2.5 cm(2) every 4 weeks to 10 cm(2)). A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was -3.6% (95% confidence interval: -17.0, 9.6), falling within the prespecified acceptance range. The tolerability of two different titration schemes was similar in Japanese patients with AD.

A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease

PubMed Central

Nakamura, Yu; Strohmaier, Christine; Tamura, Kaoru; Kataoka, Naoko; Nakano, Masayuki; Oda, Shoichiro; Nishimura, Kazuma; Homma, Akira

2015-01-01

Aim To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm2 and titrated to 10 cm2 after 4 weeks) is well tolerated in Japanese patients with Alzheimer's disease (AD) as compared to 3-step titration (initiated at 2.5 cm2 and titrated by 2.5 cm2 every 4 weeks to 10 cm2). Methods A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. Results Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was −3.6% (95% confidence interval: −17.0, 9.6), falling within the prespecified acceptance range. Conclusion The tolerability of two different titration schemes was similar in Japanese patients with AD. PMID:26557135

A model for oxygen conservation associated with titration during pediatric oxygen therapy

PubMed Central

Wu, Grace; Wollen, Alec; Himley, Stephen; Austin, Glenn; Delarosa, Jaclyn; Izadnegahdar, Rasa; Ginsburg, Amy Sarah; Zehrung, Darin

2017-01-01

Background Continuous oxygen treatment is essential for managing children with hypoxemia, but access to oxygen in low-resource countries remains problematic. Given the high burden of pneumonia in these countries and the fact that flow can be gradually reduced as therapy progresses, oxygen conservation through routine titration warrants exploration. Aim To determine the amount of oxygen saved via titration during oxygen therapy for children with hypoxemic pneumonia. Methods Based on published clinical data, we developed a model of oxygen flow rates needed to manage hypoxemia, assuming recommended flow rate at start of therapy, and comparing total oxygen used with routine titration every 3 minutes or once every 24 hours versus no titration. Results Titration every 3 minutes or every 24 hours provided oxygen savings estimated at 11.7% ± 5.1% and 8.1% ± 5.1% (average ± standard error of the mean, n = 3), respectively. For every 100 patients, 44 or 30 kiloliters would be saved—equivalent to 733 or 500 hours at 1 liter per minute. Conclusions Ongoing titration can conserve oxygen, even performed once-daily. While clinical validation is necessary, these findings could provide incentive for the routine use of pulse oximeters for patient management, as well as further development of automated systems. PMID:28234903

Characterization of the Group A Streptococcus Mga Virulence Regulator Reveals a Role for the C-terminal Region in Oligomerization and Transcriptional Activation

PubMed Central

Hondorp, Elise R.; Hou, Sherry C.; Hempstead, Andrew D.; Hause, Lara L.; Beckett, Dorothy M.; McIver, Kevin S.

2012-01-01

The Group A Streptococcus (GAS) is a strict human pathogen that causes a broad spectrum of illnesses. One of the key regulators of virulence in GAS is the transcriptional activator Mga, which coordinates the early stages of infection. Although the targets of Mga have been well characterized, basic biochemical analyses have been limited due to difficulties in obtaining purified protein. In this study, high-level purification of soluble Mga was achieved, enabling the first detailed characterization of the protein. Fluorescence titrations coupled with filter-binding assays indicate that Mga binds cognate DNA with nanomolar affinity. Gel filtration analyses, analytical ultracentrifugation, and co-immunoprecipitation experiments demonstrate that Mga forms oligomers in solution. Moreover, the ability of the protein to oligomerize in solution was found to correlate with transcriptional activation; DNA binding appears to be necessary but insufficient for full activity. Truncation analyses reveal that the uncharacterized C-terminal region of Mga, possessing similarity to phosphotransferase system EIIB proteins, plays a critical role in oligomerization and in vivo activity. Mga from a divergent serotype was found to behave similarly, suggesting that this study describes a general mechanism for Mga regulation of target virulence genes within GAS and provides insight into related regulators in other Gram-positive pathogens. PMID:22468267

Probing intracellular motor protein activity using an inducible cargo trafficking assay.

PubMed

Kapitein, Lukas C; Schlager, Max A; van der Zwan, Wouter A; Wulf, Phebe S; Keijzer, Nanda; Hoogenraad, Casper C

2010-10-06

Although purified cytoskeletal motor proteins have been studied extensively with the use of in vitro approaches, a generic approach to selectively probe actin and microtubule-based motor protein activity inside living cells is lacking. To examine specific motor activity inside living cells, we utilized the FKBP-rapalog-FRB heterodimerization system to develop an in vivo peroxisomal trafficking assay that allows inducible recruitment of exogenous and endogenous kinesin, dynein, and myosin motors to drive specific cargo transport. We demonstrate that cargo rapidly redistributes with distinct dynamics for each respective motor, and that combined (antagonistic) actions of more complex motor combinations can also be probed. Of importance, robust cargo redistribution is readily achieved by one type of motor protein and does not require the presence of opposite-polarity motors. Simultaneous live-cell imaging of microtubules and kinesin or dynein-propelled peroxisomes, combined with high-resolution particle tracking, revealed that peroxisomes frequently pause at microtubule intersections. Titration and washout experiments furthermore revealed that motor recruitment by rapalog-induced heterodimerization is dose-dependent but irreversible. Our assay directly demonstrates that robust cargo motility does not require the presence of opposite-polarity motors, and can therefore be used to characterize the motile properties of specific types of motor proteins. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Secondary Structures in a Freeze-Dried Lignite Humic Acid Fraction Caused by Hydrogen-Bonding of Acidic Protons with Aromatic Rings.

PubMed

Cao, Xiaoyan; Drosos, Marios; Leenheer, Jerry A; Mao, Jingdong

2016-02-16

A lignite humic acid (HA) was separated from inorganic and non-HA impurities (i.e., aluminosilicates, metals) and fractionated by a combination of dialysis and XAD-8 resin. Fractionation revealed a more homogeneous structure of lignite HA. New and more specific structural information on the main lignite HA fraction is obtained by solid-state nuclear magnetic resonance (NMR) spectroscopy. Quantitative (13)C multiple cross-polarization (multiCP) NMR indicated oxidized phenyl propane structures derived from lignin. MultiCP experiments, conducted on potassium HA salts titrated to pH 10 and pH 12, revealed shifts consistent with carboxylate and phenolate formation, but structural changes associated with enolate formation from aromatic beta keto acids were not detected. Two-dimensional (1)H-(13)C heteronuclear correlation (2D HETCOR) NMR indicated aryl-aliphatic ketones, aliphatic and aromatic carboxyl groups, phenol, and methoxy phenyl ethers. Acidic protons from carboxyl groups in both the lignite HA fraction and a synthetic HA-like polycondensate were found to be hydrogen-bonded with electron-rich aromatic rings. Our results coupled with published infrared spectra provide evidence for the preferential hydrogen bonding of acidic hydrogens with electron-rich aromatic rings rather than adjacent carbonyl groups. These hydrogen-bonding interactions likely result from stereochemical arrangements in primary structures and folding.

A semi-grand canonical Monte Carlo simulation model for ion binding to ionizable surfaces: proton binding of carboxylated latex particles as a case study.

PubMed

Madurga, Sergio; Rey-Castro, Carlos; Pastor, Isabel; Vilaseca, Eudald; David, Calin; Garcés, Josep Lluís; Puy, Jaume; Mas, Francesc

2011-11-14

In this paper, we present a computer simulation study of the ion binding process at an ionizable surface using a semi-grand canonical Monte Carlo method that models the surface as a discrete distribution of charged and neutral functional groups in equilibrium with explicit ions modelled in the context of the primitive model. The parameters of the simulation model were tuned and checked by comparison with experimental titrations of carboxylated latex particles in the presence of different ionic strengths of monovalent ions. The titration of these particles was analysed by calculating the degree of dissociation of the latex functional groups vs. pH curves at different background salt concentrations. As the charge of the titrated surface changes during the simulation, a procedure to keep the electroneutrality of the system is required. Here, two approaches are used with the choice depending on the ion selected to maintain electroneutrality: counterion or coion procedures. We compare and discuss the difference between the procedures. The simulations also provided a microscopic description of the electrostatic double layer (EDL) structure as a function of pH and ionic strength. The results allow us to quantify the effect of the size of the background salt ions and of the surface functional groups on the degree of dissociation. The non-homogeneous structure of the EDL was revealed by plotting the counterion density profiles around charged and neutral surface functional groups. © 2011 American Institute of Physics

Kinetic release of hydrogen peroxide from different whitening products.

PubMed

da Silva Marques, Duarte Nuno; Silveira, Joao Miguel; Marques, Joana Rita; Amaral, Joao Almeida; Guilherme, Nuno Marques; da Mata, António Duarte

2012-01-01

The objective of this in vitro study was to evaluate the kinetics of hydrogen peroxide (HP) release from five different bleaching products: VivaStyle® 10% fitted tray gel, VivaStyle® 30% in-office bleaching gel, VivaStyle® Paint-On Plus paint-on bleaching varnish, Opalescence PF® 10% carbamide peroxide gel and Trèswhite Supreme™ 10% HP gel. Each product was firstly titrated for its HP content by a described method. HP release kinetics was assessed by a modified spectrophotometric technique. One sample t test was performed to test for differences between the manufacturers' claimed HP concentrations and the titrated HP content in the whitening products. Analysis of variance plus Tamhane's post hoc tests and Pearson correlation analysis were used as appropriate. Values of P < 0.05 were taken as significant. Titrated HP revealed an increased content when compared to the manufacturer's specifications for all the products tested (P < 0.05), although only products from one manufacturer produced significantly higher results. All products presented a significant (P < 0.05) and sustained release of HP. However, the product with paint-on cellulose-based matrix resulted in significantly (P < 0.05) faster kinetics when compared to other products tested. These results are consistent with manufacturers' reduced recommended application times. The results of this study suggest that modifying the matrix composition may be a viable alternative to HP concentration increase, since this may result in faster release kinetics without exposure to high HP concentrations.

The N-terminal Region of the Ubiquitin Regulatory X (UBX) Domain-containing Protein 1 (UBXD1) Modulates Interdomain Communication within the Valosin-containing Protein p97*

PubMed Central

Trusch, Franziska; Matena, Anja; Vuk, Maja; Koerver, Lisa; Knævelsrud, Helene; Freemont, Paul S.; Meyer, Hemmo; Bayer, Peter

2015-01-01

Valosin-containing protein/p97 is an ATP-driven protein segregase that cooperates with distinct protein cofactors to control various aspects of cellular homeostasis. Mutations at the interface between the regulatory N-domain and the first of two ATPase domains (D1 and D2) deregulate the ATPase activity and cause a multisystem degenerative disorder, inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia/amyotrophic lateral sclerosis. Intriguingly, the mutations affect only a subset of p97-mediated pathways correlating with unbalanced cofactor interactions and most prominently compromised binding of the ubiquitin regulatory X domain-containing protein 1 (UBXD1) cofactor during endolysosomal sorting of caveolin-1. However, how the mutations impinge on the p97-cofactor interplay is unclear so far. In cell-based endosomal localization studies, we identified a critical role of the N-terminal region of UBXD1 (UBXD1-N). Biophysical studies using NMR and CD spectroscopy revealed that UBXD1-N can be classified as intrinsically disordered. NMR titration experiments confirmed a valosin-containing protein/p97 interaction motif and identified a second binding site at helices 1 and 2 of UBXD1-N as binding interfaces for p97. In reverse titration experiments, we identified two distant epitopes on the p97 N-domain that include disease-associated residues and an additional interaction between UBXD1-N and the D1D2 barrel of p97 that was confirmed by fluorescence anisotropy. Functionally, binding of UBXD1-N to p97 led to a reduction of ATPase activity and partial protection from proteolysis. These findings indicate that UBXD1-N intercalates into the p97-ND1 interface, thereby modulating interdomain communication of p97 domains and its activity with relevance for disease pathogenesis. We propose that the polyvalent binding mode characterized for UBXD1-N is a more general principle that defines a subset of p97 cofactors. PMID:26475856

Clozapine Titration for People in Early Psychosis: A Chart Review and Treatment Guideline.

PubMed

Ballon, Jacob S; Ashfaq, Hera; Noordsy, Douglas L

2018-06-01

The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis. We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine. People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis. We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This approach resulted in clinical response at remarkably low maintenance doses of clozapine among people within their first year of illness, but not in those with longer duration of symptoms. Slow titration also led to good tolerability and acceptance of clozapine treatment for some patients.

Oxygen titration after resuscitation from out-of-hospital cardiac arrest: A multi-centre, randomised controlled pilot study (the EXACT pilot trial).

PubMed

Bray, Janet E; Hein, Cindy; Smith, Karen; Stephenson, Michael; Grantham, Hugh; Finn, Judith; Stub, Dion; Cameron, Peter; Bernard, Stephen

2018-04-21

Recent studies suggest the administration of 100% oxygen to hyperoxic levels following return-of-spontaneous-circulation (ROSC) post-cardiac arrest may be harmful. However, the feasibility and safety of oxygen titration in the prehospital setting is unknown. We conducted a multi-centre, phase-2 study testing whether prehospital titration of oxygen results in an equivalent number of patients arriving at hospital with oxygen saturations SpO2 ≥ 94%. We enrolled unconscious adults with: sustained ROSC; initial shockable rhythm; an advanced airway; and an SpO2 ≥ 95%. Initially (Sept 2015-March 2016) patients were randomised 1:1 to either 2 L/minute (L/min) oxygen (titrated) or >10 L/min oxygen (control) via a bag-valve reservoir. However, one site experienced a high number of desaturations (SpO2 < 94%) in the titrated arm and this arm was changed (April 2016) to an initial reduction of oxygen to 4 L/min then, if tolerated, to 2 L/min, and the desaturation limit was decreased to <90%. We randomised 61 patients to titrated (n = 37: 2L/min = 20 and 2-4 L/min = 17) oxygen or control (n = 24). Patients allocated to titrated oxygen were more likely to desaturate compared to controls ((SpO2 < 94%: 43% vs. 4%, p = 0.001; SpO2 < 90%: 19% vs. 4%, p = 0.09). The majority of desaturations (81%) occurred at 2L/min. On arrival at hospital the majority of patients had a SpO2 ≥ 94% (titrated: 90% vs. control: 100%) and all patients had a SpO2 ≥ 90%. One patient (control) re-arrested. Survival to hospital discharge was similar. Oxygen titration post-ROSC is feasible in the prehospital environment, but incremental titration commencing at 4L/min oxygen flow may be needed to maintain an oxygen saturation >90% (NCT02499042). Copyright © 2018 Elsevier B.V. All rights reserved.

40 CFR Appendix A to Part 425 - Potassium Ferricyanide Titration Method

Code of Federal Regulations, 2010 CFR

2010-07-01

... Method A Appendix A to Part 425 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Appendix A to Part 425—Potassium Ferricyanide Titration Method Source The potassium ferricyanide titration method is based on method SLM 4/2 described in “Official Method of Analysis,” Society of Leather Trades...

40 CFR Appendix A to Part 425 - Potassium Ferricyanide Titration Method

Code of Federal Regulations, 2012 CFR

2012-07-01

... Method A Appendix A to Part 425 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED..., App. A Appendix A to Part 425—Potassium Ferricyanide Titration Method Source The potassium ferricyanide titration method is based on method SLM 4/2 described in “Official Method of Analysis,” Society of...

40 CFR Appendix A to Part 425 - Potassium Ferricyanide Titration Method

Code of Federal Regulations, 2011 CFR

2011-07-01

... Method A Appendix A to Part 425 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Appendix A to Part 425—Potassium Ferricyanide Titration Method Source The potassium ferricyanide titration method is based on method SLM 4/2 described in “Official Method of Analysis,” Society of Leather Trades...

Sustainable conversion of agro-wastes into useful adsorbents

NASA Astrophysics Data System (ADS)

Bello, Olugbenga Solomon; Owojuyigbe, Emmanuel Seun; Babatunde, Monsurat Abiodun; Folaranmi, Folasayo Eunice

2017-11-01

Preparation and characterization of raw and activated carbon derived from three different selected agricultural wastes: kola nut pod raw and activated (KNPR and KNPA), bean husk raw and activated (BHR and BHA) and coconut husk raw and activated (CHR and CHA) were investigated, respectively. Influences of carbonization and acid activation on the activated carbon were investigated using SEM, FTIR, EDX, pHpzc and Boehm titration techniques, respectively. Carbonization was done at 350 °C for 2 h followed by activation with 0.3 M H3PO4 (ortho-phosphoric acid). Results obtained from SEM, FTIR, and EDX revealed that, carbonization followed by acid activation had a significant influence on morphology and elemental composition of the samples. SEM showed well-developed pores on the surface of the precursors after acid treatment, FTIR spectra revealed reduction, broadening, disappearance or appearance of new peaks after acid activation. EDX results showed highest percentage of carbon by atom respectively in the order BHA > KNPA > CHA respectively. The pHpzc was found to be 5.32, 4.57 and 3.69 for KNPA, BHA and CHA, respectively. Boehm titration result compliments that of pHpzc, indicating that the surfaces of the prepared adsorbents are predominantly acidic. This study promotes a sustainable innovative use of agro-wastes in the production of cheap and readily available activated carbons, thereby ensuring more affordable water and effluent treatment adsorbents.

Risk factors associated with treatment discontinuation and down-titration in type 2 diabetes patients treated with sulfonylureas.

PubMed

Iglay, Kristy; Qiu, Ying; Steve Fan, Chun-Po; Li, Zhiyi; Tang, Jackson; Laires, Pedro

2016-09-01

Sulfonylurea therapy among patients with type 2 diabetes mellitus (T2DM) can be disrupted due to adverse events, including hypoglycemia. A retrospective study using the MarketScan claims database quantified the frequency of sulfonylurea discontinuation or down-titration and identified associated risk factors. Adult patients with an index sulfonylurea prescription between 2008 and 2012 and 1 year continuous enrollment pre- and post-index were included. Therapy changes assessed over 1 year post-index included discontinuation and down-titration. Discontinuation occurred if the date of a fill was >90 days from the end date of the preceding fill. Down-titration occurred when a fill had a lower equivalent dose than the fill on the index date. Kaplan-Meier methods estimated the probability of either discontinuation or down-titration over 12 months, and Cox regression models identified associated risk factors. A total of 104,082 sulfonylurea users were included in the study and the probability of either discontinuation or down-titration at 3, 6 and 12 months was 23.2%, 38.9%, and 52.3%, respectively. Major risk factors associated with therapy changes included post-index hypoglycemia (discontinuation hazard ratio [HR] = 1.78 [1.68, 1.89]; down-titration HR =2.79 [2.40, 3.23]) and concomitant use of insulin (discontinuation HR =1.48 [1.40, 1.57]; down-titration HR =1.82 [1.56, 2.11]). Other risk factors included younger age, female gender, use of second generation sulfonylureas, prior cardiovascular comorbidity and liver disease. The study was not able to assess unreported, potentially mild cases of hypoglycemia, nor was it able to evaluate the association between changes in therapy and HbA1c levels or body weight. More than half of T2DM patients who initiated sulfonylurea therapy discontinued or down-titrated within 1 year. Insulin use and hypoglycemia were associated with sulfonylurea therapy change.

Dose Titration of Pregabalin in Patients with Painful Diabetic Peripheral Neuropathy: Simulation Based on Observational Study Patients Enriched with Data from Randomized Studies.

PubMed

Alexander, Joe; Edwards, Roger A; Manca, Luigi; Grugni, Roberto; Bonfanti, Gianluca; Emir, Birol; Whalen, Edward; Watt, Stephen; Parsons, Bruce

2018-03-01

Achieving a therapeutic response to pregabalin in patients with painful diabetic peripheral neuropathy (pDPN) requires adequate upward dose titration. Our goal was to identify relationships between titration and response to pregabalin in patients with pDPN. Data were integrated from nine randomized, placebo-controlled clinical trials as well as one 6-week open-label observational study conducted by 5808 physicians (2642 patients with pDPN) in standard outpatient settings in Germany. These studies evaluated pregabalin for treatment of pDPN. Using these data, we examined "what if" scenarios using a microsimulation platform that integrates data from randomized and observational sources as well as autoregressive-moving-average with exogenous inputs models that predict pain outcomes, taking into account weekly changes in pain, sleep interference, dose, and other patient characteristics that were unchanging. Final pain levels were significantly different depending on dose changes (P < 0.0001), with greater proportions improving with upward titration regardless of baseline pain severity. Altogether, 78.5% of patients with pDPN had 0-1 dose change, and 15.2% had ≥ 2 dose changes. Simulation demonstrated that the 4.8% of inadequately titrated patients who did not improve/very much improve their pain levels would have benefited from ≥ 2 dose changes. Patient satisfaction with tolerability (range 90.3-96.2%) was similar, regardless of baseline pain severity, number of titrations, or extent of improvement, suggesting that tolerability did not influence treatment response patterns. Upward dose titration reduced pain in patients with pDPN who actually received it. Simulation also predicted pain reduction in an inadequately titrated nonresponder subgroup of patients had they actually received adequate titration. The decision not to uptitrate must have been driven by factors other than tolerability. Pfizer, Inc.

Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy.

PubMed

Baulac, M; Byrnes, W; Williams, P; Borghs, S; Webster, E; De Backer, M; Dedeken, P

2017-04-01

To assess prospectively the effectiveness of lacosamide (LCM) added to levetiracetam (LEV) after down-titration of a concomitant sodium channel blocker (SCB) among patients with focal epilepsy not adequately controlled on LEV and SCB. In this open-label trial, LCM was initiated at 100 mg/day and up-titrated to 200-600 mg/day over 9 weeks; SCB down-titration started when LCM dose reached 200 mg/day. Patients remained on stable LCM/LEV doses for 12 weeks' maintenance (21-week treatment period). The primary outcome was retention rate on LCM. Due to recruitment challenges, fewer than the planned 300 patients participated in the trial, resulting in the trial being underpowered. Overall, 120 patients (mean age 39.7 years) started and 93 completed the trial. The most frequently used SCBs were lamotrigine (39.2%), carbamazepine (30.8%) and oxcarbazepine (27.5%). Eighty-four patients adhered to protocol and discontinued their SCB after cross-titration, but there was insufficient evidence for 36 patients. Retention rate was 73.3% (88/120) for all patients and 83.3% (70/84) for those with evidence of SCB discontinuation. Seizure freedom for patients completing maintenance was 14.0% (13/93). Discontinuation due to adverse events (6.7%) and lack of efficacy (3.3%) occurred primarily during cross-titration. Most frequently reported adverse events during treatment were dizziness (23.3%), headache (15.0%) and fatigue (8.3%). In patients with uncontrolled seizures on LEV/SCB, the LCM/LEV combination appeared to be effective and well tolerated. A cross-titration schedule-flexible LCM up-titration, concomitant SCB down-titration and stable background LEV-could present a feasible and practical approach to initiating LCM while minimizing pharmacodynamic interactions with a SCB. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Microcalorimetric and potentiometric titration studies on the adsorption of copper by P. putida and B. thuringiensis and their composites with minerals.

PubMed

Fang, Linchuan; Cai, Peng; Li, Pengxiang; Wu, Huayong; Liang, Wei; Rong, Xingmin; Chen, Wenli; Huang, Qiaoyun

2010-09-15

In order to have a better understanding of the interactions of heavy metals with bacteria and minerals in soil and associated environments, isothermal titration calorimetry (ITC), potentiometric titration and equilibrium sorption experiments were conducted to investigate the adsorption behavior of Cu(II) by Bacillus thuringiensis, Pseudomonas putida and their composites with minerals. The interaction of montmorillonite with bacteria increased the reactive sites and resulted in greater adsorption for Cu(II) on their composites, while decreased adsorption sites and capacities for Cu(II) were observed on goethite-bacteria composites. A gram-positive bacterium B. thuringiensis played a more important role than a gram-negative bacterium P. putida in determining the properties of the bacteria-minerals interfaces. The enthalpy changes (DeltaH(ads)) from endothermic (6.14 kJ mol(-1)) to slightly exothermic (-0.78 kJ mol(-1)) suggested that Cu(II) is complexed with the anionic oxygen ligands on the surface of bacteria-mineral composites. Large entropies (32.96-58.89 J mol(-1) K(-1)) of Cu(II) adsorption onto bacteria-mineral composites demonstrated the formation of inner-sphere complexes in the presence of bacteria. The thermodynamic data implied that Cu(II) mainly bound to the carboxyl and phosphoryl groups as inner-sphere complexes on bacteria and mineral-bacteria composites. Copyright 2010 Elsevier B.V. All rights reserved.

The kinetic study of the inhibition of human cholinesterases by demeton-S-methyl shows that cholinesterase-based titration methods are not suitable for this organophosphate.

PubMed

Bazire, Alexandre; Gillon, Emilie; Lockridge, Oksana; Vallet, Virginie; Nachon, Florian

2011-04-01

The organophosphorus insecticide, demeton-S-methyl (DSM), is considered as a good surrogate of the highly toxic nerve agent VX for skin absorption studies due to similar physico-chemical properties and in vitro percutaneous penetration profile. But, when skin distribution was estimated by measuring inhibition of cholinesterase activity, the results were poorly reproducible. The various grades of commercial DSM solutions were suspected to be the origin of the discrepancies. This hypothesis was tested by measuring inhibition of human acetyl- and butyrylcholinesterase by two commercial DSM solutions. The inhibition rate was independent on the enzyme concentration confirming pseudo-first order conditions. But complete inhibition of butyrylcholinesterase activity was achieved only when the DSM concentration was at least 1500-fold higher than the enzyme concentration. Besides, complete inhibition of acetylcholinesterase was never achieved. Mass spectrometry analysis of the inhibited butyrylcholinesterase adducts identified monomethoxyphosphorylated-serine, the aged product of inhibition by DSM or a derivative with a modified leaving group. Neither spontaneous reactivation nor aging of the dimethoxyphosphorylated-serine could account for the inhibition kinetics observed, suggesting an overly complicated kinetic scheme not compatible with the requirement of a titration experiment. In conclusion, cholinesterase-based analytical methods should be avoided for DSM titration in skin penetration studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Side chain-side chain interactions of arginine with tyrosine and aspartic acid in Arg/Gly/Tyr-rich domains within plant glycine-rich RNA binding proteins.

PubMed

Kumaki, Yasuhiro; Nitta, Katsutoshi; Hikichi, Kunio; Matsumoto, Takeshi; Matsushima, Norio

2004-07-01

Plant glycine-rich RNA-binding proteins (GRRBPs) contain a glycine-rich region at the C-terminus whose structure is quite unknown. The C-terminal glycine-rich part is interposed with arginine and tyrosine (arginine/glycine/tyrosine (RGY)-rich domain). Comparative sequence analysis of forty-one GRRBPs revealed that the RGY-rich domain contains multiple repeats of Tyr-(Xaa)h-(Arg)k-(Xaa)l, where Xaa is mainly Gly, "k" is 1 or 2, and "h" and "l" range from 0 to 10. Two peptides, 1 (G1G2Y3G4G5G6R7R8D9G10) and 2 (G1G2R3R4D5G6G7Y8G9G10), corresponding to sections of the RGY-rich domain in Zea mays RAB15, were selected for CD and NMR experiments. The CD spectra indicate a unique, positive band near 228 nm in both peptides that has been ascribed to tyrosine residues in ordered structures. The pH titration by NMR revealed that a side chain-side chain interaction, presumably an H-Nepsilon...O=Cgamma hydrogen bonding interaction in the salt bridge, occurs between Arg (i) and Asp (i + 2). 1D GOESY experiments indicated the presence of NOE between the aromatic side chain proton and the arginine side chain proton in the two peptides suggesting strongly that the Arg (i) aromatic side chain interacts directly with the Tyr (i +/- 4 or i +/- 5) side chain.

Pulsating potentiometric titration technique for assay of dissolved oxygen in water at trace level.

PubMed

Sahoo, P; Ananthanarayanan, R; Malathi, N; Rajiniganth, M P; Murali, N; Swaminathan, P

2010-06-11

A simple but high performance potentiometric titration technique using pulsating sensors has been developed for assay of dissolved oxygen (DO) in water samples down to 10.0 microg L(-1) levels. The technique involves Winkler titration chemistry, commonly used for determination of dissolved oxygen in water at mg L(-1) levels, with modification in methodology for accurate detection of end point even at 10.0 microg L(-1) levels DO present in the sample. An indigenously built sampling cum pretreatment vessel has been deployed for collection and chemical fixing of dissolved oxygen in water samples from flowing water line without exposure to air. A potentiometric titration facility using pulsating sensors developed in-house is used to carry out titration. The power of the titration technique has been realised in estimation of very dilute solution of iodine equivalent to 10 microg L(-1) O(2). Finally, several water samples containing dissolved oxygen from mg L(-1) to microg L(-1) levels were successfully analysed with excellent reproducibility using this new technique. The precision in measurement of DO in water at 10 microg L(-1) O(2) level is 0.14 (n=5), RSD: 1.4%. Probably for the first time a potentiometric titration technique has been successfully deployed for assay of dissolved oxygen in water samples at 10 microg L(-1) levels. Copyright 2010 Elsevier B.V. All rights reserved.

Evaluation of the 5 and 8 pH point titration methods for monitoring anaerobic digesters treating solid waste.

PubMed

Vannecke, T P W; Lampens, D R A; Ekama, G A; Volcke, E I P

2015-01-01

Simple titration methods certainly deserve consideration for on-site routine monitoring of volatile fatty acid (VFA) concentration and alkalinity during anaerobic digestion (AD), because of their simplicity, speed and cost-effectiveness. In this study, the 5 and 8 pH point titration methods for measuring the VFA concentration and carbonate system alkalinity (H2CO3*-alkalinity) were assessed and compared. For this purpose, synthetic solutions with known H2CO3*-alkalinity and VFA concentration as well as samples from anaerobic digesters treating three different kind of solid wastes were analysed. The results of these two related titration methods were verified with photometric and high-pressure liquid chromatography measurements. It was shown that photometric measurements lead to overestimations of the VFA concentration in the case of coloured samples. In contrast, the 5 pH point titration method provides an accurate estimation of the VFA concentration, clearly corresponding with the true value. Concerning the H2CO3*-alkalinity, the most accurate and precise estimations, showing very similar results for repeated measurements, were obtained using the 8 pH point titration. Overall, it was concluded that the 5 pH point titration method is the preferred method for the practical monitoring of AD of solid wastes due to its robustness, cost efficiency and user-friendliness.

A Full Automatic Device for Sampling Small Solution Volumes in Photometric Titration Procedure Based on Multicommuted Flow System

PubMed Central

Borges, Sivanildo S.; Vieira, Gláucia P.; Reis, Boaventura F.

2007-01-01

In this work, an automatic device to deliver titrant solution into a titration chamber with the ability to determine the dispensed volume of solution, with good precision independent of both elapsed time and flow rate, is proposed. A glass tube maintained at the vertical position was employed as a container for the titrant solution. Electronic devices were coupled to the glass tube in order to control its filling with titrant solution, as well as the stepwise solution delivering into the titration chamber. The detection of the titration end point was performed employing a photometer designed using a green LED (λ=545 nm) and a phototransistor. The titration flow system comprised three-way solenoid valves, which were assembled to allow that the steps comprising the solution container loading and the titration run were carried out automatically. The device for the solution volume determination was designed employing an infrared LED (λ=930 nm) and a photodiode. When solution volume delivered from proposed device was within the range of 5 to 105 μl, a linear relationship (R = 0.999) between the delivered volumes and the generated potential difference was achieved. The usefulness of the proposed device was proved performing photometric titration of hydrochloric acid solution with a standardized sodium hydroxide solution and using phenolphthalein as an external indicator. The achieved results presented relative standard deviation of 1.5%. PMID:18317510

Effects of Acute and Chronic Cocaine Administration on Titrating-Delay Matching-to-Sample Performance

ERIC Educational Resources Information Center

Kangas, Brian D.; Branch, Marc N.

2012-01-01

The effects of cocaine were examined under a titrating-delay matching-to-sample procedure. In this procedure, the delay between sample stimulus offset and comparison stimuli onset adjusts as a function of the subject's performance. Specifically, matches increase the delay and mismatches decrease the delay. Titrated delay values served as the…

Microscale pH Titrations Using an Automatic Pipet.

ERIC Educational Resources Information Center

Flint, Edward B.; Kortz, Carrie L.; Taylor, Max A.

2002-01-01

Presents a microscale pH titration technique that utilizes an automatic pipet. A small aliquot (1-5 mL) of the analyte solution is titrated with repeated additions of titrant, and the pH is determined after each delivery. The equivalence point is determined graphically by either the second derivative method or a Gran plot. The pipet can be…

Acid-base titrations for polyacids: Significance of the pK sub a and parameters in the Kern equation

NASA Technical Reports Server (NTRS)

Meites, L.

1978-01-01

A new method is suggested for calculating the dissociation constants of polyvalent acids, especially polymeric acids. In qualitative form the most significant characteristics of the titration curves are demonstrated and identified which are obtained when titrating the solutions of such acids with a standard base potentiometrically.

Complexation Key to a pH Locked Redox Reaction

ERIC Educational Resources Information Center

Rizvi, Masood Ahmad; Dangat, Yuvraj; Shams, Tahir; Khan, Khaliquz Zaman

2016-01-01

An unfavorable pH can block a feasible electron transfer for a pH dependent redox reaction. In this experiment, a series of potentiometric titrations demonstrate the sequential loss in feasibility of iron(II) dichromate redox reaction over a pH range of 0-4. The pH at which this reaction failed to occur was termed as a pH locked reaction. The…

FTIR studies of the redox partner interaction in cytochrome P450: the Pdx-P450cam couple.

PubMed

Karyakin, Andrey; Motiejunas, Domantas; Wade, Rebecca C; Jung, Christiane

2007-03-01

Recently we have developed a new approach to study protein-protein interactions using Fourier transform infrared spectroscopy in combination with titration experiments and principal component analysis (FTIR-TPCA). In the present paper we review the FTIR-TPCA results obtained for the interaction between cytochrome P450 and the redox partner protein in two P450 systems, the Pseudomonas putida P450cam (CYP101) with putidaredoxin (P450cam-Pdx), and the Bacillus megaterium P450BM-3 (CYP102) heme domain with the FMN domain (P450BMP-FMND). Both P450 systems reveal similarities in the structural changes that occur upon redox partner complex formation. These involve an increase in beta-sheets and alpha-helix content, a decrease in the population of random coil/3(10)-helix structure, a redistribution of turn structures within the interacting proteins and changes in the protonation states or hydrogen-bonding of amino acid carboxylic side chains. We discuss in detail the P450cam-Pdx interaction in comparison with literature data and conclusions drawn from experiments obtained by other spectroscopic techniques. The results are also interpreted in the context of a 3D structural model of the Pdx-P450cam complex.

A new crystal structure of the bifunctional antibiotic simocyclinone D8 bound to DNA gyrase gives fresh insight into the mechanism of inhibition.

PubMed

Hearnshaw, Stephen J; Edwards, Marcus J; Stevenson, Clare E; Lawson, David M; Maxwell, Anthony

2014-05-15

Simocyclinone D8 (SD8) is an antibiotic produced by Streptomyces antibioticus that targets DNA gyrase. A previous structure of SD8 complexed with the N-terminal domain of the DNA gyrase A protein (GyrA) suggested that four SD8 molecules stabilized a tetramer of the protein; subsequent mass spectrometry experiments suggested that a protein dimer with two symmetry-related SD8s was more likely. This work describes the structures of a further truncated form of the GyrA N-terminal domain fragment with and without SD8 bound. The structure with SD8 has the two SD8 molecules bound within the same GyrA dimer. This new structure is entirely consistent with the mutations in GyrA that confer SD8 resistance and, by comparison with a new apo structure of the GyrA N-terminal domain, reveals the likely conformation changes that occur upon SD8 binding and the detailed mechanism of SD8 inhibition of gyrase. Isothermal titration calorimetry experiments are consistent with the crystallography results and further suggest that a previously observed complex between SD8 and GyrB is ~1000-fold weaker than the interaction with GyrA. Copyright © 2014. Published by Elsevier Ltd.

A New Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8 Bound to DNA Gyrase Gives Fresh Insight into the Mechanism of Inhibition

PubMed Central

Hearnshaw, Stephen J.; Edwards, Marcus J.; Stevenson, Clare E.; Lawson, David M.; Maxwell, Anthony

2014-01-01

Simocyclinone D8 (SD8) is an antibiotic produced by Streptomyces antibioticus that targets DNA gyrase. A previous structure of SD8 complexed with the N-terminal domain of the DNA gyrase A protein (GyrA) suggested that four SD8 molecules stabilized a tetramer of the protein; subsequent mass spectrometry experiments suggested that a protein dimer with two symmetry-related SD8s was more likely. This work describes the structures of a further truncated form of the GyrA N-terminal domain fragment with and without SD8 bound. The structure with SD8 has the two SD8 molecules bound within the same GyrA dimer. This new structure is entirely consistent with the mutations in GyrA that confer SD8 resistance and, by comparison with a new apo structure of the GyrA N-terminal domain, reveals the likely conformation changes that occur upon SD8 binding and the detailed mechanism of SD8 inhibition of gyrase. Isothermal titration calorimetry experiments are consistent with the crystallography results and further suggest that a previously observed complex between SD8 and GyrB is ~ 1000-fold weaker than the interaction with GyrA. PMID:24594357

Mistaking the recent past for the present: false seeing by older adults.

PubMed

Jacoby, Larry L; Rogers, Chad S; Bishara, Anthony J; Shimizu, Yujiro

2012-03-01

Results of three experiments revealed that older, as compared to young, adults are more reliant on context when "seeing" a briefly flashed word that was preceded by a prime. In a congruent condition, the prime was the same word as flashed (e.g., DIRT dirt) whereas in an incongruent condition, the prime differed in a single letter from the word that was flashed (DART dirt). Following their attempt to identify the flashed word, participants were asked to report whether they had "seen" the flashed word or, instead, had responded on some other basis (knowing or guessing). Older adults showed dramatically higher false seeing by reporting the prime on incongruent trials and claiming to have seen it flashed. This was true even though a titration procedure was used to equate the performance of young and older adults on baseline trials which did not provide a biasing context. Results of Experiment 3 related age differences in false seeing to willingness to respond when given the option to withhold responses. Convergence of results with those showing higher false memory and false hearing are interpreted as evidence that older adults are less able to avoid misleading effects of context. That lessened ability may be associated with decline in frontal lobe functioning.

Cooperativity and tunable excited state deactivation: modular self-assembly of depsipeptide dendrons on a Hamilton receptor modified porphyrin platform.

PubMed

Gnichwitz, Jan-Frederik; Wielopolski, Mateusz; Hartnagel, Kristine; Hartnagel, Uwe; Guldi, Dirk M; Hirsch, Andreas

2008-07-02

A series of novel supramolecular architectures were built around a tin tetraphenyl porphyrin platform 6--functionalized by a 2-fold 1-ethyl-3-3-(3-dimethylaminopropyl)carbodiimide (EDC) promoted condensation reaction--and chiral depsipeptide dendrons of different generations 1-4. Here, implementation of a Hamilton receptor provided the necessary means to keep the constituents together via strong hydrogen bonding. Characterization of all architectures has been performed, including 4 which is the fourth generation, on the basis of NMR and photophysical methods. In particular, several titration experiments were conducted suggesting positive cooperativity, an assessment that is based on association constants that tend to be higher for the second binding step than for the first step. Importantly, molecular modeling calculations reveal a significant deaggregation of the intermolecular network of 6 during the course of the first binding step. As a consequence, an improved accessibility of the second Hamilton receptor unit in 6 emerges and, in turn, facilitates the higher association constants. The features of the equilibrium, that is, the dynamic exchange of depsipeptide dendrons 1-4 with fullerene 5, was tested in photophysical reference experiments. These steady-state and time-resolved measurements showed the tunable excited-state deactivations of these complexes upon photoexcitation.

Structural properties of the promiscuous VP16 activation domain.

PubMed

Jonker, Hendrik R A; Wechselberger, Rainer W; Boelens, Rolf; Folkers, Gert E; Kaptein, Rob

2005-01-25

Herpes simplex virion protein 16 (VP16) contains two strong activation regions that can independently and cooperatively activate transcription in vivo. We have identified the regions and residues involved in the interaction with the human transcriptional coactivator positive cofactor 4 (PC4) and the general transcription factor TFIIB. NMR and biochemical experiments revealed that both VP16 activation regions are required for the interaction and undergo a conformational transition from random coil to alpha-helix upon binding to its target PC4. The interaction is strongly electrostatically driven and the binding to PC4 is enhanced by the presence of its amino-terminal domain. We propose models for binding of VP16 to the core domains of PC4 and TFIIB that are based on two independent docking approaches using NMR chemical shift changes observed in titration experiments. The models are consistent with results from site-directed mutagenesis and provide an explanation for the contribution of both acidic and hydrophobic residues for transcriptional activation by VP16. Both intrinsically unstructured activation domains are attracted to their interaction partner by electrostatic interactions, and adopt an alpha-helical conformation around the important hydrophobic residues. The models showed multiple distinct binding surfaces upon interaction with various partners, providing an explanation for the promiscuous properties, cooperativity, and the high activity of this activation domain.

Improving medication titration in heart failure by embedding a structured medication titration plan.

PubMed

Hickey, Annabel; Suna, Jessica; Marquart, Louise; Denaro, Charles; Javorsky, George; Munns, Andrew; Mudge, Alison; Atherton, John J

2016-12-01

To improve up-titration of medications to target dose in heart failure patients by improving communication from hospital to primary care. This quality improvement project was undertaken within three heart failure disease management (HFDM) services in Queensland, Australia. A structured medication plan was collaboratively designed and implemented in an iterative manner, using methods including awareness raising and education, audit and feedback, integration into existing work practice, and incentive payments. Evaluation was undertaken using sequential audits, and included process measures (use of the titration plan, assignment of responsibility) and outcome measures (proportion of patients achieving target dose) in HFDM service patients with reduced left ventricular ejection fraction. Comparison of the three patient cohorts (pre-intervention cohort A n=96, intervention cohort B n=95, intervention cohort C n=89) showed increase use of the titration plan, a shift to greater primary care responsibility for titration, and an increase in the proportion of patients achieving target doses of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) (A 37% vs B 48% vs C 55%, p=0.051) and beta-blockers (A 38% vs B 33% vs C 51%, p=0.045). Combining all three cohorts, patients not on target doses when discharged from hospital were more likely to achieve target doses of ACEI/ARB (p<0.0001) and beta blockers (p<0.0001) within six months if they received a medication titration plan. A medication titration plan was successfully implemented in three HFDM services and improved transitional communication and achievement of target doses of evidence-based therapies within six months of hospital discharge. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Does a patient-managed insulin intensification strategy with insulin glargine and insulin glulisine provide similar glycemic control as a physician-managed strategy? Results of the START (Self-Titration With Apidra to Reach Target) Study: a randomized noninferiority trial.

PubMed

Harris, Stewart B; Yale, Jean-François; Berard, Lori; Stewart, John; Abbaszadeh, Babak; Webster-Bogaert, Susan; Gerstein, Hertzel C

2014-01-01

OBJECTIVE Diabetes self-management is universally regarded as a foundation of diabetes care. We determined whether comparable glycemic control could be achieved by self-titration versus physician titration of a once-daily bolus insulin dose in patients with type 2 diabetes who are unable to achieve optimal glycemia control with a basal insulin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes, an HbA1c level >7% (53 mmol/mol), and either nocturnal hypoglycemia episodes or an insufficient basal insulin glargine level (with or without oral agents) to achieve a fasting plasma glucose level ≤6 mmol/L (108 mg/dL) were studied. Participants all had bolus insulin glulisine added at breakfast and were allocated to either algorithm-guided patient self-titration or physician titration. The primary outcome was an HbA1c level ≤7% (53 mmol/mol) without severe hypoglycemia. RESULTS After a mean (SD) follow-up of 159.4 days (36.2 days), 28.4% of participants in the self-titration arm vs. 21.2% in the physician titration arm achieved an HbA1c level of ≤7% (53 mmol/mol) without severe hypoglycemia (between-group absolute difference 7.2%; 95% CI -3.2 to 17.7). The lower end of this 95% confidence interval was within the predetermined noninferiority boundary of -5% (P noninferiority = 0.011). CONCLUSIONS In stable patients with type 2 diabetes who are receiving doses of basal insulin glargine who require bolus insulin, a simple bolus insulin patient-managed titration algorithm is as effective as a physician-managed algorithm.

Rapid clozapine titration in treatment-refractory bipolar disorder.

PubMed

Ifteni, Petru; Correll, Christoph U; Nielsen, Jimmi; Burtea, Victoria; Kane, John M; Manu, Peter

2014-09-01

Clozapine is effective in treatment-refractory bipolar disorder (BD). Guidelines recommend slow titration to prevent seizures, hypotension and myocarditis, but this stance is not supported by comparative data. To evaluate the safety and effectiveness of rapid clozapine titration in BD. Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital. On one unit, clozapine was started at 25mg followed by 25-50mg as needed every 6h (maximum=100mg/day) on day 1, followed by increases of 25-100mg/day. On the other unit, clozapine was initiated with 25mg in day 1, followed by increases of 25-50mg/day. The primary outcome was the number of days from starting clozapine until readiness for discharge, adjusted in logistic regression for the number of antipsychotics tried during the hospitalization, psychotropic co-treatments and presence of psychotic features. Patients subject to rapid (N=44) and standard (N=23) titration were similar in age, gender, smoking status, body mass index, illness severity at baseline and discharge, and highest clozapine dose. Clozapine was discontinued due to hypotension (N=1) and pneumonia (N=1) during rapid titration, and for excessive sedation (N=1) in each titration group. The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group (12.7±6.3 vs. 16.5±5.8, p=0.0077). Rapid clozapine titration appeared safe and effective for treatment-refractory BD. The potential for shorter hospital stays justifies prospective trials of this method. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical, polysomnographic, and CPAP titration features of obstructive sleep apnea: Mixed versus purely obstructive type.

PubMed

Lee, Sang-Ahm; Lee, Gha-Hyun; Chung, Yoo-Sam; Kim, Woo Sung

2015-08-15

To determine whether obstructive sleep apnea syndrome (OSAS) patients with mixed sleep apnea (MSA) have different clinical, polysomnographic, and continuous positive airway pressure (CPAP) titration findings compared to OSAS patients without MSA. We retrospectively reviewed the records of OSAS patients who had undergone CPAP titration and categorized them into pure-OSA and mixed-OSA groups. Demographic features, daytime sleepiness, and apnea severity were compared between the two groups using univariate and multivariate analyses. CPAP titration findings were also compared between the two groups. One hundred and ninety-five subjects (n=126 pure-OSA; n=69 mixed-OSA) were included in the analysis. Compared to the pure-OSA group, the mixed-OSA group had a higher percentage of males (p=0.003) and a higher body mass index (p=0.044), Epworth Sleepiness Scale score (p=0.028), and apnea-hypopnea index (AHI) (p<0.001). In logistic regression analysis, older age, male sex, and higher body mass index were independently associated with mixed-OSA before PSG study. When using AHI as a covariable, the higher AHI with older age, male sex, and daytime sleepiness was independently related to mixed-OSA. The mixed-OSA group had a higher percentage of patients with complex sleep apnea, a lower percentage of patients with optimal titration, and a higher titrated pressure than the pure-OSA group. Severe OSA, older age, male sex, obesity, and daytime sleepiness were related to mixed-OSA. Complex sleep apnea, less optimal titration, and a higher titrated CPAP were also associated with MSA in OSAS patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Fluorometric titration approach for calibration of quantity of binding site of purified monoclonal antibody recognizing epitope/hapten nonfluorescent at 340 nm.

PubMed

Yang, Xiaolan; Hu, Xiaolei; Xu, Bangtian; Wang, Xin; Qin, Jialin; He, Chenxiong; Xie, Yanling; Li, Yuanli; Liu, Lin; Liao, Fei

2014-06-17

A fluorometric titration approach was proposed for the calibration of the quantity of monoclonal antibody (mcAb) via the quench of fluorescence of tryptophan residues. It applied to purified mcAbs recognizing tryptophan-deficient epitopes, haptens nonfluorescent at 340 nm under the excitation at 280 nm, or fluorescent haptens bearing excitation valleys nearby 280 nm and excitation peaks nearby 340 nm to serve as Förster-resonance-energy-transfer (FRET) acceptors of tryptophan. Titration probes were epitopes/haptens themselves or conjugates of nonfluorescent haptens or tryptophan-deficient epitopes with FRET acceptors of tryptophan. Under the excitation at 280 nm, titration curves were recorded as fluorescence specific for the FRET acceptors or for mcAbs at 340 nm. To quantify the binding site of a mcAb, a universal model considering both static and dynamic quench by either type of probes was proposed for fitting to the titration curve. This was easy for fitting to fluorescence specific for the FRET acceptors but encountered nonconvergence for fitting to fluorescence of mcAbs at 340 nm. As a solution, (a) the maximum of the absolute values of first-order derivatives of a titration curve as fluorescence at 340 nm was estimated from the best-fit model for a probe level of zero, and (b) molar quantity of the binding site of the mcAb was estimated via consecutive fitting to the same titration curve by utilizing such a maximum as an approximate of the slope for linear response of fluorescence at 340 nm to quantities of the mcAb. This fluorometric titration approach was proved effective with one mcAb for six-histidine and another for penicillin G.

Titration ELISA as a Method to Determine the Dissociation Constant of Receptor Ligand Interaction.

PubMed

Eble, Johannes A

2018-02-15

The dissociation constant describes the interaction between two partners in the binding equilibrium and is a measure of their affinity. It is a crucial parameter to compare different ligands, e.g., competitive inhibitors, protein isoforms and mutants, for their binding strength to a binding partner. Dissociation constants are determined by plotting concentrations of bound versus free ligand as binding curves. In contrast, titration curves, in which a signal that is proportional to the concentration of bound ligand is plotted against the total concentration of added ligand, are much easier to record. The signal can be detected spectroscopically and by enzyme-linked immunosorbent assay (ELISA). This is exemplified in a protocol for a titration ELISA that measures the binding of the snake venom-derived rhodocetin to its immobilized target domain of α2β1 integrin. Titration ELISAs are versatile and widely used. Any pair of interacting proteins can be used as immobilized receptor and soluble ligand, provided that both proteins are pure, and their concentrations are known. The difficulty so far has been to determine the dissociation constant from a titration curve. In this study, a mathematical function underlying titration curves is introduced. Without any error-prone graphical estimation of a saturation yield, this algorithm allows processing of the raw data (signal intensities at different concentrations of added ligand) directly by mathematical evaluation via non-linear regression. Thus, several titration curves can be recorded simultaneously and transformed into a set of characteristic parameters, among them the dissociation constant and the concentration of binding-active receptor, and they can be evaluated statistically. When combined with this algorithm, titration ELISAs gain the advantage of directly presenting the dissociation constant. Therefore, they may be used more efficiently in the future.

Determination of the titratable acidity and the pH of wine based on potentiometric flow injection analysis.

PubMed

Vahl, Katja; Kahlert, Heike; von Mühlen, Lisandro; Albrecht, Anja; Meyer, Gabriele; Behnert, Jürgen

2013-07-15

A FIA system using a pH-sensitive detector based on a graphite/quinhydrone/silicone composite electrode was applied to determine sequentially the titratable acidity and the pH of wine, as well as the sum of calcium and magnesium ions. For all measurements the same FIA configuration was used employing different carrier solutions. The results for the determination of acidity and pH are in good agreement with those obtained by classical potentiometric titrations and by pH measurements using a conventional glass electrode. The standard deviation was less than 1.5% for both kinds of measurements and the sample volume was 150 μL. The method allows about 40 determinations of titratable acidity per hour and 30 pH measurements per hour. The titration method can be adjusted to the legal requirements in USA and Europe. Copyright © 2013 Elsevier B.V. All rights reserved.

A Laser-Pointer-Based Spectrometer for Endpoint Detection of EDTA Titrations

ERIC Educational Resources Information Center

Dahm, Christopher E.; Hall, James W.; Mattioni, Brian E.

2004-01-01

A laser spectrometer for the ethylenediaminetetra-acetic acid (EDTA) titration of magnesium or calcium ions that is designed around a handheld laser pointer as the source and a photoresistor as the detector is developed. Findings show that the use of the spectrometer reduces the degree of uncertainty and error in one part of the EDTA titrations,…

Influence of kinetics on the determination of the surface reactivity of oxide suspensions by acid-base titration.

PubMed

Duc, M; Adekola, F; Lefèvre, G; Fédoroff, M

2006-11-01

The effect of acid-base titration protocol and speed on pH measurement and surface charge calculation was studied on suspensions of gamma-alumina, hematite, goethite, and silica, whose size and porosity have been well characterized. The titration protocol has an important effect on surface charge calculation as well as on acid-base constants obtained by fitting of the titration curves. Variations of pH versus time after addition of acid or base to the suspension were interpreted as diffusion processes. Resulting apparent diffusion coefficients depend on the nature of the oxide and on its porosity.

Study of the acid-base properties of mineral soil horizons using pK spectroscopy

NASA Astrophysics Data System (ADS)

Shamrikova, E. V.; Vanchikova, E. V.; Ryazanov, M. A.

2007-11-01

The presence of groups 4 and 5 participating in acid-base equilibria was revealed in samples from mineral horizons of the gley-podzolic soil of the Komi Republic using pK spectroscopy (the mathematical processing of potentiometric titration curves for plotting the distribution of acid groups according to their pK values). The specific quantity of acid-base sites in soil samples was calculated. The contribution of organic and mineral soil components to the groups of acid-base sites was estimated. The pK values of groups determining the potential, exchangeable, and unexchangeable acidities were found. The heterogeneity of acid components determining different types of soil acidity was revealed.

Determination of the intrinsic redox potentials of FeS centers of respiratory complex I from experimental titration curves

PubMed Central

Medvedev, Emile S.; Couch, Vernon A.

2014-01-01

Recently, Euro et al. [Biochem. 47, 3185 (2008)] have reported titration data for seven of nine FeS redox centers of complex I from E. coli. There is a significant uncertainty in the assignment of the titration data. Four of the titration curves were assigned to N1a, N1b, N6b, and N2 centers; one curve either to N3 or N7; one more either to N4 or N5; and the last one denoted Nx could not be assigned at all. In addition, the assignment of the titration data to N6b/N6a pair is also uncertain. In this paper, using our calculated interaction energies [Couch et al. BBA 1787, 1266 (2009)], we perform statistical analysis of these data, considering a variety of possible assignments, find the best fit, and determine the intrinsic redox potentials of the centers. The intrinsic potentials could be determined with uncertainty of less than ±10 mV at 95% confidence level for best fit assignments. We also find that the best agreement between theoretical and experimental titration curves is obtained with the N6b-N2 interaction equal to 71±14 or 96±26 mV depending on the N6b/N6a titration data assignment, which is stronger than was expected and may indicate a close distance of N2 center to the membrane surface. PMID:20513348

Non-Aqueous Titration Method for Determining Suppressor Concentration in the MCU Next Generation Solvent (NGS)

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

Taylor-Pashow, Kathryn M. L.; Jones, Daniel H.

A non-aqueous titration method has been used for quantifying the suppressor concentration in the MCU solvent hold tank (SHT) monthly samples since the Next Generation Solvent (NGS) was implemented in 2013. The titration method measures the concentration of the NGS suppressor (TiDG) as well as the residual tri-n-octylamine (TOA) that is a carryover from the previous solvent. As the TOA concentration has decreased over time, it has become difficult to resolve the TiDG equivalence point as the TOA equivalence point has moved closer. In recent samples, the TiDG equivalence point could not be resolved, and therefore, the TiDG concentration wasmore » determined by subtracting the TOA concentration as measured by semi-volatile organic analysis (SVOA) from the total base concentration as measured by titration. In order to improve the titration method so that the TiDG concentration can be measured directly, without the need for the SVOA data, a new method has been developed that involves spiking of the sample with additional TOA to further separate the two equivalence points in the titration. This method has been demonstrated on four recent SHT samples and comparison to results obtained using the SVOA TOA subtraction method shows good agreement. Therefore, it is recommended that the titration procedure be revised to include the TOA spike addition, and this to become the primary method for quantifying the TiDG.« less

Treatment discontinuation and tolerability as a function of dose and titration of duloxetine in the treatment of major depressive disorder.

PubMed

Harada, Eiji; Shirakawa, Osamu; Satoi, Yoichi; Marangell, Lauren B; Escobar, Rodrigo

2016-01-01

We sought to better understand how dose and titration with duloxetine treatment may impact tolerability and treatment discontinuation in patients with major depressive disorder. We investigated Phase III duloxetine trials. Group 1 was a single placebo-controlled study with a 20 mg initial dose and a slow titration to 40 and 60 mg. Group 2 was a single study with a 40 mg initial dose and final "active" doses of 40 and 60 mg (5 mg control group), with 1-week titration. Group 3 consisted of eight placebo-controlled studies with starting doses of 40, 60, and 80 mg/day with minimal titration (final dose 40-120 mg/day). Tolerability was measured by rate of discontinuation due to adverse events (DCAE). The DCAE in Group 1 were 3.6% in the 60 mg group, 3.3% in the 40 mg group, and 3.2% in the placebo group. In Group 2, the DCAE were 15.0% in the 60 mg group, 8.1% in the 40 mg group, and 4.9% in the 5 mg group. In Group 3, the DCAE were 9.7% and 4.2% in the duloxetine and placebo groups, respectively. This study suggests that starting dose and titration may have impacted tolerability and treatment discontinuation. A lower starting dose of duloxetine and slower titration may contribute to improving treatment tolerability for patients with major depressive disorder.

Dose titration of repaglinide in patients with inadequately controlled type 2 diabetes.

PubMed

Kølendorf, Klaus; Eriksson, Johan; Birkeland, Kåre I; Kjellström, Thomas; Hreidarsson, Astradur B

2004-04-01

A total of 385 drug-therapy naïve patients, with inadequately controlled type 2 diabetes, were randomised into a multinational, parallel-group study to compare two strategies for dose titration of the oral hypoglycaemic agent repaglinide. Patients were allocated to either a fasting blood glucose (FBG) monitoring group with titration target 4.4-6.1 mmol/l or to a post-prandial blood glucose (PPBG) monitoring group with titration target 4.4-8.0 mmol/l. An initial titration period of up to 8 weeks was followed by a 12-week treatment period. Glycaemic control and hypoglycaemic outcomes were compared for the respective groups. HbA(1c) decreased significantly more in the FBG monitoring group by a mean of 1.38% compared to the PPBG group by a mean of 1.22% (P=0.03). The glycaemic control targets were met by fewer patients in the FBG group than in the PPBG group (57% versus 86% (P<0.001)) despite a higher mean dose of repaglinide in the FBG group. The within-patient blood glucose variability was significantly lower in the FBG group than in the PPBG group (P<0.001). In conclusion, repaglinide lowered the HbA(1c) effectively and safely in both groups and self-monitored FBG is a suitable parameter for titration of repaglinide. Whether a lower PPBG target might be as good a guide as FBG for titration of repaglinide should be addressed in a future study.

Prescribing and up-titration in recently hospitalized heart failure patients attending a disease management program.

PubMed

Carroll, Robert; Mudge, Alison; Suna, Jessica; Denaro, Charles; Atherton, John

2016-08-01

Heart failure (HF) medications improve clinical outcomes, with optimal doses defined in clinical trials. Patient, provider and system barriers may limit achievement of optimal doses in real life settings, although disease management programs (HF-DMPs) can facilitate up-titration. Secondary analysis of a prospective cohort of 216 participants recently hospitalized with systolic HF, attending 5 HF-DMPs in Queensland, Australia. Medication history at baseline (6weeks after discharge) and 6months provided data to describe prescription rates, dosage and optimal titration of HF medications, and associations with patient and system factors were explored. At baseline, 94% were on an angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB), 94% on a beta-blocker (BB) and 42% on a mineralocorticoid receptor antagonist (MRA). The proportion of participants on optimal doses of ACEI/ARB increased from 38% (baseline) to 52% (6months, p=0.001) and on optimal BB dose from 23% to 49% (p<0.001). Significant barriers to ACEI/ARB up-titration were body mass index (BMI)<25, female gender, polypharmacy, previously diagnosed HF, and tertiary hospital. Significant barriers for BB up-titration were BMI<25, previously diagnosed HF and non-cardiologist care. Effective up-titration in HF DMPs is influenced by patient, disease and service factors. Better understanding of barriers to effective up-titration in women, normal weight, and established HF patients may help provide targeted strategies for improving outcomes in these groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

Patient emotions and perceptions of antiepileptic drug changes and titration during treatment for epilepsy.

PubMed

Fishman, Jesse; Cohen, Greg; Josephson, Colin; Collier, Ann Marie; Bharatham, Srikanth; Zhang, Ying; Wild, Imane

2017-04-01

To investigate the impact of antiepileptic drug (AED) change and dose titration on the emotional well-being of patients with epilepsy. Members of an online epilepsy community were invited to voluntarily participate in an online survey. The cross-sectional anonymous survey consisted of 31 multiple choice questions balanced in terms of variety and positivity/negativity of emotions concerning participants' most recent AED change. To substantiate survey results, spontaneous comments from epilepsy-related online forums and social media websites that mentioned participants' experiences with AED medication changes (termed passive listening statements) were analyzed and categorized by theme. All 345 survey participants (270 [78.3%] female; 172 [49.9%] were 26-45years old) self-reported an epilepsy/seizure diagnosis and were currently taking seizure medication; 263 (76.2%) were taking ≥2 AEDs and 301 (87.2%) had ≥1 seizure in the previous 18months. All participants reported a medication change within the previous 12months (dose increased [153 participants (44.3%)], medication added [105 (30.4%)], dose decreased [49 (14.2%)], medication removed [38 (11.0%)]). Improving seizure control (247 [71.6%]) and adverse events (109 [31.6%]) were the most common reasons for medication change. Primary emotions most associated (≥10% of participants) with an AED regimen change were (before medication change; during/after medication change) hopefulness (50 [14.5%]; 43 [12.5%]), uncertainty (50 [14.5%]; 69 [20.0%]), and anxiety (35 [10.1%]; 45 [13.0%]), and were largely due to concerns whether the change would work (212/345 [61.4%]; 180/345 [52.2%]). In the text analysis segment aimed at validating the survey, 230 participants' passive listening statements about medication titration were analyzed; additional seizure activity during dose titration (93 [40.4%]), adverse events during titration (71 [30.9%]), higher medication dosages (33 [14.3%]), and drug costs (25 [10.9%]) were the most commonly noted concerns. Although the emotional well-being of patients with epilepsy is complex, our study results suggest that participants report their emotional well-being as negatively affected by changes in AED regimen, with most patients reporting uncertainty regarding the outcome of such a change. Future research is warranted to explore approaches to alleviate patient concerns associated with AED medication changes. Copyright © 2017 Ellen Carey, UCB Brussels, Belgium. Published by Elsevier Inc. All rights reserved.

A double-blind, randomized study evaluating losartan potassium monotherapy or in combination with hydrochlorothiazide versus placebo in obese patients with hypertension.

PubMed

Oparil, S; Abate, N; Chen, E; Creager, M A; Galet, V; Jia, G; Julius, S; Lerman, A; Lyle, P A; Pool, J; Tershakovec, A M

2008-04-01

The objective of this study was to evaluate the effects of losartan +/- hydrochlorothiazide (HCTZ) versus placebo in obese patients with systolic and diastolic hypertension. Randomized patients (n = 261) were non-diabetic with systolic blood pressure (SBP) > or = 140 and < or = 180 mmHg and diastolic BP (DBP) > or = 95 and < or = 115 mmHg, body mass index > 30 kg/m(2), and waist circumference > 40 (males)/> 35 (females) inches. Patients were randomized to placebo or a forced titration of losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/HCTZ 12.5 mg, and losartan 100 mg/HCTZ 25 mg. Primary efficacy measurements were change from baseline in SBP and DBP at 12 weeks. Secondary measurements were change from baseline in BPs at 8 and 16 weeks, percent responders at 12 and 16 weeks, and safety/tolerability. Post-hoc analyses were BP at 4 weeks and achievement of controlled BP (SBP < 140 and/or DBP < 90 mmHg) at 12 and 16 weeks. Losartan 50 mg reduced BP from 151.6/99.2 mmHg at baseline to 140.1/89.8 mmHg at week 4 (post hoc), 139.5/89.6 mmHg with losartan 100 mg at week 8 (secondary), 134.3/85.9 mmHg with losartan 100 mg/HCTZ 12.5 mg at week 12 (primary), and 132.1/84.9 mmHg with losartan 100 mg/HCTZ 50 mg at week 16 (secondary) (all p < 0.05). Rates of clinical adverse experiences were similar between treatment groups. A limitation of these analyses is the relatively rapid rate of study drug titration, which may not have allowed for the evaluation of the full treatment effect at each titration step. We conclude that losartan alone or in combination with HCTZ was generally well tolerated and effective in the treatment of elevated systolic and diastolic BP in obese patients with hypertension.

Chelating effect of citric acid is negligible for development of enamel erosions.

PubMed

Azadi-Schossig, Parastu; Becker, Klaus; Attin, Thomas

2016-09-01

Citric acid (CA) is a component in beverages responsible for dental erosion. The aim of this study was to examine the influence of CA with different pH, titratable acid and buffer capacity (ß), and the impact of the chelating effect of CA on development of enamel erosions. In a superfusion model, hydroxy apatite (HAp) dissolution of bovine enamel was measured in four experiments (EXP 1-4) with 27 experimental groups (n = 8 per group). The samples were superfused with different CA variations and respective controls. EXP-1: Dilution series of HCl (pH 2.15-3.02). EXP-2: Dilution series of natural CA (56-1.75 mmol l(-1); pH 2.15-3.02). EXP-3: CA solutions (56 and 14 mmol l(-1), ß: 39.7 and 10.2 mmol l(-1) pH(-1), respectively) with different titratable acidity at equal pH values. EXP-4: CA concentrations (56-1.75 mmol l(-1)) neutralized to pH 7. CA led to higher HAp-dissolution than HCl. With higher pH, the difference in HAp-dissolution rate between the two acids became increasingly smaller. At equal pH, HAp-dissolution was higher for the CA with the higher amount of titratable acid. However, no clear correlation between erosion and titratable acid or ß could be found. Only minimal amounts of HAp were dissolved by neutralized CA compared to CA with natural pH. Under the chosen conditions chelating effects of CA do not have a relevant influence of HAp-dissolution of enamel. Moreover, amount of HAp-dissolution by CA is not attributed to a single factor alone. The interplay between the different parameters of CA seems to be responsible for its erosive potential. The erosive potential of solutions containing citric acid with unknown concentrations could not be predicted using a single parameter alone, and should at best determined in experimental set-ups.

Effect of aluminum, zinc, copper, and lead on the acid-base properties of water extracts from soils

NASA Astrophysics Data System (ADS)

Motuzova, G. V.; Makarychev, I. P.; Petrov, M. I.

2013-01-01

The potentiometric titration of water extracts from the upper horizons of taiga-zone soils by salt solutions of heavy metals (Pb, Cu, and Zn) showed that their addition is an additional source of the extract acidity because of the involvement of the metal ions in complexation with water-soluble organic substances (WSOSs). At the addition of 0.01 M water solutions of Al(NO3)3 to water extracts from soils, Al3+ ions are also involved in complexes with WSOSs, which is accompanied by stronger acidification of the extracts from the upper horizon of soddy soils (with a near-neutral reaction) than from the litter of bog-podzolic soil (with a strongly acid reaction). The effect of the Al3+ hydrolysis on the acidity of the extracts is insignificantly low in both cases. A quantitative relationship was revealed between the release of protons and the ratio of free Cu2+ ions to those complexed with WSOSs at the titration of water extracts from soils by a solution of copper salt.

Analytical methods to determine the comparative DNA binding studies of curcumin-Cu(II) complexes

NASA Astrophysics Data System (ADS)

Rajesh, Jegathalaprathaban; Rajasekaran, Marichamy; Rajagopal, Gurusamy; Athappan, Periakaruppan

2012-11-01

DNA interaction studies of two mononuclear [1:1(1); 1:2(2)] copper(II) complexes of curcumin have been studied. The interaction of these complexes with CT-DNA has been explored by physical methods to propose modes of DNA binding of the complexes. Absorption spectral titrations of complex 1 with CT-DNA shows a red-shift of 3 nm with the DNA binding affinity of Kb, 5.21 × 104 M-1 that are higher than that obtained for 2 (red-shift, 2 nm; Kb, 1.73 × 104 M-1) reveal that the binding occurs in grooves as a result of the interaction is via exterior phosphates. The CD spectra of these Cu(II) complexes show a red shift of 3-10 nm in the positive band with increase in intensities. This spectral change of induced CD due to the hydrophobic interaction of copper complexes with DNA is the characteristic of B to A conformational change. The EB displacement assay also reveals the same trend as observed in UV-Vis spectral titration. The addition of complexes 1 and 2 to the DNA bound ethidium bromide (EB) solutions causes an obvious reduction in emission intensities indicating that these complexes competitively bind to DNA with EB. The positive shift of both the Epc and E0' accompanied by reduction of peak currents in differential pulse voltammogram (DPV), upon adding different concentrations of DNA to the metal complexes, are obviously in favor of strong binding to DNA. The super coiled plasmid pUC18 DNA cleavage ability of Cu(II) complexes in the presence of reducing agent reveals the single strand DNA cleavage (ssDNA) is observed. The hydroxyl radical (HOrad ) and the singlet oxygen are believed to be the reactive species responsible for the cleavage.

Concurrent determination of total serum calcium and magnesium by thermometric titration with ethylenediaminetetraacetate.

PubMed

Callicott, R H; Carr, P W

1976-07-01

Total serum calcium and magnesium may be determined in one thermometric titration, with disodium ethylenediaminetetraacetate as the titrant. A 1-ml serum sample is diluted with 1 ml of tris(hydroxymethyl)aminomethane buffer (pH 8) and titrated at a constant rate with a motorized syringe buret. Results by the thermometric method compared well with those by atomic absorption spectroscopy.

Randomized clinical trial of an intravenous hydromorphone titration protocol versus usual care for management of acute pain in older emergency department patients.

PubMed

Chang, Andrew K; Bijur, Polly E; Davitt, Michelle; Gallagher, E John

2013-09-01

Opioid titration is an effective strategy for treating pain; however, titration is generally impractical in the busy emergency department (ED) setting. Our objective was to test a rapid, two-step, hydromorphone titration protocol against usual care in older patients presenting to the ED with acute severe pain. This was a prospective, randomized clinical trial of patients 65 years of age and older presenting to an adult, urban, academic ED with acute severe pain. The study was registered at http://www.clinicaltrials.gov (NCT01429285). Patients randomized to the hydromorphone titration protocol initially received 0.5 mg intravenous hydromorphone. Patients randomized to usual care received any dose of any intravenous opioid. At 15 min, patients in both groups were asked, 'Do you want more pain medication?' Patients in the hydromorphone titration group who answered 'yes' received a second dose of 0.5 mg intravenous hydromorphone. Patients in the usual care group who answered 'yes' had their ED attending physician notified, who then could administer any (or no) additional medication. The primary efficacy outcome was satisfactory analgesia defined a priori as the patient declining additional analgesia at least once when asked at 15 or 60 min after administration of the initial opioid. Dose was calculated in morphine equivalent units (MEU: 1 mg hydromorphone = 7 mg morphine). The need for naloxone to reverse adverse opioid effects was the primary safety outcome. 83.0 % of 153 patients in the hydromorphone titration group achieved satisfactory analgesia compared with 82.5 % of 166 patients in the usual care group (p = 0.91). Patients in the hydromorphone titration group received lower mean initial doses of opioids at baseline than patients in the usual care group (3.5 MEU vs. 4.7 MEU, respectively; p ≤ 0.001) and lower total opioids through 60 min (5.3 MEU vs. 6.0 MEU; p = 0.03). No patient needed naloxone. Low-dose titration of intravenous hydromorphone in increments of 0.5 mg provides comparable analgesia to usual care with less opioid over 60 min.

A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study.

PubMed

Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M; Kirk, Jeremy; Donaldson, Malcolm; Ivarsson, Sten-A; Söder, Olle; Roche, Edna; Hoey, Hilary; Dunger, David B; Juul, Anders

2014-10-01

Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies. In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration. The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, s.d. 0.019) and the low-dose group (35 μg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups. IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children. © 2014 European Society of Endocrinology.

Subject-driven titration of biphasic insulin aspart 30 twice daily is non-inferior to investigator-driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open-label, parallel-group, multicenter trial.

PubMed

Yang, Wenying; Zhu, Lvyun; Meng, Bangzhu; Liu, Yu; Wang, Wenhui; Ye, Shandong; Sun, Li; Miao, Heng; Guo, Lian; Wang, Zhanjian; Lv, Xiaofeng; Li, Quanmin; Ji, Qiuhe; Zhao, Weigang; Yang, Gangyi

2016-01-01

The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID). In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group. Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject-driven and investigator-driven groups, respectively. Subject-titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.

Sleep Quality, Short-Term and Long-Term CPAP Adherence

PubMed Central

Somiah, Manya; Taxin, Zachary; Keating, Joseph; Mooney, Anne M.; Norman, Robert G.; Rapoport, David M.; Ayappa, Indu

2012-01-01

Study Objectives: Adherence to CPAP therapy is low in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). The purpose of the present study was to evaluate the utility of measures of sleep architecture and sleep continuity on the CPAP titration study as predictors of both short- and long-term CPAP adherence. Methods: 93 patients with OSAHS (RDI 42.8 ± 34.3/h) underwent in-laboratory diagnostic polysomnography, CPAP titration, and follow-up polysomnography (NPSG) on CPAP. Adherence to CPAP was objectively monitored. Short-term (ST) CPAP adherence was averaged over 14 days immediately following the titration study. Long-term (LT) CPAP adherence was obtained in 56/93 patients after approximately 2 months of CPAP use. Patients were grouped into CPAP adherence groups for ST (< 2 h, 2-4 h, and > 4 h) and LT adherence (< 4 h, > 4 h). Sleep architecture, sleep disordered breathing (SDB) indices, and daytime outcome variables from the diagnostic and titration NPSGs were compared between CPAP adherence groups. Results: There was a significant relationship between ST and LT CPAP adherence (r = 0.81, p < 0.001). Neither ST nor LT adherence were related to demographic variables, baseline severity of untreated SDB, sleep architecture, or measures of daytime impairment. Good CPAP adherence groups had significantly lower %N2 and greater %REM on the titration NPSG. A model combining change in sleep efficiency and change in sleep continuity between the diagnostic and titration NPSGs predicted 17% of the variance in LT adherence (p = 0.006). Conclusions: These findings demonstrate that characteristics of sleep architecture, even on the titration NPSG, may predict some of the variance in CPAP adherence. Better sleep quality on the titration night was related to better CPAP adherence, suggesting that interventions to improve sleep on/prior to the CPAP titration study might be used as a therapeutic intervention to improve CPAP adherence. Citation: Somiah M; Taxin Z; Keating J; Mooney AM; Norman RG; Rapoport DM; Ayappa I. Sleep quality, short-term and long-term CPAP adherence. J Clin Sleep Med 2012;8(5):489-500. PMID:23066359

Structure and DNA-binding of meiosis-specific protein Hop2

NASA Astrophysics Data System (ADS)

Zhou, Donghua; Moktan, Hem; Pezza, Roberto

2014-03-01

Here we report structure elucidation of the DNA binding domain of homologous pairing protein 2 (Hop2), which is important to gene diversity when sperms and eggs are produced. Together with another protein Mnd1, Hop2 enhances the strand invasion activity of recombinase Dmc1 by over 30 times, facilitating proper synapsis of homologous chromosomes. However, the structural and biochemical bases for the function of Hop2 and Mnd1 have not been well understood. As a first step toward such understanding, we recently solved the structure for the N-terminus of Hop2 (1-84) using solution NMR. This fragment shows a typical winged-head conformation with recognized DNA binding activity. DNA interacting sites were then investigated by chemical shift perturbations in a titration experiment. Information of these sites was used to guide protein-DNA docking with MD simulation, revealing that helix 3 is stably lodged in the DNA major groove and that wing 1 (connecting strands 2 and 3) transiently comes in contact with the minor groove in nanosecond time scale. Mutagenesis analysis further confirmed the DNA binding sites in this fragment of the protein.

Interactions between antimicrobial polynorbornenes and phospholipid vesicles monitored by light scattering and microcalorimetry.

PubMed

Gabriel, Gregory J; Pool, Joanna G; Som, Abhigyan; Dabkowski, Jeffrey M; Coughlin, E Bryan; Muthukumar, M; Tew, Gregory N

2008-11-04

Antimicrobial polynorbornenes composed of facially amphiphilic monomers have been previously reported to accurately emulate the antimicrobial activity of natural host-defense peptides (HDPs). The lethal mechanism of most HDPs involves binding to the membrane surface of bacteria leading to compromised phospholipid bilayers. In this paper, the interactions between biomimetic vesicle membranes and these cationic antimicrobial polynorbornenes are reported. Vesicle dye-leakage experiments were consistent with previous biological assays and corroborated a mode of action involving membrane disruption. Dynamic light scattering (DLS) showed that these antimicrobial polymers cause extensive aggregation of vesicles without complete bilayer disintegration as observed with surfactants that efficiently solubilize the membrane. Fluorescence microscopy on vesicles and bacterial cells also showed polymer-induced aggregation of both synthetic vesicles and bacterial cells. Isothermal titration calorimetry (ITC) afforded free energy of binding values (Delta G) and polymer to lipid binding ratios, plus revealed that the interaction is entropically favorable (Delta S>0, Delta H>0). It was observed that the strength of vesicle binding was similar between the active polymers while the binding stoichiometries were dramatically different.

A quantitative speciation model for the adsorption of organic pollutants on activated carbon.

PubMed

Grivé, M; García, D; Domènech, C; Richard, L; Rojo, I; Martínez, X; Rovira, M

2013-01-01

Granular activated carbon (GAC) is commonly used as adsorbent in water treatment plants given its high capacity for retaining organic pollutants in aqueous phase. The current knowledge on GAC behaviour is essentially empirical, and no quantitative description of the chemical relationships between GAC surface groups and pollutants has been proposed. In this paper, we describe a quantitative model for the adsorption of atrazine onto GAC surface. The model is based on results of potentiometric titrations and three types of adsorption experiments which have been carried out in order to determine the nature and distribution of the functional groups on the GAC surface, and evaluate the adsorption characteristics of GAC towards atrazine. Potentiometric titrations have indicated the existence of at least two different families of chemical groups on the GAC surface, including phenolic- and benzoic-type surface groups. Adsorption experiments with atrazine have been satisfactorily modelled with the geochemical code PhreeqC, assuming that atrazine is sorbed onto the GAC surface in equilibrium (log Ks = 5.1 ± 0.5). Independent thermodynamic calculations suggest a possible adsorption of atrazine on a benzoic derivative. The present work opens a new approach for improving the adsorption capabilities of GAC towards organic pollutants by modifying its chemical properties.

Electrophoretic separation of alginic sodium diester and sodium hexametaphosphate in chondroitin sulfate that interfere with the cetylpyridinium chloride titration assay.

PubMed

Weiguo, Zhang; Giancaspro, Gabriel; Adams, Kristie M; Neal-Kababick, James; Hildreth, Jana; Li, Aishan; Roman, Mark C; Betz, Joseph M

2014-01-01

The most commonly used chondroitin sulfate (CS) assay method is cetylpyridinium chloride (CPC) titration. Cellulose acetate membrane electrophoresis (CAME) is the technique used for detection of impurities in the U.S. Pharmacopeia's CS monograph. Because CPC titration is a relatively nonspecific quantitative technique, the apparent amount of CS as determined by CPC titration alone may not reflect the true amount of CS due to possible interference with the CPC assay by impurities that contain CPC titratable functional groups. When CAME is used in conjunction with CPC titration, certain non-CS and adulterants can be visualized and estimated, and a true value for CS can be assigned once the presence of these non-CS impurities has been ruled out. This study examines conjunct application of CPC and CAME in ascertaining CS assay and purity in the presence of certain adulterants. These include propylene glycol alginate sulfate sodium, known in commerce as alginic sodium diester (ASD), and Zero One (Z1), a water-soluble agent newly reported in the CS marketplace and subsequently identified as sodium hexametaphosphate. ASD, Z1, and CS are similar in physical appearance and solubility in water and ethanol. They are also titratable anions and form ionic pairs with CPC, therefore interfering with the CPC titration assay for CS CAME separates these adulterants from each other and from CS by differences in their electrophoretic mobility. CAME is able to detect these impurities in CS at levels as low as 0.66% by weight. Although it is recommended that a method for detecting impurities (e.g., CAME) be used in cormbination with relatively nonspecific assay methods such as CPC titration, this is seldom done in practice. Assay results for CS derived fromn CPC titration may, therefore, be misleading, leaving the CS supply chain vulnerable to adulteration. In this study, the authors investigated ASD and Z1 adulteration of CS and developed an electrophoretic separation of these adulterants in CS and procedures to isolate ASD from CS matrixes containing these adulterants. The authors describe in this paper utilization of an orthogonal approach to establish the identity of Z1 as sodium hexametaphosphate and to confirm the identity of ASD, including ethanol fractionation, FTIR spectroscopy, differential scanning calorimetry, and NMR spectroscopy. The authors suggest that CAME is a cost-effective and easy to use methodfor detecting certain impurities in CS raw ingredients and recommend that CPC and CAME be used in combination by QC laboratories as a means of effectively deterring the practice of adulterating CS raw materials with the known adulterants ASD and Z1 and/or other non-chondroitin substances that can be separated from CSby CAME and that exhibit CPC titration behavior similar to CS.

Combination of a Copper-Ion Selective Electrode and Fluorometric Titration for the Determination of Copper(II) Ion Conditional Stability Constants of Humic Substances.

PubMed

Chen, Juan; Chen, Hao; Zhang, Xing-wen; Lei, Kun; Kenny, Jonathan E

2015-11-01

A fluorescence quenching model using copper(II) ion (Cu(2+)) ion selective electrode (Cu-ISE) is developed. It uses parallel factor analysis (PARAFAC) to model fluorescence excitation-emission matrices (EEMs) of humic acid (HA) samples titrated with Cu(2+) to resolve fluorescence response of fluorescent components to Cu(2+) titration. Meanwhile, Cu-ISE is employed to monitor free Cu(2+) concentration ([Cu]) at each titration step. The fluorescence response of each component is fit individually to a nonlinear function of [Cu] to find the Cu(2+) conditional stability constant for that component. This approach differs from other fluorescence quenching models, including the most up-to-date multi-response model that has a problematic assumption on Cu(2+) speciation, i.e., an assumption that total Cu(2+) present in samples is a sum of [Cu] and those bound by fluorescent components without taking into consideration the contribution of non-fluorescent organic ligands and inorganic ligands to speciation of Cu(2+). This paper employs the new approach to investigate Cu(2+) binding by Pahokee peat HA (PPHA) at pH values of 6.0, 7.0, and 8.0 buffered by phosphate or without buffer. Two fluorescent components (C1 and C2) were identified by PARAFAC. For the new quenching model, the conditional stability constants (logK1 and logK2) of the two components all increased with increasing pH. In buffered solutions, the new quenching model reported logK1 = 7.11, 7.89, 8.04 for C1 and logK2 = 7.04, 7.64, 8.11 for C2 at pH 6.0, 7.0, and 8.0, respectively, nearly two log units higher than the results of the multi-response model. Without buffer, logK1 and logK2 decreased but were still high (>7) at pH 8.0 (logK1 = 7.54, logK2 = 7.95), and all the values were at least 0.5 log unit higher than those (4.83 ~ 5.55) of the multi-response model. These observations indicate that the new quenching model is more intrinsically sensitive than the multi-response model in revealing strong fluorescent binding sites of PPHA in different experimental conditions. The new model was validated by testing it with a mixture of two fluorescing Cu(2+) chelating organic compounds, i.e., l-tryptophan and salicylic acid mixed with one non-fluorescent binding compound oxalic acid titrated with Cu(2+) at pH 5.0.

Hydrous ferric oxide: evaluation of Cd-HFO surface complexation models combining Cd(K) EXAFS data, potentiometric titration results, and surface site structures identified from mineralogical knowledge.

PubMed

Spadini, Lorenzo; Schindler, Paul W; Charlet, Laurent; Manceau, Alain; Vala Ragnarsdottir, K

2003-10-01

The surface properties of ferrihydrite were studied by combining wet chemical data, Cd(K) EXAFS data, and a surface structure and protonation model of the ferrihydrite surface. Acid-base titration experiments and Cd(II)-ferrihydrite sorption experiments were performed within 3<-log[H(+)]<10.5 and 0.5<[Cd(t)]<12 mM in 0.3 M NaClO(4) at 25 degrees C, where [Cd(t)] refers to total Cd concentration. Measurements at -5.5triple bond Fe-OH(-1/2),logk((int))=-8.29, assuming the existence of a unique intrinsic microscopic constant, logk((int)), and consequently the existence of a single significant type of acid-base reactive functional groups. The surface structure model indicates that these groups are terminal water groups. The Cd(II) data were modeled assuming the existence of a single reactive site. The model fits the data set at low Cd(II) concentration and up to 50% surface coverage. At high coverage more Cd(II) ions than predicted are adsorbed, which is indicative of the existence of a second type of site of lower affinity. This agrees with the surface structure and protonation model developed, which indicates comparable concentrations of high- and low-affinity sites. The model further shows that for each class of low- and high-affinity sites there exists a variety of corresponding Cd surface complex structure, depending on the model crystal faces on which the complexes develop. Generally, high-affinity surface structures have surface coordinations of 3 and 4, as compared to 1 and 2 for low-affinity surface structures.

Analysis of titanium content in titanium tetrachloride solution

NASA Astrophysics Data System (ADS)

Bi, Xiaoguo; Dong, Yingnan; Li, Shanshan; Guan, Duojiao; Wang, Jianyu; Tang, Meiling

2018-03-01

Strontium titanate, barium titan and lead titanate are new type of functional ceramic materials with good prospect, and titanium tetrachloride is a commonly in the production such products. Which excellent electrochemical performance of ferroelectric tempreature coefficient effect.In this article, three methods are used to calibrate the samples of titanium tetrachloride solution by back titration method, replacement titration method and gravimetric analysis method. The results show that the back titration method has many good points, for example, relatively simple operation, easy to judgment the titration end point, better accuracy and precision of analytical results, the relative standard deviation not less than 0.2%. So, it is the ideal of conventional analysis methods in the mass production.

A highly selective and sensitive fluorescent chemosensor and its application for rapid on-site detection of Al3 +

NASA Astrophysics Data System (ADS)

Yue, Xiao-li; Wang, Zhao-qing; Li, Chao-rui; Yang, Zheng-yin

2018-03-01

In this paper, a simple naphthalene-based derivative (HL) has been designed and synthesized as a Al3 +-selective fluorescent chemosensor based on the PET mechanism. HL exhibited high selectivity and sensitivity towards Al3 + over other commonly coexisting metal ions in ethanol with a detection limit of 2.72 nM. The 1:1 binding stoichiometry of the complex (HL-Al3 +) was determined from the Job's plot based on fluorescence titrations and the ESI-MS spectrum data. Moreover, the binding site of HL with Al3 + was assured by the 1H NMR titration experiment. The binding constant (Ka) of the complex (HL-Al3 +) was calculated to be 5.06 × 104 M- 1 according to the Benesi-Hildebrand equation. In addition, the recognizing process of HL towards Al3 + was chemically reversible by adding Na2EDTA. Importantly, HL could directly and rapidly detect aluminum ion through the filter paper without resorting to additional instrumental analysis.

Mechanistic understanding of monosaccharide-air flow battery electrochemistry

NASA Astrophysics Data System (ADS)

Scott, Daniel M.; Tsang, Tsz Ho; Chetty, Leticia; Aloi, Sekotilani; Liaw, Bor Yann

Recently, an inexpensive monosaccharide-air flow battery configuration has been demonstrated to utilize a strong base and a mediator redox dye to harness electrical power from the partial oxidation of glucose. Here the mechanistic understanding of glucose oxidation in this unique glucose-air power source is further explored by acid-base titration experiments, 13C NMR, and comparison of results from chemically different redox mediators (indigo carmine vs. methyl viologen) and sugars (fructose vs. glucose) via studies using electrochemical techniques. Titration results indicate that gluconic acid is the main product of the cell reaction, as supported by evidence in the 13C NMR spectra. Using indigo carmine as the mediator dye and fructose as the energy source, an abiotic cell configuration generates a power density of 1.66 mW cm -2, which is greater than that produced from glucose under similar conditions (ca. 1.28 mW cm -2). A faster transition from fructose into the ene-diol intermediate than from glucose likely contributed to this difference in power density.

Development of self and peer performance assessment on iodometric titration experiment

NASA Astrophysics Data System (ADS)

Nahadi; Siswaningsih, W.; Kusumaningtyas, H.

2018-05-01

This study aims to describe the process in developing of reliable and valid assessment to measure students’ performance on iodometric titration and the effect of the self and peer assessment on students’ performance. The self and peer-instrument provides valuable feedback for the student performance improvement. The developed assessment contains rubric and task for facilitating self and peer assessment. The participants are 24 students at the second-grade student in certain vocational high school in Bandung. The participants divided into two groups. The first 12 students involved in the validity test of the developed assessment, while the remain 12 students participated for the reliability test. The content validity was evaluated based on the judgment experts. Test result of content validity based on judgment expert show that the developed performance assessment instrument categorized as valid on each task with the realibity classified as very good. Analysis of the impact of the self and peer assessment implementation showed that the peer instrument supported the self assessment.

Correct titration of non-drugs and some other methodological issues.

PubMed

Beneke, M; Rasmus, W; Rød, I S; Fritze, J

1994-01-01

Doctors' prescription and dosing behaviour was investigated using data from 9 clinical trials in 550 patients treated with psychotropics. 7 trials were conducted under double- and 2 under single-blind conditions. In 3 of these trials, oral and i.m. preparations were used demanding a double-dummy design. All patients were evaluated on a weekly or 2-week basis using psychopathological rating scales (i.e. Hamilton Anxiety Scale, Hamilton Depression Scale, Clinical Global Impressions, Simpson and Angus EPS). It was found that (a) oral-medication titration was 3- to 4-fold more broad-ranging than i.m. medication titration, (b) oral placebo was titrated to the same extent as the oral investigational drugs, and (c) the titration schedule did not follow protocol requirements. Moreover, the average doses in all drug and placebo groups were the same. Concomitant medication like sleep inducers was found to be more closely related to doctors' habits than to actual medical need. Independent of trial and investigational drug, 10-33% of all patients received additional sleep inducers.

An Ion-Selective Electrode for the Determination of Phencyclidine (PCP).

DTIC Science & Technology

1980-08-06

as an indicator_ ectrode in potentiometric titration of PCPA at concentrations DD 1473 EDITION or I Nov soIS OSSOOL TC SEPURqITY CLAWSFICATION Of...and ISE detection limits determined as described previous (25). The PCP electrode was used as the indicator electrode in potentiometric titrations of...was standardized by potentiometric titration with a dodecyltrimethyl- ammonium bromide (DoTAB) solution using a DoTA+ ISE (25) as the indicator

[Not Available].

PubMed

Burgot, J L

1978-04-01

Maleic, fumaric, tartaric, glutaric and adipic acids are titrated directly with sodium hydroxide by means of an automatic thermometric titrimeter. The titration curves have two break-points, corresponding to the successive neutralization of the two acid groups. Previous standardization permits measurement of the heats of neutralization, from which the enthalpies of dissociation can be deduced. From 0.3 to 1 mmole of acid can be titrated with a relative standard deviation of about 3%.

Use of vitreous carbon as a working electrode in coulometric titration of potassium hydrogen phthalate.

PubMed

Jennings, V J; Dodson, A; Tedds, G

1973-07-01

The use of a vitreous carbon electrode as a cathode in the amperostatic coulometric titration of aqueous potassium hydrogen phthalate solution is described. It is shown that 10 mg of the phthalate can be titrated with a precision better than 0.5%. Current-voltage curves for platinum and vitreous carbon cathodes show that there is an overpotential on the latter relative to the former.

Reduction and determination of dixanthogens.

PubMed

Prasad, M S

1971-06-01

A convenient method for the reduction and determination of dixaathogen has been developed. It is based on the quantitative reaction of dixanthogen with zinc amalgam to form xanthate; the latter can be determined by iodine titration, potentiometric titration with silver nitrate or by spectrophotometry at 310 mmu. Dixanthogen can be determined in mixtures containing xanthate, by titration of aliquots with and without reduction. Higher dixanthogens can also be determined, and flotation liquors analysed.

Comparison of a gel microcolumn assay with the conventional tube test for red blood cell alloantibody titration.

PubMed

Finck, Rachel; Lui-Deguzman, Carrie; Teng, Shih-Mao; Davis, Rebecca; Yuan, Shan

2013-04-01

Titration is a semiquantitative method used to estimate red blood cell (RBC) alloantibody reactivity. The conventional tube test (CTT) technique is the traditional method for performing titration studies. The gel microcolumn assay (GMA) is also a sensitive method to detect RBC alloantibodies. The aim of this study was to compare a GMA with the CTT technique in the performance of Rh and K alloantibody titration. Patient serum samples that contained an RBC alloantibody with a singular specificity were identified by routine blood bank workflow. Parallel titration studies were performed on these samples by both the CTT method and a GMA (ID-Micro Typing System anti-IgG gel card, Micro Typing Systems, Inc., an Ortho-Clinical Diagnostics Company). Forty-eight samples were included, including 11 anti-D, five anti-c, 13 anti-E, one anti-C, three anti-e, and 15 anti-K. Overall, the two methods generated identical results in 21 of 48 samples. For 42 samples (87.5%) the two methods generated results that were within one serial dilution, and for the remaining six samples, results were within two dilutions. GMA systems may perform comparably to the CTT in titrating alloantibodies to Rh and Kell antigens. © 2012 American Association of Blood Banks.

Probing the Energetics of Antigen-Antibody Recognition by Titration Microcalorimetry

PubMed

Jelesarov; Leder; Bosshard

1996-06-01

Our understanding of the energetics that govern antigen-antibody recognition lags behind the increasingly rapid accumulation of structural information on antigen-antibody complexes. Thanks to the development of highly sensitive microcalorimeters, the thermodynamic parameters of antigen-antibody interactions can now be measured with precision and using only nanomole quantities of protein. The method of choice is isothermal titration calorimetry, in which a solution of the antibody (or antigen) is titrated with small aliquots of the antigen (or antibody) and the heat change accompanying the formation of the antigen-antibody complex is measured with a sensitivity as high as 0.1 μcal s-1. The free energy of binding (DeltaG), the binding enthalpy (DeltaH), and the binding entropy (DeltaS) are usually obtained from a single experiment, and no spectroscopic or radioactive label must be introduced into the antigen or antibody. The often large and negative change in heat capacity (DeltaCp) accompanying the formation of an antigen-antibody complex is obtained from DeltaH measured at different temperatures. The basic theory and the principle of the measurements are reviewed and illustrated by examples. The thermodynamic parameters relate to the dynamic physical forces that govern the association of the freely moving antigen and antibody into a well-structured and unique complex. This information complements the static picture of the antigen-antibody complex that results from X-ray diffraction analysis. Attempts to correlate dynamic and static aspects are discussed briefly.

Identification of functional groups of Opuntia ficus-indica involved in coagulation process after its active part extraction.

PubMed

Bouaouine, Omar; Bourven, Isabelle; Khalil, Fouad; Baudu, Michel

2018-04-01

Opuntia ficus-indica that belongs to the Cactaceae family and is a member of Opuntia kind has received increasing research interest for wastewater treatment by flocculation. The objectives of this study were (i) to provide more information regarding the active constituents of Opuntia spp. and (ii) to improve the extracting and using conditions of the flocculant molecules for water treatment. A classic approach by jar test experiments was used with raw and extracted material by solubilization and precipitation. The surface properties of solid material were characterized by FTIR, SEM, zeta potential measurement, and surface titration. The splitting based on the solubility of the material with pH and the titration of functional groups completed the method. The optimal pH value for a coagulation-flocculation process using cactus solid material (CSM) was 10.0 and a processing rate of 35 mg L -1 . The alkaline pH of flocculation suggests an adsorption mechanism with bridging effect between particles by water-soluble extracted molecules. To validate this mechanism, an extraction water was carried out at pH = 10 (optimum of flocculation) and the solution was acidified (pH = 7) to allow precipitation of so considered active flocculant molecules. The strong flocculant property of this extract was verified, and titration of this solution showed at least one specific pKa of 9.0 ± 0.6. This pKa corresponds to phenol groups, which could be assigned to lignin and tannin.

Italian external quality assessment program for cystic fibrosis sweat chloride test: a 2015 and 2016 results comparison.

PubMed

Salvatore, Marco; Floridia, Giovanna; Amato, Annalisa; Censi, Federica; de Stefano, Maria Chiara; Ferrari, Gianluca; Tosto, Fabrizio; Taruscio, Domenica

2017-01-01

Diagnostic testing in cystic fibrosis (CF) is based on the sweat chloride test (SCT) in the context of appropriate signs and symptoms of disease and results of the gene mutation analysis. In 2014 the Istituto Superiore di Sanità (ISS) established a pilot Italian external quality assessment program for CF sweat chloride test (Italian EQA-SCT). In 2015 this activity was recognized as a third party service carried out by the ISS. The aim of the paper is to compare 2015 and 2016 results and experiences. The scheme is prospective; enrollment is voluntary and the payment of a fee is required. Participants are registered and identified by a specific Identification Number (ID) through a dedicated web-facility. Assessment covers analysis, interpretation and reporting of results. Thirteen and fifteen laboratories, participated in the 2015 and 2016 round respectively. Seven laboratories participated constantly from 2014, eleven participated both in 2015 and 2016 and four participated in 2016 for the first time. Variability in scores of chloride titration and heterogeneity in interpretation/reporting results were detected in both rounds. A total of 18 critical errors in chloride titration were made by eight different participants. Four laboratories made errors in chloride titration in 2015 but drastically improved their performance in 2016. In 2016 poor performance criteria were established and adopted. Even though results show variability in performance of laboratories, constant and mandatory participation may contribute to the improvement of performance and quality reached by laboratory.

Sinorhizobium meliloti chemotaxis to quaternary ammonium compounds is mediated by the chemoreceptor McpX.

PubMed

Webb, Benjamin A; Karl Compton, K; Castañeda Saldaña, Rafael; Arapov, Timofey D; Keith Ray, W; Helm, Richard F; Scharf, Birgit E

2017-01-01

The bacterium Sinorhizobium meliloti is attracted to seed exudates of its host plant alfalfa (Medicago sativa). Since quaternary ammonium compounds (QACs) are exuded by germinating seeds, we assayed chemotaxis of S. meliloti towards betonicine, choline, glycine betaine, stachydrine and trigonelline. The wild type displayed a positive response to all QACs. Using LC-MS, we determined that each germinating alfalfa seed exuded QACs in the nanogram range. Compared to the closely related nonhost species, spotted medic (Medicago arabica), unique profiles were released. Further assessments of single chemoreceptor deletion strains revealed that an mcpX deletion strain displayed little to no response to these compounds. Differential scanning fluorimetry showed interaction of the isolated periplasmic region of McpX (McpX PR and McpX 34-306 ) with QACs. Isothermal titration calorimetry experiments revealed tight binding to McpX PR with dissociation constants (K d ) in the nanomolar range for choline and glycine betaine, micromolar K d for stachydrine and trigonelline and a K d in the millimolar range for betonicine. Our discovery of S. meliloti chemotaxis to plant-derived QACs adds another role to this group of compounds, which are known to serve as nutrient sources, osmoprotectants and cell-to-cell signalling molecules. This is the first report of a chemoreceptor that mediates QACs taxis through direct binding. © 2016 John Wiley & Sons Ltd.

(Non) formation of methanol by direct hydrogenation of formate on copper catalysts

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

Yang, Yong; Mims, Charles A.; Disselkamp, Robert S.

2010-10-14

We have attempted to hydrogenate adsorbed formate species on copper catalysts to probe the importance of this postulated mechanistic step in methanol synthesis. Surface formate coverages up to 0.25 were produced at temperatures between 413K and 453K on supported (Cu/SiO2) copper and unsupported copper catalysts. The adlayers were produced by various methods including (1) steady state catalytic conditions in CO2-H2 (3:1, 6 bar) atmospheres, and (2) by exposure of the catalysts to formic acid. As reported in earlier work, the catalytic surface at steady state contains bidentate formate species with coverages up to saturation levels of ~ 0.25 at themore » low temperatures of this study. The reactivity of these formate adlayers was investigated at relevant reaction temperatures in atmospheres containing up to 6 bar H2 partial pressure by simultaneous mass spectrometry (MS) and infrared (IR) spectroscopy measurements. The yield of methanol during the attempted hydrogenation (“titration”) of these adlayers was insignificant (<0.2 mol % of the formate adlayer) even in dry hydrogen partial pressures up to 6 bar. Hydrogen titration of formate species produced from formic acid also failed to produce significant quantities of methanol, and attempted titration in gases consisting of CO-hydrogen mixtures or dry CO2 were also unproductive. The formate decomposition kinetics, measured by IR, were also unaffected by these changes in the gas composition. Similar experiments on unsupported copper also failed to show any methanol. From these results, we conclude that methanol synthesis on copper cannot result from the direct hydrogenation of (bidentate) formate species in simple steps involving adsorbed H species alone. Furthermore, experiments performed on both supported (Cu/SiO2) and unsupported copper catalysts gave similar results implying that the methanol synthesis reaction mechanism only involves metal surface chemistry. Pre-exposure of the bidentate formate adlayer to oxidation by O2 or N2O produces a change to a monodentate configuration. Attempted titration of this monodentate formate/O coadsorbed layer in dry hydrogen produces significant quantities of methanol, although decomposition of formate to carbon dioxide and hydrogen remains the dominant reaction pathway. Simultaneous production of water is also observed during this titration as the copper surface is re-reduced. These results indicate that co-adsorbates related to surface oxygen or water-derived species may be critical to methanol production on copper, perhaps assisting in the hydrogenation of adsorbed formate to adsorbed methoxyl.« less

Chemistry of manganese precipitation in Pinal Creek, Arizona, USA: A laboratory study

USGS Publications Warehouse

Hem, J.D.; Lind, Carol J.

1994-01-01

Groundwater underlying the valley of Pinal Creek downstream from Globe, Arizona, has been contaminated by low-pH metal-enriched wastewater from copper mining and ore processing at Miami, Arizona. At present, the acidity and most of the dissolved metal content, except for Mn, of the wastewater is removed by reactions with carbonate and other solids in the alluvial aquifer before the neutralized contaminated water enters the creek channel and becomes surface flow. Where flow in the creek is perennial, Mn-bearing precipitates are formed in the stream bed and in some places in the subsurface. As an aid to understanding the processes involved and explaining the mineralogy of the precipitates, closely controlled laboratory redox titration experiments were performed on samples of surface flow and groundwater taken near the head of perennial flow in the creek. The high content of dissolved Ca, Mg, Mn and COP2 species in the neutralized contaminated groundwater caused precipitation of some of the Mn as kutnahorite, (Mn, Mg)Ca(CO3)2, when the experimental system was held between pH 8.5 and 9.0 while CO2-free air was bubbled into the solution. Hausmannite and manganite also were precipitated, in somewhat lower amounts. When the concentrations of dissolved CO2 species in the groundwater sample were decreased before the experiment was started, the Mn precipitated was predominantly in the oxides hausmannite and manganite. In some of the experimental titrations clinoenstatite, (MgSiO3), was precipitated. After titrations were stopped the solutions and precipitates were allowed to stand, with limited access to the atmosphere, for several months. During this aging period the degree of oxidation of the precipitated Mn increased and in one precipitate from an experimental solution the Ca + Mn4+ oxides todorokite and takanelite were identified. These oxides also have been identified in streambed precipitates. Some of these precipitates also gave X-ray diffraction reflections for kutnahorite. Thermodynamic feasibilities of eight potential chemical reactions forming solid phases of interest were evaluated by calculating their respective reaction affinities attained during titration and aging. The results are in general agreement with the indications for the presence of these species given by X-ray and electron diffraction. The presence of carbonates in precipitated encrustations formed from groundwater below the land surface and their occurrence in manganese oxide crusts that precipitate from the creek water, also are predicted by these results. ?? 1994.

Mesoporous Carbons With Self-Assembled High-Activity Surfaces (PREPRINT)

DTIC Science & Technology

2006-07-07

temperature-programmed desorption, and potentiometric titrations . Journal of Colloid and Interface Science 2001; 240: 252–258. [40] Rotkin SV, Gogotsi Y...selected carbon samples were treated with nitric acid and the total acid site density determined by base titration [32-34 Boehm 1994; Boehm 2002; 32...washed thoroughly using distilled/deionized water, and dried in the oven. For the titration , 50 mg of HNO3-treated carbon powder was added to 20 ml

High-Molecular Compounds (Selected Articles).

DTIC Science & Technology

1987-10-15

us ions The method of potentiometric titration in dimethylformamide was used to study the structure of macro molecular chain of copolymers based on...macromolecular chain we used the method of potential metric titration . The objects of the study uere alpha chloroacrylic acid (KO)K) in monomer...homopolymer, and copolymer (with methylmethacrylate) form 131. I e d* r. I%0 I 0 12 # z Curves of potential metric titration of solutions of copolymers of KjAK

The Thermodynamics of the Carbonate System in Seawater,

DTIC Science & Technology

1979-03-08

ionization of water at various water by potentiometric titration . Deep-Sea Res. 17, temperatures from molal volume data. J. Soln. Chem. 737-750. 1... titration alkalinity, AT, givcn by not available at low salinities and molal volume cal- A, = [HCO/] + 2[CO2-] + [B(OH-] culations (MILLERO et al...used to characterize obtained by a computer titration improves, pH the parameters of the carbonate system in seawater. measurements should be made. This

The Velocity of Sound in Sea Water at Zero Depth

DTIC Science & Technology

1952-06-11

the Woods Hole Oceanographic Institution. Toward the end of this investigation a potentiometric titration with the Beckman automatic titratcr and a...Interferon eter as soon as received, and at Intervals throughout the investigation. Ch!orlnitie3 were determined by the Mohr method of AgNOi titration ...chlorinity of each of the solutions was actually determined by Mohr titration in the sar.? manner as the chiorinities of the original samples. The

Process for Assessing the Stability of HAN (Hydroxylammonium Nitrate)-Based Liquid Propellants

DTIC Science & Technology

1989-02-09

Scholz, Guidelines by Messrs. Riedel - de Haen for Titration according to the Karl Fischer Method ), 3. Auflage/3rd Edition 1982 /22/ JANDER; G. and... Potentiometric determination of the equivalence point is the most suitable method /15/. Time is saved by using automatically recording titration 33...propellant. The water content of liquid propellants on the basis of HAN according to Fig. 6 can be determined directly by Karl Fischer titration. This

Molecular interaction of 2,4-diacetylphloroglucinol (DAPG) with human serum albumin (HSA): The spectroscopic, calorimetric and computational investigation

NASA Astrophysics Data System (ADS)

Pragna Lakshmi, T.; Mondal, Moumita; Ramadas, Krishna; Natarajan, Sakthivel

2017-08-01

Drug molecule interaction with human serum albumin (HSA) affects the distribution and elimination of the drug. The compound, 2,4-diacetylphloroglucinol (DAPG) has been known for its antimicrobial, antiviral, antihelminthic and anticancer properties. However, its interaction with HSA is not yet reported. In this study, the interaction between HSA and DAPG was investigated through steady-state fluorescence, time-resolved fluorescence (TRF), circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy, isothermal titration calorimetry (ITC), molecular docking and molecular dynamics simulation (MDS). Fluorescence spectroscopy results showed the strong quenching of intrinsic fluorescence of HSA due to interaction with DAPG, through dynamic quenching mechanism. The compound bound to HSA with reversible and moderate affinity which explained its easy diffusion from circulatory system to target tissue. The thermodynamic parameters from fluorescence spectroscopic data clearly revealed the contribution of hydrophobic forces but, the role of hydrogen bonds was not negligible according to the ITC studies. The interaction was exothermic and spontaneous in nature. Binding with DAPG reduced the helical content of protein suggesting the unfolding of HSA. Site marker fluorescence experiments revealed the change in binding constant of DAPG in the presence of site I (warfarin) but not site II marker (ibuprofen) which confirmed that the DAPG bound to site I. ITC experiments also supported this as site I marker could not bind to HSA-DAPG complex while site II marker was accommodated in the complex. In silico studies further showed the lowest binding affinity and more stability of DAPG in site I than in site II. Thus the data presented in this study confirms the binding of DAPG to the site I of HSA which may help in further understanding of pharmacokinetic properties of DAPG.

Supramolecular interaction of 6-shogaol, a therapeutic agent of Zingiber officinale with human serum albumin as elucidated by spectroscopic, calorimetric and molecular docking methods.

PubMed

Feroz, S R; Mohamad, S B; Lee, G S; Malek, S N A; Tayyab, S

2015-06-01

6-Shogaol, one of the main bioactive constituents of Zingiber officinale has been shown to possess various therapeutic properties. Interaction of a therapeutic compound with plasma proteins greatly affects its pharmacokinetic and pharmacodynamic properties. The present investigation was undertaken to characterize the interaction between 6-shogaol and the main in vivo transporter, human serum albumin (HSA). Various binding characteristics of 6-shogaol-HSA interaction were studied using fluorescence spectroscopy. Thermal stability of 6-shogaol-HSA system was determined by circular dichroism (CD) and differential scanning calorimetric (DSC) techniques. Identification of the 6-shogaol binding site on HSA was made by competitive drug displacement and molecular docking experiments. Fluorescence quench titration results revealed the association constant, Ka of 6-shogaol-HSA interaction as 6.29 ± 0.33 × 10(4) M(-1) at 25 ºC. Values of the enthalpy change (-11.76 kJ mol(-1)) and the entropy change (52.52 J mol(-1) K(-1)), obtained for the binding reaction suggested involvement of hydrophobic and van der Waals forces along with hydrogen bonds in the complex formation. Higher thermal stability of HSA was noticed in the presence of 6-shogaol, as revealed by DSC and thermal denaturation profiles. Competitive ligand displacement experiments along with molecular docking results suggested the binding preference of 6-shogaol for Sudlow's site I of HSA. All these results suggest that 6-shogaol binds to Sudlow's site I of HSA through moderate binding affinity and involves hydrophobic and van der Waals forces along with hydrogen bonds. Copyright © 2015 Elsevier GmbH. All rights reserved.

The crystal structure of the AgamOBP1•Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition.

PubMed

Drakou, Christina E; Tsitsanou, Katerina E; Potamitis, Constantinos; Fessas, Dimitrios; Zervou, Maria; Zographos, Spyros E

2017-01-01

Anopheles gambiae Odorant Binding Protein 1 in complex with the most widely used insect repellent DEET, was the first reported crystal structure of an olfactory macromolecule with a repellent, and paved the way for OBP1-structure-based approaches for discovery of new host-seeking disruptors. In this work, we performed STD-NMR experiments to directly monitor and verify the formation of a complex between AgamOBP1 and Icaridin, an efficient DEET alternative. Furthermore, Isothermal Titration Calorimetry experiments provided evidence for two Icaridin-binding sites with different affinities (Kd = 0.034 and 0.714 mM) and thermodynamic profiles of ligand binding. To elucidate the binding mode of Icaridin, the crystal structure of AgamOBP1•Icaridin complex was determined at 1.75 Å resolution. We found that Icaridin binds to the DEET-binding site in two distinct orientations and also to a novel binding site located at the C-terminal region. Importantly, only the most active 1R,2S-isomer of Icaridin's equimolar diastereoisomeric mixture binds to the AgamOBP1 crystal, providing structural evidence for the possible contribution of OBP1 to the stereoselectivity of Icaridin perception in mosquitoes. Structural analysis revealed two ensembles of conformations differing mainly in spatial arrangement of their sec-butyl moieties. Moreover, structural comparison with DEET indicates a common recognition mechanism for these structurally related repellents. Ligand interactions with both sites and binding modes were further confirmed by 2D 1 H- 15 N HSQC NMR spectroscopy. The identification of a novel repellent-binding site in AgamOBP1 and the observed structural conservation and stereoselectivity of its DEET/Icaridin-binding sites open new perspectives for the OBP1-structure-based discovery of next-generation insect repellents.

Nickel binding and [NiFe]-hydrogenase maturation by the metallochaperone SlyD with a single metal-binding site in Escherichia coli.

PubMed

Kaluarachchi, Harini; Altenstein, Matthias; Sugumar, Sonia R; Balbach, Jochen; Zamble, Deborah B; Haupt, Caroline

2012-03-16

SlyD (sensitive to lysis D) is a nickel metallochaperone involved in the maturation of [NiFe]-hydrogenases in Escherichia coli (E. coli) and specifically contributes to the nickel delivery step during enzyme biosynthesis. This protein contains a C-terminal metal-binding domain that is rich in potential metal-binding residues that enable SlyD to bind multiple nickel ions with high affinity. The SlyD homolog from Thermus thermophilus does not contain the extended cysteine- and histidine-rich C-terminal tail of the E. coli protein, yet it binds a single Ni(II) ion tightly. To investigate whether a single metal-binding motif can functionally replace the full-length domain, we generated a truncation of E. coli SlyD, SlyD155. Ni(II) binding to SlyD155 was investigated by using isothermal titration calorimetry, NMR and electrospray ionization mass spectrometry measurements. This in vitro characterization revealed that SlyD155 contains a single metal-binding motif with high affinity for nickel. Structural characterization by X-ray absorption spectroscopy and NMR indicated that nickel was coordinated in an octahedral geometry with at least two histidines as ligands. Heterodimerization between SlyD and another hydrogenase accessory protein, HypB, is essential for optimal hydrogenase maturation and was confirmed for SlyD155 via cross-linking experiments and NMR titrations, as were conserved chaperone and peptidyl-prolyl isomerase activities. Although these properties of SlyD are preserved in the truncated version, it does not modulate nickel binding to HypB in vitro or contribute to the maturation of [NiFe]-hydrogenases in vivo, unlike the full-length protein. This study highlights the importance of the unusual metal-binding domain of E. coli SlyD in hydrogenase biogenesis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Kinetic, Thermodynamic, and Structural Insight into the Mechanism of Phosphopantetheine Adenylyltransferase from Mycobacterium tuberculosis

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

Wubben, Thomas J.; Mesecar, Andrew D.; UIC)

Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4'-phosphopantetheine (PhP) to form dephosphocoenzyme A. This reaction sits at the branch point between the de novo pathway and the salvage pathway, and has been shown to be a rate-limiting step in the biosynthesis of CoA. Importantly, bacterial and mammalian PPATs share little sequence homology, making the enzyme a potential target for antibiotic development. A series of steady-state kinetic, product inhibition, and direct binding studies with Mycobacterium tuberculosis PPAT (MtPPAT) was conducted and suggests that the enzyme utilizesmore » a nonrapid-equilibrium random bi-bi mechanism. The kinetic response of MtPPAT to the binding of ATP was observed to be sigmoidal under fixed PhP concentrations, but substrate inhibition was observed at high PhP concentrations under subsaturating ATP concentrations, suggesting a preferred pathway to ternary complex formation. Negative cooperativity in the kinetic response of MtPPAT to PhP binding was observed under certain conditions and confirmed thermodynamically by isothermal titration calorimetry, suggesting the formation of an asymmetric quaternary structure during sequential ligation of substrates. Asymmetry in binding was also observed in isothermal titration calorimetry experiments with dephosphocoenzyme A and CoA. X-ray structures of MtPPAT in complex with PhP and the nonhydrolyzable ATP analogue adenosine-5'-[({alpha},{beta})-methyleno]triphosphate were solved to 1.57 {angstrom} and 2.68 {angstrom}, respectively. These crystal structures reveal small conformational changes in enzyme structure upon ligand binding, which may play a role in the nonrapid-equilibrium mechanism. We suggest that the proposed kinetic mechanism and asymmetric character in MtPPAT ligand binding may provide a means of reaction and pathway regulation in addition to that of the previously determined CoA feedback.« less

Effect of monofluoroacetate on renal H+ excretion in the rat.

PubMed

Simonnet, H; Gauthier, C; Pellet, M V

1979-05-01

In order to investigate the effect of monofluoroacetate (MFA) on renal H+ excretion, anesthetized rats under mannitol diuresis were given intraperitoneally MFA and some of the acido-basic status parameters were determined. Urinary pH and pCO2 did not change after MFA administration, while urinary flow rate increased. MFA induced a decrease in H+ net excretion and in ammonia excretion. Titratable acidity did not change significantly within the experiment.

Structural effects of TiO2 nanoparticles and doxorubicin on DNA and their antiproliferative roles in T47D and MCF7 cells.

PubMed

Hekmat, Azadeh; Saboury, Ali Akbar; Divsalar, Adeleh; Seyedarabi, Arefeh

2013-07-01

The structural changes in DNA caused by the combined effects of TiO2 nanoparticles (TiO2 NPs) and doxorubicin (DOX) were investigated along with their corresponding inhibitory roles in the growth of T47D and MCF7 cells. The UV-visible titration studies showed that DOX+ TiO2 NPs could form a novel complex with DNA. The data also reveal that the TiO2-DOX complex forms through a 1:4 stoichiometric ratio in solution. The values of binding constants reveal that DOX+TiO2 NPs interact more strongly with DNA as compared to TiO2 NPs or DOX alone. CD data show that DOX+TiO2 NPs can noticeably cause disturbance on DNA structure compared to TiO2 NPs or DOX alone, considering that DNA is relatively thermally stable in the condition used. The anticancer property of 0.3 µM DOX+ 60 µM TiO2 NPs and 0.4 µM DOX+ 670 µM TiO2 NPs by MTT assay and DAPI stain demonstrates that this combination can tremendously diminish proliferation of T47D and MCF7cells compared to DOX or TiO2 NPs alone. The UV-Vis absorption spectroscopy, flow cytometry and fluorescence microscopy experiments show much more enhancement of DOX uptake through the use of TiO2 NPs. These results reveal that DOX+TiO2 NPs could proffer a novel strategy for the development of promising and efficient chemotherapy agents.

A determination of the oxygen non-stoichiometry of the oxygen storage materials LnBaMn{sub 2}O{sub 5+δ} (Ln=Gd, Pr)

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

Jeamjumnunja, Kannika; Gong, Wenquan; Makarenko, Tatyana

The A-site ordered double-perovskite oxides, LnBaMn{sub 2}O{sub 5+δ} (Ln=Gd, Pr), were synthesized and investigated to understand the effect of A site cation substitution on the oxygen storage properties of these materials. The present results are compared with our previous data for YBaMn{sub 2}O{sub 5+δ}. The results clearly reveal that changing the Ln cation strongly influences the oxidation/reduction behavior of LnBaMn{sub 2}O{sub 5+δ}. Based on thermogravimetric analysis data, oxygen uptake begins at lower temperatures in both air and oxygen in compounds with Ln{sup 3+} ions larger than Y{sup 3+}. These oxides exhibit almost complete and reversible oxygen uptake/release between fully-reduced LnBaMn{submore » 2}O{sub 5} and fully-oxidized LnBaMn{sub 2}O{sub 6} during changes of the oxygen partial pressure between air and 1.99% H{sub 2}/Ar. In addition, the oxygen non-stoichiometries of GdBaMn{sub 2}O{sub 5+δ} and PrBaMn{sub 2}O{sub 5+δ} were determined as a function of pO{sub 2} at 600, 650, 700 and 750 °C by Coulometric titration at near-equilibrium conditions. The results confirm that these materials have two distinct phases on oxidation/reduction with δ≈0, 0.5 and a third phase with a range of composition with an oxygen content (5+δ) approaching ~6. The stabilities of the LnBaMn{sub 2}O{sub 5+δ} phases extend over a wide range of oxygen partial pressures (∼10{sup −25}≤pO{sub 2} (atm)≤∼1) depending on temperature. Isothermal experiments show that the larger the Ln{sup 3+} cation the lower pO{sub 2} for phase conversion. At some temperatures and pO{sub 2} conditions, the LnBaMn{sub 2}O{sub 5+δ} compounds are unstable with respect to decomposition to BaMnO{sub 3−δ} and LnMnO{sub 3}. This instability is more apparent in Coulometric titration experiments than in thermogravimetric analysis. The Coulometric titration experiments are necessarily slow in order to achieve equilibrium oxygen compositions. - Graphical abstract: Structure of LnBaMn{sub 2}O{sub 5.5} and the variation of stoichiometry of GdBaMn{sub 2}O{sub 5+x} with −log(pO{sub 2}) Display Omitted - Highlights: • Determination of the oxygen non-stoichiometry of GdBaMn{sub 2}O{sub 5+δ} and PrBaMn{sub 2}O{sub 5+δ} as a function of pO{sub 2} and T. • Establishment of pO{sub 2} ranges of stability of O{sub 5} and O{sub 5.5} at 600 °C, 650 °C, 700 °C and 750 °C. • Investigation of the kinetic instability of LnBaMn{sub 2}O{sub 5+δ} (Ln=Gd, Pr) with respect to decomposition to BaMnO{sub 3−x} and LnMnO{sub 3} • Comparison of the thermodynamics of the oxidation of LnBaMnO{sub 5} (Ln=Y, Gd, Pr) as a function of the rare earth cation size.« less

Cost-effectiveness of ezetimibe coadministration in statin-treated patients not at cholesterol goal: application to Germany, Spain and Norway.

PubMed

Cook, John R; Yin, Don; Alemao, Evo; Davies, Glenn; Krobot, Karl J; Veltri, Enrico; Lipka, Leslie; Badia, Xavier

2004-01-01

Despite the growing use of statins, many hypercholesterolaemic patients fail to reach their lipid goal and remain at elevated risk of coronary heart disease (CHD). Alternative treatment strategies, such as ezetimibe coadministration and statin titration, can help patients achieve greater lipid control, and thereby lower their CHD risk. But is it cost effective to more aggressively lower cholesterol levels across a broad range of current statin users? Using a decision-analytic model based on epidemiological and clinical trials data, we project the lifetime benefit and cost of alternative lipid-lowering treatment strategies for CHD and non-CHD diabetic patients in Germany, Spain and Norway. It is projected that from 40% to 76% of these patients who have failed to reach their lipid goal with their current statin treatment will be able to reach their goal with ezetimibe coadministration; this represents a gain of up to an additional absolute 14% who will be able to reach their goal compared with a 'titrate to goal' strategy where patients are titrated in order to reach their lipid goal (up to the maximum approved dose). For CHD patients, the estimated incremental cost-effectiveness ratio for ezetimibe coadministration is under Euro 18 000 per life-year gained (Euro/LYG) and 26 000 Euro/LYG compared with strategies based on the observed titration rates and the aggressive 'titrate to goal' strategy, respectively; for non-CHD diabetic patients, these ratios are under 26 000 Euro/LYG and 48 000 Euro/LYG for ezetimibe coadministration compared with the two titration strategies. Compared with statin titration, ezetimibe coadministration is projected to be cost effective in the populations and countries studied.

Evaluation of synergistic effects of resynchronization therapy and a β-blocker up-titration strategy based on a predefined patient-management program: the RESTORE study.

PubMed

Palmisano, Pietro; Ammendola, Ernesto; D'Onofrio, Antonio; Accogli, Michele; Calò, Leonardo; Ruocco, Antonio; Rapacciuolo, Antonio; Del Giorno, Giuseppe; Bianchi, Valter; Malacrida, Maurizio; Valsecchi, Sergio; Gronda, Edoardo

2015-01-01

Prior studies have suggested that a substantial number of eligible heart failure (HF) patients fail to receive β-blocker therapy, or receive it at a suboptimal dose. The aim of this study is to assess the benefit of a predefined management program designed for β-blocker up-titration, evaluating the synergistic effect of cardiac resynchronization therapy (CRT) and β-blockers in a HF population. The Resynchronization Therapy and β-Blocker Titration (RESTORE) study is a prospective, case-control, multicenter cohort study designed to test the hypothesis that a β-blocker up-titration strategy based on a predefined management program maximizes the beneficial effect of CRT, increasing the number of patients reaching the target dose of β-blockers and improving their clinical outcome. All study patients receive an implantable defibrillator for CRT delivery in accordance with current guidelines. Enrollments started in December 2011 and are scheduled to end in December 2014. Approximately 250 consecutive patients will be prospectively enrolled in 6 Italian centers and followed up for 24 months after implantation. The primary endpoint is to demonstrate that CRT may allow titration of β-blockers until the optimal dose, or at least to the effective dose, in patients with HF. This study might provide important information about the benefit of a predefined management program for β-blocker up-titration in patients receiving CRT. Moreover, assessment of health-care utilization and the consumption of resources will allow estimating the potential utility of remote monitoring by means of an automated telemedicine system in facilitating the titration of β-blockers in comparison with a standard in-hospital approach. © 2015 Wiley Periodicals, Inc.

Clinical Outcomes of Continuation of Metformin Titration Instructions with Electronic Prescribing.

PubMed

Delate, Thomas; Rader, Nathan; Rawlings, Julia E; Smith, Karen; Herner, Sheryl J

2015-06-01

Anecdotal evidence suggests that metformin titration instructions are not being updated and refill requests are approved without modification of the titration instructions such that the titration instructions is continued for patients newly initiated on metformin. This was a retrospective cohort analysis of adult patients who received newly initiated metformin pharmacotherapy. Patients were followed from their initial metformin purchase through two subsequent metformin refill purchases. Outcomes, including the 3-year incidence rate of patients with at least one set of continued titration instructions and proportions of patients with at least one gastrointestinal adverse effect (AE) and those with an elevated glucose measurement at follow-up, were assessed during the time period between patients' second and third metformin purchases. Analyses were performed comparing the exposure (i.e., patients with continued instructions) group to the control (i.e., patients without continued instructions) group. The exposure group had a higher mean age and chronic disease score but lower metformin starting dose than the control group (all p < 0.05). The 3-year incidence rate of patients with at least one continuation of titration instructions was 60.3 % (95 % CI 58.3-62.3). Gastrointestinal AEs were rare with equivalent proportions of patients in each group experiencing an event (p > 0.05). Control patients (48.7 % of patients with a measurement) were more likely to have had poorly controlled glucose than exposure patients (35.7 % of patients with a measurement) (p < 0.001). A high rate of continuation of titration instructions for patients newly initiated on metformin was observed; however, such continuation did not negatively affect clinical outcomes.

Barriers to Beta-Blocker Use and Up-Titration Among Patients with Heart Failure with Reduced Ejection Fraction.

PubMed

Levitan, Emily B; Van Dyke, Melissa K; Loop, Matthew Shane; O'Beirne, Ronan; Safford, Monika M

2017-12-01

For patients with heart failure with reduced ejection fraction (HFrEF), guidelines recommend use of beta-blockers with gradual up-titration. However, many patients with HFrEF do not use beta-blockers and up-titration is rare. Our purpose was to identify and rank barriers to beta-blocker use and up-titration from the perspective of primary care physicians. We conducted 4 moderated, structured group discussions among 19 primary care physicians using the nominal group technique; 16 participants also completed a survey. Participants generated lists of barriers to beta-blocker use and up-titration among patients with HFrEF. Each participant had six votes with three votes assigned to the item ranked most important, two to the second most important item, and one to the third most important item. Investigators characterized items into themes. The percentage of available votes was calculated for each theme. Fifteen of 16 participating primary care physicians who completed the survey reported that management of beta-blockers was their responsibility. Treatment/side effects, particularly hypotension, were identified as the most important barrier for beta-blocker use (72% of available votes) followed by polypharmacy (11%), healthcare system barriers (10%), and comorbidities (6%). Barriers to up-titration included treatment/side effects (49% of available votes), patient communication/buy-in (21%), polypharmacy (13%), and healthcare system barriers (8%). Many barriers to guideline concordant use of beta-blockers among patients with HFrEF identified by primary care providers are not readily modifiable. Addressing these barriers may require development, testing, and dissemination of protocols for beta-blocker initiation and up-titration that are safe and appropriate in primary care.

Entire-Dataset Analysis of NMR Fast-Exchange Titration Spectra: A Mg2+ Titration Analysis for HIV-1 Ribonuclease H Domain.

PubMed

Karki, Ichhuk; Christen, Martin T; Spiriti, Justin; Slack, Ryan L; Oda, Masayuki; Kanaori, Kenji; Zuckerman, Daniel M; Ishima, Rieko

2016-12-15

This article communicates our study to elucidate the molecular determinants of weak Mg 2+ interaction with the ribonuclease H (RNH) domain of HIV-1 reverse transcriptase in solution. As the interaction is weak (a ligand-dissociation constant >1 mM), nonspecific Mg 2+ interaction with the protein or interaction of the protein with other solutes that are present in the buffer solution can confound the observed Mg 2+ -titration data. To investigate these indirect effects, we monitored changes in the chemical shifts of backbone amides of RNH by recording NMR 1 H- 15 N heteronuclear single-quantum coherence spectra upon titration of Mg 2+ into an RNH solution. We performed the titration under three different conditions: (1) in the absence of NaCl, (2) in the presence of 50 mM NaCl, and (3) at a constant 160 mM Cl - concentration. Careful analysis of these three sets of titration data, along with molecular dynamics simulation data of RNH with Na + and Cl - ions, demonstrates two characteristic phenomena distinct from the specific Mg 2+ interaction with the active site: (1) weak interaction of Mg 2+ , as a salt, with the substrate-handle region of the protein and (2) overall apparent lower Mg 2+ affinity in the absence of NaCl compared to that in the presence of 50 mM NaCl. A possible explanation may be that the titrated MgCl 2 is consumed as a salt and interacts with RNH in the absence of NaCl. In addition, our data suggest that Na + increases the kinetic rate of the specific Mg 2+ interaction at the active site of RNH. Taken together, our study provides biophysical insight into the mechanism of weak metal interaction on a protein.

Improved methylene blue two-phase titration method for determining cationic surfactant concentration in high-salinity brine.

PubMed

Cui, Leyu; Puerto, Maura; López-Salinas, José L; Biswal, Sibani L; Hirasaki, George J

2014-11-18

The methylene blue (MB) two-phase titration method is a rapid and efficient method for determining the concentrations of anionic surfactants. The point at which the aqueous and chloroform phases appear equally blue is called Epton's end point. However, many inorganic anions, e.g., Cl(-), NO3(-), Br(-), and I(-), can form ion pairs with MB(+) and interfere with Epton's end point, resulting in the failure of the MB two-phase titration in high-salinity brine. Here we present a method to extend the MB two-phase titration method for determining the concentration of various cationic surfactants in both deionized water and high-salinity brine (22% total dissolved solid). A colorless end point, at which the blue color is completely transferred from the aqueous phase to the chloroform phase, is proposed as titration end point. Light absorbance at the characteristic wavelength of MB is measured using a spectrophotometer. When the absorbance falls below a threshold value of 0.04, the aqueous phase is considered colorless, indicating that the end point has been reached. By using this improved method, the overall error for the titration of a permanent cationic surfactant, e.g., dodecyltrimethylammonium bromide, in deionized (DI) water and high-salinity brine is 1.274% and 1.322% with limits of detection (LOD) of 0.149 and 0.215 mM, respectively. Compared to the traditional acid-base titration method, the error of this improved method for a switchable cationic surfactant, e.g., tertiary amine surfactant (Ethomeen C12), is 2.22% in DI water and 0.106% with LOD of 0.369 and 0.439 mM, respectively.

Barriers to and enablers of insulin self-titration in adults with Type 2 diabetes: a qualitative study.

PubMed

McBain, H; Begum, S; Rahman, S; Mulligan, K

2017-02-01

To identify the barriers to and enablers of effective insulin self-titration in people with Type 2 diabetes. A qualitative semi-structured interview approach was used. Questions were structured according to the Theoretical Domains Framework, which outlines 14 domains that can act as barriers to and enablers of changing behaviour. Interviews were audio-recorded and transcribed verbatim. The data were coded according to the 14 domains, belief statements were created within each domain, and a frequency count of the most reported barriers and enablers was then carried out. Analyses were conducted by two researchers, and discrepancies agreed with a third researcher. A total of 18 adults with Type 2 diabetes took part in an interview. The majority were of South-Asian ethnicity (n = 8) and were men (n = 12). Their mean age was 61 years old. The mean duration of diabetes was 16 years and time on insulin 9 years. Inter-rater reliability for each of the domains varied (29-100%). The most frequently reported domains were Social Influence and Beliefs about Consequences; the least frequently reported were Optimism and Reinforcement. Interviewees reported receiving support to self-titrate from a range of sources. Self-titrating was perceived to have a range of both positive and negative consequences, as was not titrating. The findings highlight that those interviewed experienced a range of barriers and enablers when attempting to self-titrate. Improved education and training when initiating insulin treatment among adults with Type 2 diabetes, and throughout their journey on insulin therapy could help identify and address these barriers in order to optimize self-titration. © 2016 Diabetes UK.

Labeling Cells with Silver/Dendrimer Nanocomposites

DTIC Science & Technology

2005-01-01

used in further studies without additional purification. Potentiometric titrations were performed manually, under nitrogen atmosphere, at room...transmits light between 465 and 485 nm. Results and Discussion Figure IA presents potentiometric titration curves of Ag+-PAMAM_E5.NH 2 systems mixed at 15:1... Potentiometric titration curves of PAMAM_E5.NH 2 (circles) Ag+-PAMAME5.NH 2 30:1 (squares) and Ag+-PAMAME5.NH2 45:1 systems (triangles). B - UV-vis spectra of UV

Molecular Weight Measurement of Biobased Furan Polyamides via Non-Aqueous Potentiometric Titration

DTIC Science & Technology

2013-06-01

electromagnetic fields, all titrations were completed in a chemical hood, which acted as a Faraday cage (a shield used to blocks external static and...while using DMF as a solvent. Additionally, no Faraday cage was used in the experimental setup, so the titrations were conducted inside the chemical...monomer was becoming more soluble in glacial acetic acid and the amount of chlorobenzene had less of an effect on the solution properties (i.e

The benefit of HH during the CPAP titration in the cool sleeping environment.

PubMed

Li, Yayong; Wang, Yina

2016-12-01

Upper airway symptom associated with continuous positive airway pressure (CPAP) treatment is an important factor influencing CPAP adherence. There are conflicting data on the effect of a heated humidifier (HH) during CPAP titration for patients with obstructive sleep apnea hypopnea syndrome (OSAHS). This study investigated the effects of HH during CPAP titration in the cool sleeping environment. Forty newly diagnosed OSAHS patients who received CPAP titration in the cool sleeping environment were randomly assigned to HH and non-HH groups. A questionnaire was used to evaluate upper airway symptoms, satisfaction with initial CPAP treatment, and willingness to further use CPAP. Some therapy parameters including leak, apnea hypopnea index (AHI) reduction, and optimal CPAP pressure level were analyzed. We compared these subjective and objective data between the two groups. In subjective sensation, the use of HH can alleviate upper airway symptoms associated with CPAP titration (P < 0.001). The HH group has benefit in satisfaction with initial CPAP treatment (P < 0.001) and further willingness to use CPAP (P < 0.01), although there were no significant differences in leak, AHI reduction, and optimal CPAP pressure between the two groups. The use of HH is recommended during CPAP titration in the cool sleeping environment because of its benefit in the treatment of upper airway symptoms associated with CPAP therapy and improvement of the CPAP acceptance.

Modeling the acid-base surface chemistry of montmorillonite.

PubMed

Bourg, Ian C; Sposito, Garrison; Bourg, Alain C M

2007-08-15

Proton uptake on montmorillonite edge surfaces can control pore water pH, solute adsorption, dissolution kinetics and clay colloid behavior in engineered clay barriers and natural weathering environments. Knowledge of proton uptake reactions, however, is currently limited by strong discrepancies between reported montmorillonite titration data sets and by conflicting estimates of edge structure, reactivity and electrostatics. In the present study, we show that the apparent discrepancy between titration data sets results in large part from the widespread use of an erroneous assumption of zero specific net proton surface charge at the onset of titration. Using a novel simulation scheme involving a surface chemistry model to simulate both pretreatment and titration, we find that montmorillonite edge surface chemistry models that account for the "spillover" of electrostatic potential from basal onto edge surfaces and for the stabilization of deprotonated Al-Si bridging sites through bond-length relaxation at the edge surface can reproduce key features of the best available experimental titration data (the influence of pretreatment conditions on experimental results, the absence of a point of zero salt effect, buffer capacity in the acidic pH range). However, no combination of current models of edge surface structure, reactivity and electrostatics can quantitatively predict, without fitted parameters, the experimental titration data over the entire range of pH (4.5 to 9) and ionic strength (0.001 to 0.5 mol dm(-3)) covered by available data.

Switching to aripiprazole in outpatients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues with risperidone: a randomized, multicentre, open-label study.

PubMed

Ryckmans, V; Kahn, J P; Modell, S; Werner, C; McQuade, R D; Kerselaers, W; Lissens, J; Sanchez, R

2009-05-01

This study evaluated the safety/tolerability and effectiveness of aripiprazole titrated-dose versus fixed-dose switching strategies from risperidone in patients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues. Patients were randomized to an aripiprazole titrated-dose (starting dose 5 mg/day) or fixed-dose (dose 15 mg/day) switching strategy with risperidone down-tapering. Primary endpoint was rate of discontinuation due to adverse events (AEs) during the 12-week study. Secondary endpoints included positive and negative syndrome scale (PANSS), clinical global impressions - improvement of illness scale (CGI-I), preference of medication (POM), subjective well-being under neuroleptics (SWN-K) and GEOPTE (Grupo Español para la Optimización del Tratamiento de la Esquizofrenia) scales. Rates of discontinuations due to AEs were similar between titrated-dose and fixed-dose strategies (3.5% vs. 5.0%; p=0.448). Improvements in mean PANSS total scores were similar between aripiprazole titrated-dose and fixed-dose strategies (-14.8 vs. -17.2; LOCF), as were mean CGI-I scores (2.9 vs. 2.8; p=0.425; LOCF) and SWN-K scores (+8.6 vs.+10.3; OC,+7.8 vs.+9.8; LOCF). Switching can be effectively and safely achieved through a titrated-dose or fixed-dose switching strategy for aripiprazole, with down-titration of risperidone.

A digital image-based method for determining of total acidity in red wines using acid-base titration without indicator.

PubMed

Tôrres, Adamastor Rodrigues; Lyra, Wellington da Silva; de Andrade, Stéfani Iury Evangelista; Andrade, Renato Allan Navarro; da Silva, Edvan Cirino; Araújo, Mário César Ugulino; Gaião, Edvaldo da Nóbrega

2011-05-15

This work proposes the use of digital image-based method for determination of total acidity in red wines by means of acid-base titration without using an external indicator or any pre-treatment of the sample. Digital images present the colour of the emergent radiation which is complementary to the radiation absorbed by anthocyanines present in wines. Anthocyanines change colour depending on the pH of the medium, and from the variation of colour in the images obtained during titration, the end point can be localized with accuracy and precision. RGB-based values were employed to build titration curves, and end points were localized by second derivative curves. The official method recommends potentiometric titration with a NaOH standard solution, and sample dilution until the pH reaches 8.2-8.4. In order to illustrate the feasibility of the proposed method, titrations of ten red wines were carried out. Results were compared with the reference method, and no statistically significant difference was observed between the results by applying the paired t-test at the 95% confidence level. The proposed method yielded more precise results than the official method. This is due to the trivariate nature of the measurements (RGB), associated with digital images. Copyright © 2011 Elsevier B.V. All rights reserved.

End-point detection in potentiometric titration by continuous wavelet transform.

PubMed

Jakubowska, Małgorzata; Baś, Bogusław; Kubiak, Władysław W

2009-10-15

The aim of this work was construction of the new wavelet function and verification that a continuous wavelet transform with a specially defined dedicated mother wavelet is a useful tool for precise detection of end-point in a potentiometric titration. The proposed algorithm does not require any initial information about the nature or the type of analyte and/or the shape of the titration curve. The signal imperfection, as well as random noise or spikes has no influence on the operation of the procedure. The optimization of the new algorithm was done using simulated curves and next experimental data were considered. In the case of well-shaped and noise-free titration data, the proposed method gives the same accuracy and precision as commonly used algorithms. But, in the case of noisy or badly shaped curves, the presented approach works good (relative error mainly below 2% and coefficients of variability below 5%) while traditional procedures fail. Therefore, the proposed algorithm may be useful in interpretation of the experimental data and also in automation of the typical titration analysis, specially in the case when random noise interfere with analytical signal.

Potentiometric Titrations for Measuring the Capacitance of Colloidal Photodoped ZnO Nanocrystals.

PubMed

Brozek, Carl K; Hartstein, Kimberly H; Gamelin, Daniel R

2016-08-24

Colloidal semiconductor nanocrystals offer a unique opportunity to bridge molecular and bulk semiconductor redox phenomena. Here, potentiometric titration is demonstrated as a method for quantifying the Fermi levels and charging potentials of free-standing colloidal n-type ZnO nanocrystals possessing between 0 and 20 conduction-band electrons per nanocrystal, corresponding to carrier densities between 0 and 1.2 × 10(20) cm(-3). Potentiometric titration of colloidal semiconductor nanocrystals has not been described previously, and little precedent exists for analogous potentiometric titration of any soluble reductants involving so many electrons. Linear changes in Fermi level vs charge-carrier density are observed for each ensemble of nanocrystals, with slopes that depend on the nanocrystal size. Analysis indicates that the ensemble nanocrystal capacitance is governed by classical surface electrical double layers, showing no evidence of quantum contributions. Systematic shifts in the Fermi level are also observed with specific changes in the identity of the charge-compensating countercation. As a simple and contactless alternative to more common thin-film-based voltammetric techniques, potentiometric titration offers a powerful new approach for quantifying the redox properties of colloidal semiconductor nanocrystals.

Origin of two time-scale regimes in potentiometric titration of metal oxides. A replica kinetic Monte Carlo study.

PubMed

Zarzycki, Piotr; Rosso, Kevin M

2009-06-16

Replica kinetic Monte Carlo simulations were used to study the characteristic time scales of potentiometric titration of the metal oxides and (oxy)hydroxides. The effect of surface heterogeneity and surface transformation on the titration kinetics were also examined. Two characteristic relaxation times are often observed experimentally, with the trailing slower part attributed to surface nonuniformity, porosity, polymerization, amorphization, and other dynamic surface processes induced by unbalanced surface charge. However, our simulations show that these two characteristic relaxation times are intrinsic to the proton-binding reaction for energetically homogeneous surfaces, and therefore surface heterogeneity or transformation does not necessarily need to be invoked. However, all such second-order surface processes are found to intensify the separation and distinction of the two kinetic regimes. The effect of surface energetic-topographic nonuniformity, as well dynamic surface transformation, interface roughening/smoothing were described in a statistical fashion. Furthermore, our simulations show that a shift in the point-of-zero charge is expected from increased titration speed, and the pH-dependence of the titration measurement error is in excellent agreement with experimental studies.

Trace analysis of acids and bases by conductometric titration with multiparametric non-linear regression.

PubMed

Coelho, Lúcia H G; Gutz, Ivano G R

2006-03-15

A chemometric method for analysis of conductometric titration data was introduced to extend its applicability to lower concentrations and more complex acid-base systems. Auxiliary pH measurements were made during the titration to assist the calculation of the distribution of protonable species on base of known or guessed equilibrium constants. Conductivity values of each ionized or ionizable species possibly present in the sample were introduced in a general equation where the only unknown parameters were the total concentrations of (conjugated) bases and of strong electrolytes not involved in acid-base equilibria. All these concentrations were adjusted by a multiparametric nonlinear regression (NLR) method, based on the Levenberg-Marquardt algorithm. This first conductometric titration method with NLR analysis (CT-NLR) was successfully applied to simulated conductometric titration data and to synthetic samples with multiple components at concentrations as low as those found in rainwater (approximately 10 micromol L(-1)). It was possible to resolve and quantify mixtures containing a strong acid, formic acid, acetic acid, ammonium ion, bicarbonate and inert electrolyte with accuracy of 5% or better.

Solution and fluorescence properties of symmetric dipicolylamine-containing dichlorofluorescein-based Zn2+ sensors.

PubMed

Wong, Brian A; Friedle, Simone; Lippard, Stephen J

2009-05-27

The mechanism by which dipicolylamine (DPA) chelate-appended fluorophores respond to zinc was investigated by the synthesis and study of five new analogues of the 2',7'-dichlorofluorescein-based Zn(2+) sensor Zinpyr-1 (ZP1). With the use of absorption and emission spectroscopy in combination with potentiometric titrations, a detailed molecular picture has emerged of the Zn(2+) and H(+) binding properties of the ZP1 family of sensors. The two separate N(3)O donor atom sets on ZP1 converge to form binding pockets in which all four heteroatoms participate in coordination to either Zn(2+) or protons. The position of the pyridyl group nitrogen atom, 2-pyridyl or 4-pyridyl, has a large impact on the fluorescence response of the dyes to protons despite relatively small changes in pK(a) values. The fluorescence quenching effects of such multifunctional electron-donating units are often taken as a whole. Despite the structural complexity of ZP1, however, we provide evidence that the pyridyl arms of the DPA appendages participate in the quenching process, in addition to the contribution from the tertiary nitrogen amine atom. Potentiometric titrations reveal ZP1 dissociation constants (K(d)) for Zn(2+) of 0.04 pM and 1.2 nM for binding to the first and second binding pockets of the ligand, respectively, the second of which correlates with the value observed by fluorescence titration. This result demonstrates that both binding pockets of this symmetric, ditopic sensor need to be occupied in order for full fluorescence turn-on to be achieved. These results have significant implications for the design and implementation of fluorescent sensors for studies of mobile zinc ions in biology.

Investigation of the interaction of iron(III) complexes with dAMP by ESI-MS, MALDI-MS and potentiometric titration: insights into synthetic nuclease behavior.

PubMed

Fernandes, Christiane; Oliveira Moreira, Rafaela; Lube, Leonardo M; Horn, Adolfo; Szpoganicz, Bruno; Sherrod, Stacy; Russell, David H

2010-06-07

We report herein the characterization by electrospray ionization (ESI) mass spectrometry (MS), matrix assisted laser desorption ionization (MALDI-MS) and potentiometric titration of three iron(III) compounds: [Fe(III)(HPClNOL)Cl2]·NO3 (1), [Cl(HPClNOL)Fe(III)-(μ-O)-Fe(III)(HPClNOL)Cl]·Cl2·H2O (2) and [(SO4)(HPClNOL)Fe(III)-(μ-O)-Fe(III)(HPClNOL)(SO4)]·6H2O (3), where HPClNOL= 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol). Despite the fact that the compounds have distinct structures in solid state and non-buffered solution, all compounds present similar ESI and MALDI mass spectra in a buffered medium (pH 7.0). At this pH, the species [(PClNOL)Fe(III)-(μ-O)-Fe(III)(PClNOL)](2+) (m/z 354) was observed for all the compounds under investigation. Potentiometric titration confirms a similar behavior for all compounds, indicating that the dihydroxo form [(OH)(HPClNOL)Fe(III)-(μ-O)-Fe(III)(HPClNOL)(OH)](2+) is the major species at pH 7.0, for all the compounds. The products of the interaction between compounds (1), (2) and (3) and dAMP (2'-deoxyadenosine-5'-monophosphate) in a buffered medium (pH 7.0) were identified by MALDI-MS/MS. The fragmentation data obtained by MS/MS allow one to identify the nature of the interaction between the iron(III) compounds and dAMP, revealing the direct interaction between the iron center and phosphate groups.

Cell surface groups of two picocyanobacteria strains studied by zeta potential investigations, potentiometric titration, and infrared spectroscopy.

PubMed

Dittrich, Maria; Sibler, Sabine

2005-06-15

In order to clarify the role of picocyanobacteria in aquatic biogeochemical processes (e.g., calcite precipitation), cell surface properties need to be investigated. An experimental study of the cell surface characteristics of two Synechococcus-type unicellular autotrophic picocyanobacterial strains was carried out. One strain was isolated from Lake Plon and contained phycocyanin, the other strain came from Lago Maggiore and was rich in phycoerythrin. Potentiometric titrations were conducted to determine the different types of sites present on the bacteria cell walls. Infrared spectroscopy allowed characterization of the various functional groups (RNH(2), RCOOH, ROH, RPO(2)) and investigations of zeta potential provided insight into the isoelectrical points of the strains. Titrations reveal three distinct sites on the bacterial surfaces of phycocyanin- and phycoerythrin-rich strains with pK values of 4.8+/-0.3/5.0+/-0.2, 6.6+/-0.2/6.7+/-0.4, and 8.8+/-0.1/8.7+/-0.2, corresponding to carboxyl, phosphate, and amine groups with surface densities of 2.6+/-0.4/7.4+/-1.6 x 10(-4), 1.9+/-0.5/4.4+/-0.8 x 10(-4), and 2.5+/-0.4/4.8+/-0.7 x 10(-4) mol/g of dry bacteria. The deprotonation constants are similar to those of bacterial strains and site densities are also within an order of magnitude of other strains. The phycoerythrin-rich strain had a higher number of binding sites than the phycocyanin-rich strain. The results showed that picocyanobacteria may adsorb either calcium cations or carbonate anions and therefore strongly influence the biogeochemical cycling of calcite in pelagic systems.

Use of the sulfide mineral pyrite as electrochemical sensor in non-aqueous solutions: potentiometric titration of weak acids in acetonitrile, propionitrile and benzonitrile.

PubMed

Mihajlović, Ljiljana; Nikolić-Mandić, Snezana; Vukanović, Branislav; Mihajlović, Randel

2009-03-01

Natural monocrystalline pyrite as a new indicator electrode for the potentiometric titration of weak acids in acetonitrile, propionitrile and benzonitrile was studied. The investigated electrode showed a linear dynamic response for p-toluenesulfonic acid concentrations in the range from 0.1 to 0.001 M, with a Nernstian slope of 74 mV per decade. Sodium methylate, potassium hydroxide and tetrabutylammonium hydroxide (TBAH) proved to be very suitable titrating agent for this titration. The response time was less than (11 s) and the lifetime of the electrode is long. The advantages of the electrode are log-term stability, fast response, and reproducibility, while the sensor is easy to prepare and of low cost.

Determination of arsenate and organic arsenic via potentiometric titration of its heteropoly anions.

PubMed

Metelka, R; Slavíková, S; Vytras, K

2002-08-16

Determination of arsenate based on its conversion to molybdoarsenate heteropoly anions followed by potentiometric titration is described. The titration is realized on the ion-pairing principle using cetylpyridinium chloride (or an analogous titrant containing a lipophilic cation), and is monitored by a carbon paste electrode, although other liquid-polymeric membrane-based electrodes can also be used. Calibration plots of the titrant end-point consumption versus concentration of arsenic were constructed and used to evaluate the content of arsenic in aqueous samples. The method could be applied in the analyses of samples with quite low arsenic content (amounts approximately 10 mug As in 50 cm(3) could be titrated). Organic arsenic was determined analogously after the Schöniger combustion of the sample and conversion of its arsenic to arsenate.

Pyrrole-indolinone SU11652 targets the nucleoside diphosphate kinase from Leishmania parasites.

PubMed

Vieira, Plínio Salmazo; Souza, Tatiana de Arruda Campos Brasil; Honorato, Rodrigo Vargas; Zanphorlin, Letícia Maria; Severiano, Kelven Ulisses; Rocco, Silvana Aparecida; de Oliveira, Arthur Henrique Cavalcante; Cordeiro, Artur Torres; Oliveira, Paulo Sérgio Lopes; de Giuseppe, Priscila Oliveira; Murakami, Mário Tyago

2017-07-01

Nucleoside diphosphate kinases (NDKs) are key enzymes in the purine-salvage pathway of trypanosomatids and have been associated with the maintenance of host-cell integrity for the benefit of the parasite, being potential targets for rational drug discovery and design. The NDK from Leishmania major (LmNDK) and mutants were expressed and purified to homogeneity. Thermal shift assays were employed to identify potential inhibitors for LmNDK. Calorimetric experiments, site-directed mutagenesis and molecular docking analysis were performed to validate the interaction and to evaluate the structural basis of ligand recognition. Furthermore, the anti-leishmanial activity of the newly identified and validated compound was tested in vitro against different Leishmania species. The molecule SU11652, a Sunitinib analog, was identified as a potential inhibitor for LmNDK and structural studies indicated that this molecule binds to the active site of LmNDK in a similar conformation to nucleotides, mimicking natural substrates. Isothermal titration calorimetry experiments combined with site-directed mutagenesis revealed that the residues H50 and H117, considered essential for catalysis, play an important role in ligand binding. In vitro cell studies showed that SU11652 had similar efficacy to Amphotericin b against some Leishmania species. Together, our results indicate the pyrrole-indolinone SU11652 as a promising scaffold for the rational design of new drugs targeting the enzyme NDK from Leishmania parasites. Copyright © 2017 Elsevier Inc. All rights reserved.

Solution structures and backbone dynamics of Escherichia coli rhodanese PspE in its sulfur-free and persulfide-intermediate forms: implications for the catalytic mechanism of rhodanese.

PubMed

Li, Hongwei; Yang, Fan; Kang, Xue; Xia, Bin; Jin, Changwen

2008-04-15

Rhodanese catalyzes the sulfur-transfer reaction that transfers sulfur from thiosulfate to cyanide by a double-displacement mechanism, in which an active cysteine residue plays a central role. Previous studies indicated that the phage-shock protein E (PspE) from Escherichia coli is a rhodanese composed of a single active domain and is the only accessible rhodanese among the three single-domain rhodaneses in E. coli. To understand the catalytic mechanism of rhodanese at the molecular level, we determined the solution structures of the sulfur-free and persulfide-intermediate forms of PspE by nuclear magnetic resonance (NMR) spectroscopy and identified the active site by NMR titration experiments. To obtain further insights into the catalytic mechanism, we studied backbone dynamics by NMR relaxation experiments. Our results demonstrated that the overall structures in both sulfur-free and persulfide-intermediate forms are highly similar, suggesting that no significant conformational changes occurred during the catalytic reaction. However, the backbone dynamics revealed that the motional properties of PspE in its sulfur-free form are different from the persulfide-intermediate state. The conformational exchanges are largely enhanced in the persulfide-intermediate form of PspE, especially around the active site. The present structural and biochemical studies in combination with backbone dynamics provide further insights in understanding the catalytic mechanism of rhodanese.

Disciplining addictions: the bio-politics of methadone and heroin in the United States.

PubMed

Bourgois, P

2000-06-01

Biomedical understanding of methadone as a magic-bullet pharmacological block to the euphoric effects of heroin is inconsistent with epidemiological and clinical data. An ethnographic perspective on the ways street-based heroin addicts experience methadone reveals the quagmire of power relations that shape drug treatment in the United States. The phenomenon of the methadone clinic is an unhappy compromise between competing discourses: A criminalizing morality versus a medicalizing model of addiction-as-a-brain-disease. Treatment in this context becomes a hostile exercise in disciplining the unruly misuses of pleasure and in controlling economically unproductive bodies. Most of the biomedical and epidemiological research literature on methadone obscures these power dynamics by technocratically debating dosage titrations in a social vacuum. A foucaultian critique of the interplay between power and knowledge might dismiss debates over the Swiss experiments with heroin prescription as merely one more version of biopower disciplining unworthy bodies. Foucault's ill-defined concept of the specific intellectual as someone who confronts power relations on a practical technical level, however, suggests there can be a role for political as well as theoretical engagement with debates in the field of applied substance abuse treatment. Meanwhile, too many heroin addicts who are prescribed methadone in the United States suffer negative side effects that range from an accentuated craving for polydrug abuse to a paralyzing sense of impotence and physical and emotional discomfort.

Does the commonly used pH-stat method with back titration really quantify the enzymatic digestibility of lipid drug delivery systems? A case study on solid lipid nanoparticles (SLN).

PubMed

Heider, Martha; Hause, Gerd; Mäder, Karsten

2016-12-01

Enzymatic digestion of lipid drug carriers is very important. Commonly, pancreatin induced formation of fatty acids is monitored by the pH-stat method, which provides a fast, but unspecific readout. However, according to the literature, the pKa values of long chain fatty acids are strongly dependent on the local environment and might vary between 4.2 and 10.15. The high pKa values would lead to an incomplete detection of the lipid digestion and false results. In order to investigate these issues in more detail, we produced cetyl palmitate solid lipid nanoparticles (CP-SLN) stabilized with poloxamer 188 or polysorbate 80. The digestion of CP-SLN was investigated by two different and independent readouts. A HPTLC assay was used in addition to the pH-stat method (with or without back titration). An incomplete digestion of CP-SLN was observed with all methods. Partial digestion of polysorbate 80 contributed to the formation of fatty acids. Depending on the investigated system and the experimental conditions (FaSSIF or FeSSIF) the results of both readout methods were comparable or not. For example, in FeSSIF conditions, the values detected by HPTLC were roughly twice as high as the pH-stat results. Our findings on solid lipids agree with data from Helbig et al. on lipid emulsions, where a gas chromatography method detected much higher values than the pH-stat assay (Food Hydrocoll. 28 (2012) 10-19). The results of our pH-stat experiments with back titration at different pH values showed increased values for fatty acids from pH 7.5 to pH 10. The values obtained by back titration at high pH values (pH 9 or higher) did exceed the digestion values measured by HPTLC. Therefore, we conclude that the pH-stat method might give the same results as more specific reference methods, but it might also both under- (without back titration) or overestimate (with back titration) the enzymatic digestion of lipid drug delivery systems. A further outcome of our study was the proof that lipase is the main enzyme involved in the digestion of the solid wax cetyl palmitate, because CP-SLN loaded with the inhibitor orlistat were not digestible and gave similar values as the corresponding control samples. In summary, our experimental results confirm the theoretical considerations (based on published pKa values) that the pH-stat method will not detect all fatty acids quantitatively. The very strong impact of the local environment on the pKa value of long chain fatty acids is a serious limitation and might lead to misleading interpretations. Copyright © 2016 Elsevier B.V. All rights reserved.

Ln3+-Catalyzed Alcoholysis of Organophosphates: New Methodology for the Catalytic Transformation of Phosphorus Pesticides and CW Agents

DTIC Science & Technology

2007-03-14

1770. 9. Graham T. T. Gibson, Mark F. Mohamed, Alexei A. Neverov and R. S. Brown*, “ Potentiometric titration of metal ions in ethanol.” Inorganic...81, 495-504. 2 . Graham T. T. Gibson, Mark F. Mohamed, Alexei A. Neverov and R. S. Brown*, “ Potentiometric titration of metal ions in ethanol...necessary to understand the determination of pH in these anhydrous solvents, and then to undertake detailed studies of titration of metal

Advanced titration to treat a floppy epiglottis in selective upper airway stimulation.

PubMed

Heiser, Clemens

2016-09-01

The following report presents a case of a patient with high residual apnea-hypopnea index at 6 months following implantation of an upper airway stimulation device who improved significantly after advanced titration via drug-induced sedated endoscopy by changing the electrode configuration for stimulation from bipolar to monopolar. This case demonstrates the utility of postsurgical advanced titration to optimize programming settings for improved clinical outcomes. Laryngoscope, 126:S22-S24, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Evaluation of Expedient Decontamination Options with Activated Peroxide-based Liquid Sporicides

DTIC Science & Technology

2013-02-05

H2O2 (6% immediately post mixing) was verified by potassium permanganate titration (see Appendix B, DTRL MOP #3177) and then monitored throughout testing...H2O2 Concentration in AHP The concentration of H2O2 in the AHP solution was verified by analyzing with the potassium permanganate (KMnO4) titration...Concentration of H2O2 in the working decontamination solution was measured via permanganate titration in 24 samples of AHP taken from the backpack sprayer

Report of a patient chewing fentanyl patches who was titrated onto methadone

PubMed Central

Dale, Eric; Ashby, Fleur; Seelam, Kalyan

2009-01-01

This case report discusses the clinical presentation and management of a patient presenting to substance misuse services reporting chewing fentanyl patches in addition to wearing them transdermally. The patient was successfully titrated onto methadone 30 mg. Only one previously reported case of an individual chewing fentanyl patches was found in the literature; no case reports were found where treatment involved titrating the patient onto methadone. The pharmacology and illicit use of fentanyl are also considered. PMID:22114625

Calorimetry Studies of Ammonia, Nitric Acid, and Ammonium Nitrate

DTIC Science & Technology

1979-10-01

50 microns of Hg. Glass ampules containing NH4NO3were filled in the dry box and then flame-sealed under a nitrogen atmosphere. A Karl - Fischer titration...was standardized by potentiometric titration against standard 1 N HCI, For calorimetric measurements, samples were transferred by syringe into weighed... potentiometric titration against standard 1 N NaOH, was 99.6 + 0.2 wt% HNO3. As a measure of tte extent of reaction with the wall oTthe3* calorimeter, HNO3

Amperometric, Bipotentiometric, and Coulometric Titration.

ERIC Educational Resources Information Center

Stock, John T.

1980-01-01

Discusses recent review articles in various kinds of titration. Also discusses new research in apparatus and methodology, acid-base reactions, precipitation and complexing reactions, oxidation-reduction reactions, and nomenclature. Cites 338 references. (CS)

Insulin degludec/insulin aspart once daily in Type 2 diabetes: a comparison of simple or stepwise titration algorithms (BOOST® : SIMPLE USE).

PubMed

Park, S W; Bebakar, W M W; Hernandez, P G; Macura, S; Hersløv, M L; de la Rosa, R

2017-02-01

To compare the efficacy and safety of two titration algorithms for insulin degludec/insulin aspart (IDegAsp) administered once daily with metformin in participants with insulin-naïve Type 2 diabetes mellitus. This open-label, parallel-group, 26-week, multicentre, treat-to-target trial, randomly allocated participants (1:1) to two titration arms. The Simple algorithm titrated IDegAsp twice weekly based on a single pre-breakfast self-monitored plasma glucose (SMPG) measurement. The Stepwise algorithm titrated IDegAsp once weekly based on the lowest of three consecutive pre-breakfast SMPG measurements. In both groups, IDegAsp once daily was titrated to pre-breakfast plasma glucose values of 4.0-5.0 mmol/l. Primary endpoint was change from baseline in HbA 1c (%) after 26 weeks. Change in HbA 1c at Week 26 was IDegAsp Simple -14.6 mmol/mol (-1.3%) (to 52.4 mmol/mol; 6.9%) and IDegAsp Stepwise -11.9 mmol/mol (-1.1%) (to 54.7 mmol/mol; 7.2%). The estimated between-group treatment difference was -1.97 mmol/mol [95% confidence interval (CI) -4.1, 0.2] (-0.2%, 95% CI -0.4, 0.02), confirming the non-inferiority of IDegAsp Simple to IDegAsp Stepwise (non-inferiority limit of ≤ 0.4%). Mean reduction in fasting plasma glucose and 8-point SMPG profiles were similar between groups. Rates of confirmed hypoglycaemia were lower for IDegAsp Stepwise [2.1 per patient years of exposure (PYE)] vs. IDegAsp Simple (3.3 PYE) (estimated rate ratio IDegAsp Simple /IDegAsp Stepwise 1.8; 95% CI 1.1, 2.9). Nocturnal hypoglycaemia rates were similar between groups. No severe hypoglycaemic events were reported. In participants with insulin-naïve Type 2 diabetes mellitus, the IDegAsp Simple titration algorithm improved HbA 1c levels as effectively as a Stepwise titration algorithm. Hypoglycaemia rates were lower in the Stepwise arm. © 2016 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

FecB, a periplasmic ferric-citrate transporter from E. coli, can bind different forms of ferric-citrate as well as a wide variety of metal-free and metal-loaded tricarboxylic acids.

PubMed

Banerjee, Sambuddha; Paul, Subrata; Nguyen, Leonard T; Chu, Byron C H; Vogel, Hans J

2016-01-01

The Escherichia coli Fec system, consisting of an outer membrane receptor (FecA), a periplasmic substrate binding protein (FecB) and an inner membrane permease-ATPase type transporter (FecC/D), plays an important role in the uptake and transport of Fe(3+)-citrate. Although several FecB sequences from various organisms have been reported, there are no biophysical or structural data available for this protein to date. In this work, using isothermal titration calorimetry (ITC), we report for the first time the ability of FecB to bind different species of Fe(3+)-citrate as well as other citrate complexes with trivalent (Ga(3+), Al(3+), Sc(3+) and In(3+)) and a representative divalent metal ion (Mg(2+)) with low μM affinity. Interestingly, ITC experiments with various iron-free di- and tricarboxylic acids show that FecB can bind tricarboxylates with μM affinity but not biologically relevant dicarboxylates. The ability of FecB to bind with metal-free citrate is also observed in (1)H,(15)N HSQC-NMR titration experiments reported here at two different pH values. Further, differential scanning calorimetry (DSC) experiments indicate that the ligand-bound form of FecB has greater thermal stability than ligand-free FecB under all pH and ligand conditions tested, which is consistent with the idea of domain closure subsequent to ligand binding for this type of periplasmic binding proteins.

Undergraduate Analytical Chemistry Experiment: The Determination of Formation Constants for Acetate and Mono-and Dichloroacetate Salts of Primary, Secondary, and Tertiary Methyl-and Ethylamines

ERIC Educational Resources Information Center

D'Amelia, Ronald P.; Chiang, Stephanie; Pollut, Stephanie; Nirode, William F.

2014-01-01

The formation and the hydrolysis of organic salts produced by the titration of a 0.1 M solution of the following amines: methyl-, dimethyl-, trimethyl-, ethyl-, diethyl-, and triethylamine with a 0.1 M solution of acetic, chloroacetic, and dichloracetic acids are studied. The pK[subscript b] of the amine and the pH at the end point were determined…

Metal–organic complexation in the marine environment

PubMed Central

Luther, George W; Rozan, Timothy F; Witter, Amy; Lewis, Brent

2001-01-01

We discuss the voltammetric methods that are used to assess metal–organic complexation in seawater. These consist of titration methods using anodic stripping voltammetry (ASV) and cathodic stripping voltammetry competitive ligand experiments (CSV-CLE). These approaches and a kinetic approach using CSV-CLE give similar information on the amount of excess ligand to metal in a sample and the conditional metal ligand stability constant for the excess ligand bound to the metal. CSV-CLE data using different ligands to measure Fe(III) organic complexes are similar. All these methods give conditional stability constants for which the side reaction coefficient for the metal can be corrected but not that for the ligand. Another approach, pseudovoltammetry, provides information on the actual metal–ligand complex(es) in a sample by doing ASV experiments where the deposition potential is varied more negatively in order to destroy the metal–ligand complex. This latter approach gives concentration information on each actual ligand bound to the metal as well as the thermodynamic stability constant of each complex in solution when compared to known metal–ligand complexes. In this case the side reaction coefficients for the metal and ligand are corrected. Thus, this method may not give identical information to the titration methods because the excess ligand in the sample may not be identical to some of the actual ligands binding the metal in the sample. PMID:16759421

A survey of the year 2007 literature on applications of isothermal titration calorimetry.

PubMed

Bjelić, Sasa; Jelesarov, Ilian

2008-01-01

Elucidation of the energetic principles of binding affinity and specificity is a central task in many branches of current sciences: biology, medicine, pharmacology, chemistry, material sciences, etc. In biomedical research, integral approaches combining structural information with in-solution biophysical data have proved to be a powerful way toward understanding the physical basis of vital cellular phenomena. Isothermal titration calorimetry (ITC) is a valuable experimental tool facilitating quantification of the thermodynamic parameters that characterize recognition processes involving biomacromolecules. The method provides access to all relevant thermodynamic information by performing a few experiments. In particular, ITC experiments allow to by-pass tedious and (rarely precise) procedures aimed at determining the changes in enthalpy and entropy upon binding by van't Hoff analysis. Notwithstanding limitations, ITC has now the reputation of being the "gold standard" and ITC data are widely used to validate theoretical predictions of thermodynamic parameters, as well as to benchmark the results of novel binding assays. In this paper, we discuss several publications from 2007 reporting ITC results. The focus is on applications in biologically oriented fields. We do not intend a comprehensive coverage of all newly accumulated information. Rather, we emphasize work which has captured our attention with originality and far-reaching analysis, or else has provided ideas for expanding the potential of the method. Copyright (c) 2008 John Wiley & Sons, Ltd.

Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

PubMed Central

Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

2010-01-01

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate. PMID:20596083

Double-stranded endonuclease activity in Bacillus halodurans clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas2 protein.

PubMed

Nam, Ki Hyun; Ding, Fran; Haitjema, Charles; Huang, Qingqiu; DeLisa, Matthew P; Ke, Ailong

2012-10-19

The CRISPR (clustered regularly interspaced short palindromic repeats) system is a prokaryotic RNA-based adaptive immune system against extrachromosomal genetic elements. Cas2 is a universally conserved core CRISPR-associated protein required for the acquisition of new spacers for CRISPR adaptation. It was previously characterized as an endoribonuclease with preference for single-stranded (ss)RNA. Here, we show using crystallography, mutagenesis, and isothermal titration calorimetry that the Bacillus halodurans Cas2 (Bha_Cas2) from the subtype I-C/Dvulg CRISPR instead possesses metal-dependent endonuclease activity against double-stranded (ds)DNA. This activity is consistent with its putative function in producing new spacers for insertion into the 5'-end of the CRISPR locus. Mutagenesis and isothermal titration calorimetry studies revealed that a single divalent metal ion (Mg(2+) or Mn(2+)), coordinated by a symmetric Asp pair in the Bha_Cas2 dimer, is involved in the catalysis. We envision that a pH-dependent conformational change switches Cas2 into a metal-binding competent conformation for catalysis. We further propose that the distinct substrate preferences among Cas2 proteins may be determined by the sequence and structure in the β1-α1 loop.

Proof of the quantitative potential of immunofluorescence by mass spectrometry.

PubMed

Toki, Maria I; Cecchi, Fabiola; Hembrough, Todd; Syrigos, Konstantinos N; Rimm, David L

2017-03-01

Protein expression in formalin-fixed, paraffin-embedded patient tissue is routinely measured by Immunohistochemistry (IHC). However, IHC has been shown to be subject to variability in sensitivity, specificity and reproducibility, and is generally, at best, considered semi-quantitative. Mass spectrometry (MS) is considered by many to be the criterion standard for protein measurement, offering high sensitivity, specificity, and objective molecular quantification. Here, we seek to show that quantitative immunofluorescence (QIF) with standardization can achieve quantitative results comparable to MS. Epidermal growth factor receptor (EGFR) was measured by quantitative immunofluorescence in 15 cell lines with a wide range of EGFR expression, using different primary antibody concentrations, including the optimal signal-to-noise concentration after quantitative titration. QIF target measurement was then compared to the absolute EGFR concentration measured by Liquid Tissue-selected reaction monitoring mass spectrometry. The best agreement between the two assays was found when the EGFR primary antibody was used at the optimal signal-to-noise concentration, revealing a strong linear regression (R 2 =0.88). This demonstrates that quantitative optimization of titration by calculation of signal-to-noise ratio allows QIF to be standardized to MS and can therefore be used to assess absolute protein concentration in a linear and reproducible manner.

Binding Isotherms and Time Courses Readily from Magnetic Resonance.

PubMed

Xu, Jia; Van Doren, Steven R

2016-08-16

Evidence is presented that binding isotherms, simple or biphasic, can be extracted directly from noninterpreted, complex 2D NMR spectra using principal component analysis (PCA) to reveal the largest trend(s) across the series. This approach renders peak picking unnecessary for tracking population changes. In 1:1 binding, the first principal component captures the binding isotherm from NMR-detected titrations in fast, slow, and even intermediate and mixed exchange regimes, as illustrated for phospholigand associations with proteins. Although the sigmoidal shifts and line broadening of intermediate exchange distorts binding isotherms constructed conventionally, applying PCA directly to these spectra along with Pareto scaling overcomes the distortion. Applying PCA to time-domain NMR data also yields binding isotherms from titrations in fast or slow exchange. The algorithm readily extracts from magnetic resonance imaging movie time courses such as breathing and heart rate in chest imaging. Similarly, two-step binding processes detected by NMR are easily captured by principal components 1 and 2. PCA obviates the customary focus on specific peaks or regions of images. Applying it directly to a series of complex data will easily delineate binding isotherms, equilibrium shifts, and time courses of reactions or fluctuations.

Structure of the S. aureus PI-specific phospholipase C reveals modulation of active site access by a titratable π-cation latched loop†

PubMed Central

Goldstein, Rebecca; Cheng, Jiongjia; Stec, Boguslaw; Roberts, Mary F.

2012-01-01

Staphylococcus aureus secretes a phosphatidylinositol-specific phospholipase C (PIPLC) as a virulence factor that is unusual in exhibiting higher activity at acidic pH values than other enzymes in this class. We have determined the crystal structure of this enzyme at pH 4.6 and pH 7.5. Under slightly basic conditions, the S. aureus PI-PLC structure closely follows the conformation of other bacterial PI-PLCs. However, when crystallized under acidic conditions, a large section of mobile loop at the αβ-barrel rim in the vicinity of the active site shows ~10 Å shift. This loop displacement at acidic pH is the result of a titratable intramolecular π-cation interaction between His258 and Phe249. This was verified by a structure of the mutant protein H258Y crystallized at pH 4.6, which does not exhibit the large loop shift. The intramolecular π-cation interaction for S. aureus PI-PLC provides an explanation for the activity of the enzyme at acid pH and also suggests how phosphatidylcholine, as a competitor for Phe249, may kinetically activate this enzyme. PMID:22390775

Evaluation of anthocyanins in Aronia melanocarpa/BSA binding by spectroscopic studies.

PubMed

Wei, Jie; Xu, Dexin; Zhang, Xiao; Yang, Jing; Wang, Qiuyu

2018-05-02

The interaction between Anthocyanins in Aronia melanocarpa (AMA) and bovine serum albumin (BSA) were studied in this paper by multispectral technology, such as fluorescence quenching titration, circular dichroism (CD) spectroscopy and Fourier transform infrared spectroscopy (FTIR). The results of the fluorescence titration revealed that AMA could strongly quench the intrinsic fluorescence of BSA by static quenching. The apparent binding constants K SV and number of binding sites n of AMA with BSA were obtained by fluorescence quenching method. The thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS), were calculated to be 18.45 kJ mol -1  > 0 and 149.72 J mol -1  K -1  > 0, respectively, which indicated that the interaction of AMA with BSA was driven mainly by hydrophobic forces. The binding process was a spontaneous process of Gibbs free energy change. Based on Förster's non-radiative energy transfer theory, the distance r between the donor (BSA) and the receptor (AMA) was calculated to be 3.88 nm. Their conformations were analyzed using infrared spectroscopy and CD. The results of multispectral technology showed that the binding of AMA to BSA induced the conformational change of BSA.

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

PubMed

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

2008-11-15

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

Going Beyond, Going Further: Knives, Forks, and Beer Cans as Potentiometric Sensors.

ERIC Educational Resources Information Center

Selig, Walter S.

1985-01-01

Background information, materials needed, and procedures used are provided for potentiometric fluoride, halide, orthophosphate, and sulfate titrations. Typical results obtained are also provided for each type of titration. (JN)

A Titration Technique for Demonstrating a Magma Replenishment Model.

ERIC Educational Resources Information Center

Hodder, A. P. W.

1983-01-01

Conductiometric titrations can be used to simulate subduction-setting volcanism. Suggestions are made as to the use of this technique in teaching volcanic mechanisms and geochemical indications of tectonic settings. (JN)

Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects.

PubMed

Scherz, Michael W; Brossard, Patrick; D'Ambrosio, Daniele; Ipek, Murat; Dingemanse, Jasper

2015-06-01

Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent reduction of circulating lymphocytes upon oral dosing. Previous studies showed that single doses up to 75 mg or multiple doses up to 40 mg once daily are well tolerated, and heart rate (HR) reduction and atrio-ventricular conduction delays upon treatment initiation are reduced by gradual up-titration to the maintenance dose. This single-center, open-label, randomized, multiple-dose, 3-treatment, 3-way crossover study compared the tolerability, safety, pharmacokinetics, cardiodynamics, and effects on lymphocytes of 3 different up-titration regimens of ponesimod in healthy male and female subjects. Up-titration regimens comprised escalating periods of b.i.d. dosing (2.5 or 5 mg) and q.d. dosing (10 or 20 mg or both). After the third up-titration period a variable-duration washout period of 1-3 days was followed by re-challenge with a single 20-mg dose of ponesimod. Adverse events were transient and mild to moderate in intensity, not different between regimens. HR decrease after the first dose was greater than after all subsequent doses, including up-titration doses. Little or no HR change was observed with morning doses of b.i.d. regimens, suggesting that 2.5 and 5 mg b.i.d. are sufficient to sustain cardiac desensitization for the 12-hours dosing interval. © 2015, The American College of Clinical Pharmacology.

Estimating iron and aluminum content of acid mine discharge from a north-central Pennsylvania coal field by use of acidity titration curves

USGS Publications Warehouse

Ott, A.N.

1986-01-01

Determination of acidity provides a value that denotes the quantitative capacity of the sample water to neutralize a strong base to a particular pH. However, much additional information can be obtained from this determination if a titration curve is constructed from recorded data of titrant increments and their corresponding pH values. The curve can be used to identify buffer capabilities, the acidity with respect to any pH value within the curve limit, and, in the case of acid mine drainage from north-central Pennsylvania, the identification and estimation of the concentration of dissolved ferrous iron, ferric iron, and aluminum. Through use of titration curves, a relationship was observed for the acid mine drainage between: (1) the titratable acidity (as milligrams per liter calcium carbonate) to pH 4.0 and the concentration of dissolved ferric iron; and (2) the titratable acidity (as milligrams per liter calcium carbonate) from pH 4.0 to 5.0 and the concentration of dissolved aluminum. The presence of dissolved ferrous iron can be detected by the buffering effect exhibited in the area between pH 5.5 to 7.5. The concentration of ferrous iron is estimated by difference between the concentrations of ferric iron in an oxidized and unoxidized sample. Interferences in any of the titrations from manganese, magnesium, and aluminate, appear to be negligible within the pH range of interest.

Practice parameters for the use of autotitrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: an update for 2007. An American Academy of Sleep Medicine report.

PubMed

Morgenthaler, Timothy I; Aurora, R Nisha; Brown, Terry; Zak, Rochelle; Alessi, Cathy; Boehlecke, Brian; Chesson, Andrew L; Friedman, Leah; Kapur, Vishesh; Maganti, Rama; Owens, Judith; Pancer, Jeffrey; Swick, Todd J

2008-01-01

These practice parameters are an update of the previously published recommendations regarding the use of autotitrating positive airway pressure (APAP) devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome. Continuous positive airway pressure (CPAP) at an effective setting verified by attended polysomnography is a standard treatment for obstructive sleep apnea (OSA). APAP devices change the treatment pressure based on feedback from various patient measures such as airflow, pressure fluctuations, or measures of airway resistance. These devices may aid in the pressure titration process, address possible changes in pressure requirements throughout a given night and from night to night, aid in treatment of OSA when attended CPAP titration has not or cannot be accomplished, or improve patient comfort. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine has reviewed the literature published since the 2002 practice parameter on the use of APAP. Current recommendations follow: (1) APAP devices are not recommended to diagnose OSA; (2) patients with congestive heart failure, patients with significant lung disease such as chronic obstructive pulmonary disease; patients expected to have nocturnal arterial oxyhemoglobin desaturation due to conditions other than OSA (e.g., obesity hypoventilation syndrome); patients who do not snore (either naturally or as a result of palate surgery); and patients who have central sleep apnea syndromes are not currently candidates for APAP titration or treatment; (3) APAP devices are not currently recommended for split-night titration; (4) certain APAP devices may be used during attended titration with polysomnography to identify a single pressure for use with standard CPAP for treatment of moderate to severe OSA; (5) certain APAP devices may be initiated and used in the self-adjusting mode for unattended treatment of patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (6) certain APAP devices may be used in an unattended way to determine a fixed CPAP treatment pressure for patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (7) patients being treated with fixed CPAP on the basis of APAP titration or being treated with APAP must have close clinical follow-up to determine treatment effectiveness and safety; and (8) a reevaluation and, if necessary, a standard attended CPAP titration should be performed if symptoms do not resolve or the APAP treatment otherwise appears to lack efficacy.

Developing a multipoint titration method with a variable dose implementation for anaerobic digestion monitoring.

PubMed

Salonen, K; Leisola, M; Eerikäinen, T

2009-01-01

Determination of metabolites from an anaerobic digester with an acid base titration is considered as superior method for many reasons. This paper describes a practical at line compatible multipoint titration method. The titration procedure was improved by speed and data quality. A simple and novel control algorithm for estimating a variable titrant dose was derived for this purpose. This non-linear PI-controller like algorithm does not require any preliminary information from sample. Performance of this controller is superior compared to traditional linear PI-controllers. In addition, simplification for presenting polyprotic acids as a sum of multiple monoprotic acids is introduced along with a mathematical error examination. A method for inclusion of the ionic strength effect with stepwise iteration is shown. The titration model is presented with matrix notations enabling simple computation of all concentration estimates. All methods and algorithms are illustrated in the experimental part. A linear correlation better than 0.999 was obtained for both acetate and phosphate used as model compounds with slopes of 0.98 and 1.00 and average standard deviations of 0.6% and 0.8%, respectively. Furthermore, insensitivity of the presented method for overlapping buffer capacity curves was shown.

PubMed Central

Derouin, F.; Garin, Y. J.; Buffard, C.; Berthelot, F.; Petithory, J. C.

1994-01-01

A collaborative study conducted by the French National Agency for Quality Control in Parasitology (CNQP) and various manufacturers of ELISA kits, represented by the Association of Laboratory Reagent Manufacturers (SFRL) compared the toxoplasmosis IgG antibody titres obtained with different ELISA-IgG kits and determined the relationships between the titres obtained by these techniques and the titre defined in international units (IU). Fifty-one serum samples with toxoplasmosis antibody titres ranging from 0 to 900 IU were tested in two successive studies with 16 ELISA-IgG kits. For the negative sera, false-positive reactions were observed with one kit. For the positive sera, the titres observed in ELISA were generally higher than those expressed in IU. Above 250 IU, the very wide variability of the titres found with the different ELISA kits renders any comparative analysis impossible. For titres below 250 IU, the results are sufficiently homogeneous to permit the use of regression analysis to study how the results for each ELISA kit compare with the mean results for the other kits. The slope of the line of regression shows a tendency to over-titration or under-titration compared with the results of the other manufacturers; the ordinate at the origin reflects the positivity threshold of the reaction and can be used to assess the risk of a lack of sensitivity (high threshold) or of specificity (threshold too low). On the whole, the trends revealed for a given manufacturer are constant from one study to the other. Within this range of titres, regression analysis also reveals the general tendency of ELISA kits to overestimate the titres by comparison with immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8205645

9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

Code of Federal Regulations, 2011 CFR

2011-01-01

... challenged intraperitoneally with botulinum Type C toxin which has been titrated in mice to provide for a 104.0 mouse MLD dose. The titration technique shall include inoculation of the mice intraperitoneally...

A multi writable thiophene-based selective and reversible chromogenic fluoride probe with dual -NH functionality

NASA Astrophysics Data System (ADS)

Vishwakarma, Siddharth; Kumar, Ajit; Pandey, Abha; Upadhyay, K. K.

2017-01-01

A chromogenic fluoride probe bearing bis imine groups having dual -NH functionality (BSB) has been designed, synthesised and structurally characterized by its single crystal X-ray diffraction studies. The BSB could visually and spectroscopically recognise F- with high selectivity over other anions by exhibiting intense chromogenic response (from colourless to red) for F- in acetonitrile solution. The UV-visible titration and 1H NMR titration experiments indicated that the observed changes occur via a combined process including hydrogen bonding and deprotonation between the BSB and F-. Moreover theoretical calculations at the Density Functional Theory (DFT) level shed further light upon probe design strategy and the nature of interactions between BSB and F-. The limit of detection and binding constant of BSB towards F- were found to be 6.9 × 10- 7 M and 1.42 ± 0.069 × 108 M- 2 respectively. Finally, by using F- and H+ as chemical inputs and the absorbance as output, a INHIBIT logic gate was constructed, which exhibits "Multi-write" ability without obvious degradation in its optical output.

Structural changes in calcium-binding allergens: use of circular dichroism to study binding characteristics.

PubMed

Hebenstreit, D; Ferreira, F

2005-09-01

Several studies showed that calcium-binding proteins have a fixed place in the spectrum of allergenic substances. Often the binding of a calcium ion induces conformational changes and affects immunoglobulin E-binding to the allergen. Hence, the quantitative characterization of the binding to calcium is of importance to understand both the biologic and allergenic activity of these proteins. In the present study we describe a procedure for determining the stoichiometry and dissociation constant (K(D)) of calcium-binding allergens using circular dichroism (CD) techniques. For the experiments, we used recombinant Bet v 4, a two EF-hand allergen from birch pollen. Solutions of Bet v 4 were titrated with calcium and the change in molar ellipticity at 222 nm was monitored with a CD spectropolarimeter. The determination of the binding stoichiometry as well as of the K(D) for one EF-hand (4 microM) demonstrated the applicability of the method. CD-monitored calcium-titration of protein solutions represents a fast and easy method for determining the binding characteristics of calcium-binding allergens.

NMR and MD Investigations of Human Galectin-1/Oligosaccharide Complexes

PubMed Central

Meynier, Christophe; Feracci, Mikael; Espeli, Marion; Chaspoul, Florence; Gallice, Philippe; Schiff, Claudine; Guerlesquin, Françoise; Roche, Philippe

2009-01-01

Abstract The specific recognition of carbohydrates by lectins plays a major role in many cellular processes. Galectin-1 belongs to a family of 15 structurally related β-galactoside binding proteins that are able to control a variety of cellular events, including cell cycle regulation, adhesion, proliferation, and apoptosis. The three-dimensional structure of galectin-1 has been solved by x-ray crystallography in the free form and in complex with various carbohydrate ligands. In this work, we used a combination of two-dimensional NMR titration experiments and molecular-dynamics simulations with explicit solvent to study the mode of interaction between human galectin-1 and five galactose-containing ligands. Isothermal titration calorimetry measurements were performed to determine their affinities for galectin-1. The contribution of the different hexopyranose units in the protein-carbohydrate interaction was given particular consideration. Although the galactose moiety of each oligosaccharide is necessary for binding, it is not sufficient by itself. The nature of both the reducing sugar in the disaccharide and the interglycosidic linkage play essential roles in the binding to human galectin-1. PMID:20006954

Tools for building a comprehensive modeling system for virtual screening under real biological conditions: The Computational Titration algorithm.

PubMed

Kellogg, Glen E; Fornabaio, Micaela; Chen, Deliang L; Abraham, Donald J; Spyrakis, Francesca; Cozzini, Pietro; Mozzarelli, Andrea

2006-05-01

Computational tools utilizing a unique empirical modeling system based on the hydrophobic effect and the measurement of logP(o/w) (the partition coefficient for solvent transfer between 1-octanol and water) are described. The associated force field, Hydropathic INTeractions (HINT), contains much rich information about non-covalent interactions in the biological environment because of its basis in an experiment that measures interactions in solution. HINT is shown to be the core of an evolving virtual screening system that is capable of taking into account a number of factors often ignored such as entropy, effects of solvent molecules at the active site, and the ionization states of acidic and basic residues and ligand functional groups. The outline of a comprehensive modeling system for virtual screening that incorporates these features is described. In addition, a detailed description of the Computational Titration algorithm is provided. As an example, three complexes of dihydrofolate reductase (DHFR) are analyzed with our system and these results are compared with the experimental free energies of binding.

Determination of sulfur compounds in hydrotreated transformer base oil by potentiometric titration.

PubMed

Chao, Qiu; Sheng, Han; Cheng, Xingguo; Ren, Tianhui

2005-06-01

A method was developed to analyze the distribution of sulfur compounds in model sulfur compounds by potentiometric titration, and applied to analyze hydrotreated transformer base oil. Model thioethers were oxidized to corresponding sulfoxides by tetrabutylammonium periodate and sodium metaperiodate, respectively, and the sulfoxides were titrated by perchloric acid titrant in acetic anhydride. The contents of aliphatic thioethers and total thioethers were then determined from that of sulfoxides in solution. The method was applied to determine the organic sulfur compounds in hydrotreated transformer base oil.

Thermometric titrimetry Studies of the cerium(IV) oxidation of alpha-mercaptocarboxylic acids.

PubMed

Alexander, W A; Mash, C J; McAuley, A

1969-04-01

The cerium(IV) oxidation of thioglycollic, thiolactic and thiomalic acids has been examined by thermometric titration. The titration curves indicate stoichiometries of more than 1 mole of cerium(IV) per mole of alpha-thiol, suggesting possible side-reactions. In the presence of methyl acrylate, however, the expected ratio is observed. The overall heat of each reaction has been derived. Only with a titration method of this kind where allowance can be made for side-reactions can the heats of reaction for these systems be measured.

A Colorimetric and Luminescent Dual-Modal Assay for Cu(II) Ion Detection Using an Iridium(III) Complex

PubMed Central

Ma, Dik-Lung; He, Hong-Zhang; Chan, Daniel Shiu-Hin; Wong, Chun-Yuen; Leung, Chung-Hang

2014-01-01

A novel iridium(III) complex-based chemosensor bearing the 5,6-bis(salicylideneimino)-1,10-phenanthroline ligand receptor was developed, which exhibited a highly sensitive and selective color change from colorless to yellow and a visible turn-off luminescence response upon the addition of Cu(II) ions. The interactions of this iridium(III) complex with Cu2+ ions and thirteen other cations have been investigated by UV-Vis absorption titration, emission titration, and 1H NMR titration. PMID:24927177

Practice Parameters for the Use of Autotitrating Continuous Positive Airway Pressure Devices for Titrating Pressures and Treating Adult Patients with Obstructive Sleep Apnea Syndrome: An Update for 2007

PubMed Central

Morgenthaler, Timothy I.; Aurora, R. Nisha; Brown, Terry; Zak, Rochelle; Alessi, Cathy; Boehlecke, Brian; Chesson, Andrew L.; Friedman, Leah; Kapur, Vishesh; Maganti, Rama; Owens, Judith; Pancer, Jeffrey; Swick, Todd J.

2008-01-01

These practice parameters are an update of the previously published recommendations regarding the use of autotitrating positive airway pressure (APAP) devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome. Continuous positive airway pressure (CPAP) at an effective setting verified by attended polysomnography is a standard treatment for obstructive sleep apnea (OSA). APAP devices change the treatment pressure based on feedback from various patient measures such as airflow, pressure fluctuations, or measures of airway resistance. These devices may aid in the pressure titration process, address possible changes in pressure requirements throughout a given night and from night to night, aid in treatment of OSA when attended CPAP titration has not or cannot be accomplished, or improve patient comfort. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine has reviewed the literature published since the 2002 practice parameter on the use of APAP. Current recommendations follow: (1) APAP devices are not recommended to diagnose OSA; (2) patients with congestive heart failure, patients with significant lung disease such as chronic obstructive pulmonary disease; patients expected to have nocturnal arterial oxyhemoglobin desaturation due to conditions other than OSA (e.g., obesity hypoventilation syndrome); patients who do not snore (either naturally or as a result of palate surgery); and patients who have central sleep apnea syndromes are not currently candidates for APAP titration or treatment; (3) APAP devices are not currently recommended for split-night titration; (4) certain APAP devices may be used during attended titration with polysomnography to identify a single pressure for use with standard CPAP for treatment of moderate to severe OSA; (5) certain APAP devices may be initiated and used in the self-adjusting mode for unattended treatment of patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (6) certain APAP devices may be used in an unattended way to determine a fixed CPAP treatment pressure for patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (7) patients being treated with fixed CPAP on the basis of APAP titration or being treated with APAP must have close clinical follow-up to determine treatment effectiveness and safety; and (8) a reevaluation and, if necessary, a standard attended CPAP titration should be performed if symptoms do not resolve or the APAP treatment otherwise appears to lack efficacy. Citation: Morgenthaler TI; Aurora RN; Brown T; Zak R; Alessi C; Boehlecke B; Chesson AL; Friedman L; Kapur V; Maganti R; Owens J; Pancer J; Swick TJ; Standards of Practice Committee of the AASM. Practice parameters for the use of autotitrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: An update for 2007. SLEEP 2008;31(1):141-147. PMID:18220088

A comparison between simplified and intensive dose-titration algorithms using AIR inhaled insulin for insulin-naive patients with type 2 diabetes in a randomized noninferiority trial.

PubMed

Mathieu, C; Cuddihy, R; Arakaki, R F; Belin, R M; Planquois, J-M; Lyons, J N; Heilmann, C R

2009-09-01

Insulin initiation and optimization is a challenge for patients with type 2 diabetes. Our objective was to determine whether safety and efficacy of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) using a simplified regimen was noninferior to an intensive regimen. This was an open-label, randomized study in insulin-naive adults not optimally controlled by oral antihyperglycemic medications. Simplified titration included a 6 U per meal AIR insulin starting dose. Individual doses were adjusted at mealtime in 2-U increments from the previous day's four-point self-monitored blood glucose (SMBG) (total < or =6 U). Starting Air insulin doses for intensive titration were based on fasting blood glucose, gender, height, and weight. Patients conducted four-point SMBG daily for the study duration. Insulin doses were titrated based on the previous 3 days' mean SMBG (total < or =8 U). End point hemoglobin A1C (A1C) was 7.07 +/- 0.09% and 6.87 +/- 0.09% for simplified (n = 178) and intensive (n = 180) algorithms, respectively. Noninferiority between algorithms was not established. The fasting blood glucose (least squares mean +/- standard error) values for the simplified (137.27 +/- 3.42 mg/dL) and intensive (133.13 +/- 3.42 mg/dL) algorithms were comparable. Safety profiles were comparable. The hypoglycemic rate at 4, 8, 12, and 24 weeks was higher in patients receiving intensive titration (all P < .0001). The nocturnal hypoglycemic rate for patients receiving intensive titration was higher than for those receiving simplified titration at 8 (P < 0.015) and 12 weeks (P < 0.001). Noninferiority between the algorithms, as measured by A1C, was not demonstrated. This finding re-emphasizes the difficulty of identifying optimal, simplified insulin regimens for patients.

Number of independent parameters in the potentiometric titration of humic substances.

PubMed

Lenoir, Thomas; Manceau, Alain

2010-03-16

With the advent of high-precision automatic titrators operating in pH stat mode, measuring the mass balance of protons in solid-solution mixtures against the pH of natural and synthetic polyelectrolytes is now routine. However, titration curves of complex molecules typically lack obvious inflection points, which complicates their analysis despite the high-precision measurements. The calculation of site densities and median proton affinity constants (pK) from such data can lead to considerable covariance between fit parameters. Knowing the number of independent parameters that can be freely varied during the least-squares minimization of a model fit to titration data is necessary to improve the model's applicability. This number was calculated for natural organic matter by applying principal component analysis (PCA) to a reference data set of 47 independent titration curves from fulvic and humic acids measured at I = 0.1 M. The complete data set was reconstructed statistically from pH 3.5 to 9.8 with only six parameters, compared to seven or eight generally adjusted with common semi-empirical speciation models for organic matter, and explains correlations that occur with the higher number of parameters. Existing proton-binding models are not necessarily overparametrized, but instead titration data lack the sensitivity needed to quantify the full set of binding properties of humic materials. Model-independent conditional pK values can be obtained directly from the derivative of titration data, and this approach is the most conservative. The apparent proton-binding constants of the 23 fulvic acids (FA) and 24 humic acids (HA) derived from a high-quality polynomial parametrization of the data set are pK(H,COOH)(FA) = 4.18 +/- 0.21, pK(H,Ph-OH)(FA) = 9.29 +/- 0.33, pK(H,COOH)(HA) = 4.49 +/- 0.18, and pK(H,Ph-OH)(HA) = 9.29 +/- 0.38. Their values at other ionic strengths are more reliably calculated with the empirical Davies equation than any existing model fit.

A geochemical module for "AMDTreat" to compute caustic quantity, effluent quantity, and sludge volume

USGS Publications Warehouse

Cravotta, Charles A.; Parkhurst, David L.; Means, Brent P; McKenzie, Bob; Morris, Harry; Arthur, Bill

2010-01-01

Treatment with caustic chemicals typically is used to increase pH and decrease concentrations of dissolved aluminum, iron, and/or manganese in largevolume, metal-laden discharges from active coal mines. Generally, aluminum and iron can be removed effectively at near-neutral pH (6 to 8), whereas active manganese removal requires treatment to alkaline pH (~10). The treatment cost depends on the specific chemical used (NaOH, CaO, Ca(OH)2, Na2CO3, or NH3) and increases with the quantities of chemical added and sludge produced. The pH and metals concentrations do not change linearly with the amount of chemical added. Consequently, the amount of caustic chemical needed to achieve a target pH and the corresponding effluent composition and sludge volume can not be accurately determined without empirical titration data or the application of geochemical models to simulate the titration of the discharge water with caustic chemical(s). The AMDTreat computer program (http://amd.osmre.gov/ ) is widely used to compute costs for treatment of coal-mine drainage. Although AMDTreat can use results of empirical titration with industrial grade caustic chemicals to compute chemical costs for treatment of net-acidic or net-alkaline mine drainage, such data are rarely available. To improve the capability of AMDTreat to estimate (1) the quantity and cost of caustic chemicals to attain a target pH, (2) the concentrations of dissolved metals in treated effluent, and (3) the volume of sludge produced by the treatment, a titration simulation is being developed using the geochemical program PHREEQC (wwwbrr.cr.usgs.gov/projects/GWC_coupled/phreeqc/) that will be coupled as a module to AMDTreat. The simulated titration results can be compared with or used in place of empirical titration data to estimate chemical quantities and costs. This paper describes the development, evaluation, and potential utilization of the PHREEQC titration module for AMDTreat.

Equivalence of Nasal and Oronasal Masks during Initial CPAP Titration for Obstructive Sleep Apnea Syndrome

PubMed Central

Teo, Ming; Amis, Terence; Lee, Sharon; Falland, Karina; Lambert, Stephen; Wheatley, John

2011-01-01

Study Objective: Continuous positive airway pressure (CPAP) titration studies are commonly performed using a nasal mask but some patients may prefer a full-face or oronasal mask. There is little evidence regarding the equivalence of different mask interfaces used to initiate treatment. We hypothesized that oronasal breathing when using an oronasal mask increases upper airway collapsibility and that a higher pressure may be required to maintain airway patency. We also assessed patient preferences for the 2 mask interfaces. Design: Prospective, randomized, cross-over design with 2 consecutive CPAP titration nights. Setting: Accredited laboratory in a university hospital. Patients or Participants: Twenty-four treatment-naive subjects with obstructive sleep apnea syndrome and respiratory disturbance index of greater than 15 events per hour. Interventions: CPAP titration was performed using an auto-titrating machine with randomization to a nasal or oronasal mask, followed by a second titration night using the alternate mask style. Measurements and Results: There was no significant difference in the mean pressures determined between nasal and oronasal masks, although 43% of subjects had nasal-to-oronasal mask-pressure differences of 2 cm H2O or more. Residual respiratory events, arousals, and measured leak were all greater with the oronasal mask. Seventy-nine percent of subjects preferred the nasal mask. Conclusions: Patients with obstructive sleep apnea syndrome can generally switch between nasal and oronasal masks without changing machine pressure, although there are individual differences that may be clinically significant. Measured leak is greater with the oronasal mask. Most patients with obstructive sleep apnea syndrome prefer a nasal mask as the interface for initiation of CPAP. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN: ACTRN12611000243910. URL: http://www.ANZCTR.org.au/ACTRN12611000243910.aspx Citation: Teo M; Amis T; Lee S; Falland K; Lambert S; Wheatley J. Equivalence of nasal and oronasal masks during initial CPAP titration for obstructive sleep apnea syndrome. SLEEP 2011;34(7):951-955. PMID:21731145

Patient-led versus physician-led titration of insulin glargine in patients with uncontrolled type 2 diabetes: a randomized multinational ATLAS study.

PubMed

Garg, Satish K; Admane, Karim; Freemantle, Nick; Odawara, Masato; Pan, Chang-Yu; Misra, Anoop; Jarek-Martynowa, Iwona R; Abbas-Raza, Syed; Mirasol, Roberto C; Perfetti, Riccardo

2015-02-01

Self-adjustment of insulin dose is commonly practiced in Western patients with type 2 diabetes but is usually not performed in Asian patients. This multinational, 24-week, randomized study compared patient-led with physician-led titration of once-daily insulin glargine in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering agents. Patient-led (n = 275) or physician-led (n = 277) subjects followed the same dose-titration algorithm guided by self-monitored fasting blood glucose (FBG; target, 110 mg/dL [6.1 mmol/L]). The primary endpoint was change in mean glycated hemoglobin (HbA1c) at week 24 in the patient-led versus physician-led titration groups. Patient-led titration resulted in a significantly higher drop in HbA1c value at 24 weeks when compared with physician-led titration (-1.40% vs. -1.25%; mean difference, -0.15; 95% confidence interval, -0.29 to 0.00; P = .043). Mean decrease in FBG was greatest in the patient-led group (-2.85 mmol/L vs. -2.48 mmol/L; P = .001). The improvements in HbA1c and FBG were consistent across countries, with similar improvements in treatment satisfaction in both groups. Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2 units; P<.001). Target HbA1c of <7.0% without severe hypoglycemia was achieved in 40.0% and 32.9% in the patient-led and physician-led groups, respectively (P = .086). Severe hypoglycemia was not different in the 2 groups (0.7%), with an increase in nocturnal and symptomatic hypoglycemia in the patient-led arm. Patient-led insulin glargine titration achieved near-target blood glucose levels in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering drugs, demonstrating that Asian patients can self-uptitrate insulin dose effectively when guided.

Effectiveness of a management program for outpatient clinic or remote titration of beta-blockers in CRT patients: The RESTORE study.

PubMed

D'Onofrio, Antonio; Palmisano, Pietro; Rapacciuolo, Antonio; Ammendola, Ernesto; Calò, Leonardo; Ruocco, Antonio; Bianchi, Valter; Maresca, Fabio; Del Giorno, Giuseppe; Martino, Annamaria; Mauro, Ciro; Campari, Monica; Valsecchi, Sergio; Accogli, Michele

2017-06-01

Many patients fail to receive β-blockers before cardiac resynchronization therapy defibrillator (CRT-D) implantation, or receive them at a suboptimal dose, and require optimization after implantation. We assessed the effectiveness of a structured program for β-blocker titration in CRT-D patients followed up by means of conventional in-clinic visits or remote monitoring. 130 patients undergoing CRT implantation and treated according to the standard practice of the centers were included as a control group. A second group of 124 CRT-D candidates (Study Group) underwent up-titration visits every 2weeks after implantation (target dose: 10mg/day of bisoprolol or 50mg/day of carvedilol). In the Study Group, remote monitoring was undertaken in 66 patients, who received additional equipment for daily transmission of weight and blood pressure data, and scheduled titration telephone calls. In the Control Group, the maximal dose of β-blockers was being administered to 12 (9%) patients on implantation and 21 (16%) on 6-month follow-up examination (p>0.05). In the Study Group, 25 (20%) patients were receiving the maximal dose of β-blockers on implantation and 72 (58%) on follow-up examination (p<0.001). The 66 Study Group patients on remote monitoring underwent fewer in-clinic visits (p=0.034). Of these, 50 (76%) were on the maximal dose after remote up-titration (versus 38% of patients followed up conventionally, p<0.001). The decrease in left ventricular end-systolic volume was larger in the Study Group (p=0.040). The program for β-blocker up-titration increased the number of patients reaching the target dose and improved the response to the therapy. The use of remote monitoring and daily transfer of weight and blood pressure data facilitated β-blocker titration. URL: http://clinicaltrials.gov/ Identifier: NCT02173028. Copyright © 2017. Published by Elsevier B.V.

A comparison of sports and energy drinks--Physiochemical properties and enamel dissolution.

PubMed

Jain, Poonam; Hall-May, Emily; Golabek, Kristi; Agustin, Ma Zenia

2012-01-01

The consumption of sports and energy drinks by children and adolescents has increased at an alarming rate in recent years. It is essential for dental professionals to be informed about the physiochemical properties of these drinks and their effects on enamel. The present study measured the fluoride levels, pH, and titratable acidity of multiple popular, commercially available brands of sports and energy drinks. Enamel dissolution was measured as weight loss using an in vitro multiple exposure model consisting of repeated short exposures to these drinks, alternating with exposure to artificial saliva. The relationship between enamel dissolution and fluoride levels, pH, and titratable acidity was also examined. There was a statistically significant difference between the fluoride levels (p = 0.034) and pH (p = 0.04) of the sports and energy drinks studied. The titratable acidity of energy drinks (11.78) was found to be significantly higher than that of sports drinks (3.58) (p < 0.001). Five of the energy drinks (Red Bull Sugar Free, Monster Assault, Von Dutch, Rockstar, and 5-Hour Energy) were found to have the highest titratable acidity values among the brands studied. Enamel weight loss after exposure to energy drinks was significantly higher than it was after exposure to sports drinks. The effect of titratable acidity on enamel weight loss was found to vary inversely with the pH of the drinks. The findings indicated that energy drinks have significantly higher titratable acidity and enamel dissolution associated with them than sports drinks. Enamel weight loss after exposure to energy drinks was more than two times higher than it was after exposure to sports drinks. Titratable acidity is a significant predictor of enamel dissolution, and its effect on enamel weight loss varies inversely with the pH of the drink. The data from the current study can be used to educate patients about the differences between sports and energy drinks and the effects of these drinks on tooth enamel.

A Pediatric Intensive Care Unit Bedside Computer Clinical Decision Support Protocol for Hyperglycemia Is Feasible, Safe and Offers Advantages

PubMed Central

Lanspa, Michael J.; Wilson, Emily L.; Sward, Katherine A.; Jephson, Al; Larsen, Gitte Y.; Morris, Alan H.

2017-01-01

Abstract Background: Computer clinical decision support (CDS) systems are uncommon in the pediatric intensive care unit (PICU), despite evidence suggesting they improve outcomes in adult ICUs. We reasoned that a bedside CDS protocol for intravenous insulin titration, eProtocol-insulin, would be feasible and safe in critically ill children. Methods: We retrospectively reviewed data from non-diabetic children admitted to the PICU with blood glucose (BG) ≥140 mg/dL who were managed with intravenous insulin by either unaided clinician titration or eProtocol-insulin. Primary outcomes were BG measurements in target range (80–110 mg/dL) and severe hypoglycemia (BG ≤40 mg/dL); secondary outcomes were 60-day mortality and PICU length of stay. We assessed bedside nurse satisfaction with the eProtocol-insulin protocol by using a 5-point Likert scale and measured clinician compliance with eProtocol-insulin recommendations. Results: Over 5 years, 69 children were titrated with eProtocol-insulin versus 104 by unaided clinicians. eProtocol-insulin achieved target range more frequently than clinician titration (41% vs. 32%, P < 0.001). Severe hypoglycemia was uncommon in both groups (4.3% of patients in eProtocol-insulin, 8.7% in clinician titration, P = 0.37). There were no differences in mean time to BG target or median BG between the groups. Mortality was 23% in both groups. Clinician compliance with eProtocol-insulin recommendations was 89%. Nurses believed that eProtocol-insulin was easy to understand and safer than clinician titration. Conclusions: eProtocol-insulin is safe for titration of intravenous insulin in critically ill children. Clinical research protocols and quality improvement initiatives aimed at optimizing BG control should utilize detailed computer protocols that enable replicable clinician decisions. PMID:28248127

Effect of neuromonitor-guided titrated care on brain tissue hypoxia after opioid overdose cardiac arrest.

PubMed

Elmer, Jonathan; Flickinger, Katharyn L; Anderson, Maighdlin W; Koller, Allison C; Sundermann, Matthew L; Dezfulian, Cameron; Okonkwo, David O; Shutter, Lori A; Salcido, David D; Callaway, Clifton W; Menegazzi, James J

2018-04-18

Brain tissue hypoxia may contribute to preventable secondary brain injury after cardiac arrest. We developed a porcine model of opioid overdose cardiac arrest and post-arrest care including invasive, multimodal neurological monitoring of regional brain physiology. We hypothesized brain tissue hypoxia is common with usual post-arrest care and can be prevented by modifying mean arterial pressure (MAP) and arterial oxygen concentration (PaO 2 ). We induced opioid overdose and cardiac arrest in sixteen swine, attempted resuscitation after 9 min of apnea, and randomized resuscitated animals to three alternating 6-h blocks of standard or titrated care. We invasively monitored physiological parameters including brain tissue oxygen (PbtO 2 ). During standard care blocks, we maintained MAP > 65 mmHg and oxygen saturation 94-98%. During titrated care, we targeted PbtO2 > 20 mmHg. Overall, 10 animals (63%) achieved ROSC after a median of 12.4 min (range 10.8-21.5 min). PbtO 2 was higher during titrated care than standard care blocks (unadjusted β = 0.60, 95% confidence interval (CI) 0.42-0.78, P < 0.001). In an adjusted model controlling for MAP, vasopressors, sedation, and block sequence, PbtO 2 remained higher during titrated care (adjusted β = 0.75, 95%CI 0.43-1.06, P < 0.001). At three predetermined thresholds, brain tissue hypoxia was significantly less common during titrated care blocks (44 vs 2% of the block duration spent below 20 mmHg, P < 0.001; 21 vs 0% below 15 mmHg, P < 0.001; and, 7 vs 0% below 10 mmHg, P = .01). In this model of opioid overdose cardiac arrest, brain tissue hypoxia is common and treatable. Further work will elucidate best strategies and impact of titrated care on functional outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Amperometric, Bipotentiometric, and Coulometric Titration.

ERIC Educational Resources Information Center

Stock, John T.

1984-01-01

Reviews literature on amperometric, bipotentiometric, and coulometric titration methods examining: apparatus and methodology; acid-base reactions; precipitation and complexing reactions (considering methods involving silver, mercury, EDTA or analogous reagents, and other organic compounds); and oxidation-reduction reactions (considering methods…

Thermometric titration of thorium with EDTA in the presence of large excess of neutral sodium salts.

PubMed

Doi, K

1980-11-01

The thermometric titration of Th(IV) in the presence of neutral sodium salts, sulphuric acid or acetic acid with EDTA has been studied. The effect of each on the observed heat values for the titration is discussed. For sodium perchlorate media, DeltaH values of -9 and -21 kJ/mole have been estimated for the formation of the Th(IV)-EDTA chelate at mu --> 0 and mu = 0.5 (NaClO(4)), respectively. The -DeltaH values increase steadily with increase in concentration of sodium perchlorate up to at least 3M. For the titration of Th(IV) in the presence of a large excess of sodium nitrate the use of sodium iodide as a masking reagent has been examined: large amounts of Bi and Cu(II) are masked and a masking effect is observed for small amounts of Ni.

Increasing the Detection Limit of the Parkinson Disorder through a Specific Surface Chemistry Applied onto Inner Surface of the Titration Well.

PubMed

Mille, Caroline; Debarnot, Dominique; Zorzi, Willy; El Moualij, Benaïssa; Coudreuse, Arnaud; Legeay, Gilbert; Quadrio, Isabelle; Perret-Liaudet, Armand; Poncin-Epaillard, Fabienne

2012-04-18

The main objective of this paper was to illustrate the enhancement of the sensitivity of ELISA titration for neurodegenerative proteins by reducing nonspecific adsorptions that could lead to false positives. This goal was obtained thanks to the association of plasma and wet chemistries applied to the inner surface of the titration well. The polypropylene surface was plasma-activated and then, dip-coated with different amphiphilic molecules. These molecules have more or less long hydrocarbon chains and may be charged. The modified surfaces were characterized in terms of hydrophilic-phobic character, surface chemical groups and topography. Finally, the coated wells were tested during the ELISA titration of the specific antibody capture of the α-synuclein protein. The highest sensitivity is obtained with polar (Θ = 35°), negatively charged and smooth inner surface.

Increasing the Detection Limit of the Parkinson Disorder through a Specific Surface Chemistry Applied onto Inner Surface of the Titration Well

PubMed Central

Mille, Caroline; Debarnot, Dominique; Zorzi, Willy; Moualij, Benaïssa El; Coudreuse, Arnaud; Legeay, Gilbert; Quadrio, Isabelle; Perret-Liaudet, Armand; Poncin-Epaillard, Fabienne

2012-01-01

The main objective of this paper was to illustrate the enhancement of the sensitivity of ELISA titration for neurodegenerative proteins by reducing nonspecific adsorptions that could lead to false positives. This goal was obtained thanks to the association of plasma and wet chemistries applied to the inner surface of the titration well. The polypropylene surface was plasma-activated and then, dip-coated with different amphiphilic molecules. These molecules have more or less long hydrocarbon chains and may be charged. The modified surfaces were characterized in terms of hydrophilic—phobic character, surface chemical groups and topography. Finally, the coated wells were tested during the ELISA titration of the specific antibody capture of the α-synuclein protein. The highest sensitivity is obtained with polar (Θ = 35°), negatively charged and smooth inner surface. PMID:24955533

Titrimetric and photometric methods for determination of hypochlorite in commercial bleaches.

PubMed

Jonnalagadda, Sreekanth B; Gengan, Prabhashini

2010-01-01

Two methods, simple titration and photometric methods for determination of hypochlorite are developed, based its reaction with hydrogen peroxide and titration of the residual peroxide by acidic permanganate. In the titration method, the residual hydrogen peroxide is estimated by titration with standard permanganate solution to estimate the hypochlorite concentration. The photometric method is devised to measure the concentration of remaining permanganate, after the reaction with residual hydrogen peroxide. It employs 4 ranges of calibration curves to enable the determination of hypochlorite accurately. The new photometric method measures hypochlorite in the range 1.90 x 10(-3) to 1.90 x 10(-2) M, with high accuracy and with low variance. The concentrations of hypochlorite in diverse commercial bleach samples and in seawater which is enriched with hypochlorite were estimated using the proposed method and compared with the arsenite method. The statistical analysis validates the superiority of the proposed method.

Studies of cellulose surfaces by titration and ESCA

NASA Astrophysics Data System (ADS)

Stenius, Per; Laine, Janne

1994-01-01

The surface properties of unbleached kraft pulp fibers of varying lignin content prepared by digestion with different amounts of excess alkali have been investigated using polyelectrolyte titration, potentiometric titration and ESCA. The surfaces contain two different acidic groups that dissociate completely above pH 7.5, one with pK ≈ 3.6 and one with pK ≈ 5.7. The amount of the latter group correlates directly with the amount of lignin in the pulp. The ESCA analysis indicates that the relative amount of carboxylic groups and alkyl carbon in the surface decreases as the lignin content decreases and also that material with high alkyl carbon content is enriched in the outermost surface of the cellulose. Thus, a combination of ESCA analysis and high-precision titrations is able to yield a very detailed picture of the effect of digestion conditions on surface properties of cellulose fibers of direct relevance to paper properties.

Determination of sulphite in wine by coulometric titration.

PubMed

Lowinsohn, D; Bertotti, M

2001-09-01

A method for the determination of both free and bound S(IV) in white wine samples by coulometric titration with electrogenerated iodine is described, the S(IV) speciation being performed by extracting SO2 from samples acidified wiith hydrochloric acid. Titrations of samples treated with NaOH led to the total S(IV) concentration, the results being in agreement with the ones obtained by the distillation procedure as well as by using the classical Monier-Williams method. An average recovery of 97% was obtained for samples spiked with S(IV) in the range 0.4-1.2 mM, which demonstrated the validity of the proposed procedure. The repeatability was 1.3% and the limit of detection was estimated as 0.01 mM. Results from direct titrations of wine added to the electrochemical cell are reported, which give indications of the stability of adducts towards the reaction with iodine.

Phosphorus Imaging as a Tool for Studying the pH Metabolism in Living Insects

NASA Astrophysics Data System (ADS)

Skibbe, U.; Christeller, J. T.; Eccles, C. D.; Laing, W. A.; Callaghan, P. T.

1995-09-01

Comparative 31P NMR and 1H NMR imaging experiments at submillimeter pixel resolution were carried out, using a specially constructed solenoidal RF coil. Chemical-shift imaging is used to provide pH maps from the midgut of a Lepidopteran larvae and to demonstrate physiological dependence in the resulting images, The titration curve of pH versus chemical shift for inorganic phosphate is extended beyond the "normal" biological range to the strong alkaline limit.

Dissolved oxygen measurements in aquatic environments: the effects of changing temperature and pressure on three sensor technologies.

PubMed

Markfort, Corey D; Hondzo, Miki

2009-01-01

Dissolved oxygen (DO) is probably the most important parameter related to water quality and biological habitat in aquatic environments. In situ DO sensors are some of the most valuable tools used by scientists and engineers for the evaluation of water quality in aquatic ecosystems. Presently, we cannot accurately measure DO concentrations under variable temperature and pressure conditions. Pressure and temperature influence polarographic and optical type DO sensors compared to the standard Winkler titration method. This study combines laboratory and field experiments to compare and quantify the accuracy and performance of commercially available macro and micro Clark-type oxygen sensors as well as optical sensing technology to the Winkler method under changing pressure and temperature conditions. Field measurements at various lake depths revealed sensor response time up to 11 min due to changes in water temperature, pressure, and DO concentration. Investigators should account for transient response in DO sensors before measurements are collected at a given location. We have developed an effective model to predict the transient response time for Clark-type oxygen sensors. The proposed procedure increases the accuracy of DO data collected in situ for profiling applications.

NMR studies reveal the role of biomembranes in modulating ligand binding and release by intracellular bile acid binding proteins.

PubMed

Pedò, Massimo; Löhr, Frank; D'Onofrio, Mariapina; Assfalg, Michael; Dötsch, Volker; Molinari, Henriette

2009-12-18

Bile acid molecules are transferred vectorially between basolateral and apical membranes of hepatocytes and enterocytes in the context of the enterohepatic circulation, a process regulating whole body lipid homeostasis. This work addresses the role of the cytosolic lipid binding proteins in the intracellular transfer of bile acids between different membrane compartments. We present nuclear magnetic resonance (NMR) data describing the ternary system composed of the bile acid binding protein, bile acids, and membrane mimetic systems, such as anionic liposomes. This work provides evidence that the investigated liver bile acid binding protein undergoes association with the anionic membrane and binding-induced partial unfolding. The addition of the physiological ligand to the protein-liposome mixture is capable of modulating this interaction, shifting the equilibrium towards the free folded holo protein. An ensemble of NMR titration experiments, based on nitrogen-15 protein and ligand observation, confirm that the membrane and the ligand establish competing binding equilibria, modulating the cytoplasmic permeability of bile acids. These results support a mechanism of ligand binding and release controlled by the onset of a bile salt concentration gradient within the polarized cell. The location of a specific protein region interacting with liposomes is highlighted.

Biomimetic supercontainers for size-selective electrochemical sensing of molecular ions

NASA Astrophysics Data System (ADS)

Netzer, Nathan L.; Must, Indrek; Qiao, Yupu; Zhang, Shi-Li; Wang, Zhenqiang; Zhang, Zhen

2017-04-01

New ionophores are essential for advancing the art of selective ion sensing. Metal-organic supercontainers (MOSCs), a new family of biomimetic coordination capsules designed using sulfonylcalix[4]arenes as container precursors, are known for their tunable molecular recognition capabilities towards an array of guests. Herein, we demonstrate the use of MOSCs as a new class of size-selective ionophores dedicated to electrochemical sensing of molecular ions. Specifically, a MOSC molecule with its cavities matching the size of methylene blue (MB+), a versatile organic molecule used for bio-recognition, was incorporated into a polymeric mixed-matrix membrane and used as an ion-selective electrode. This MOSC-incorporated electrode showed a near-Nernstian potentiometric response to MB+ in the nano- to micro-molar range. The exceptional size-selectivity was also evident through contrast studies. To demonstrate the practical utility of our approach, a simulated wastewater experiment was conducted using water from the Fyris River (Sweden). It not only showed a near-Nernstian response to MB+ but also revealed a possible method for potentiometric titration of the redox indicator. Our study thus represents a new paradigm for the rational design of ionophores that can rapidly and precisely monitor molecular ions relevant to environmental, biomedical, and other related areas.

RPA and XPA interaction with DNA structures mimicking intermediates of the late stages in nucleotide excision repair

PubMed Central

Maltseva, Ekaterina A.

2018-01-01

Replication protein A (RPA) and the xeroderma pigmentosum group A (XPA) protein are indispensable for both pathways of nucleotide excision repair (NER). Here we analyze the interaction of RPA and XPA with DNA containing a flap and different size gaps that imitate intermediates of the late NER stages. Using gel mobility shift assays, we found that RPA affinity for DNA decreased when DNA contained both extended gap and similar sized flap in comparison with gapped-DNA structure. Moreover, crosslinking experiments with the flap-gap DNA revealed that RPA interacts mainly with the ssDNA platform within the long gap and contacts flap in DNA with a short gap. XPA exhibits higher affinity for bubble-DNA structures than to flap-gap-containing DNA. Protein titration analysis showed that formation of the RPA-XPA-DNA ternary complex depends on the protein concentration ratio and these proteins can function as independent players or in tandem. Using fluorescently-labelled RPA, direct interaction of this protein with XPA was detected and characterized quantitatively. The data obtained allow us to suggest that XPA can be involved in the post-incision NER stages via its interaction with RPA. PMID:29320546