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

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.

Acid-base characterization of 5-hydroxypyrazine-2-carboxylic acid and the role of ionic equilibria in the optimization of some process conditions for its biocatalytic production.

PubMed

Sak-Bosnar, M; Kovar, K

2005-10-01

This paper describes the use of potentiometric titration to determine the relevant acid-base properties of 5-hydroxypyrazine-2-carboxylic acid (5OH-PYCA), an important intermediate in the production of tuberculostatics. The data obtained were used for calculation of the dissociation constants of 5OH-PYCA. It was found that 5OH-PYCA dissociates in two steps, with the corresponding dissociation constants pK (a1)=3.42 and pK (a2)=7.96, designating 5OH-PYCA as a medium weak acid (1st step). The distribution diagram of dissociated species and the buffer-strength diagram of 5OH-PYCA provide useful information about its behaviour at different pH. The ionic equilibria data obtained can be used for selection of the optimum pH for biotransformation of pyrazine-2-carboxylic acid (PYCA) and for prediction of pH changes during the biotransformation. These data can also be used for selection of the optimum pH for precipitating 5OH-PYCA in downstream processing. All computations have been optimized by mathematical modelling using Solver.

The Reduction of Sulfuryl Chloride at Teflon-Bonded Carbon Cathodes

DTIC Science & Technology

1980-07-01

titrated mulating cathodes, along with their BET surface potentiometrically with standardized silver nitrate areas. Shawinigan black possesses the...assembly steps when individually dissolved can be titrated through were accomplished in the glove box. iodimetry or iodometry, respectively (7). If

Studies on the electron acceptors of photosystem two

NASA Astrophysics Data System (ADS)

Bowden, Simon John

The differences in temperature dependent behaviour and microwave power saturation characteristics between the g=1.9 and g=1.8 QA -Fe2+ signals are described. The dependence of these behaviourial differences on the presence or absence of bicarbonate is emphasised. By studying the EPR signals of QA-Fe2+, Q-Fe2+, Q-Fe2+TBTQ- and the oxidised non-haem iron I have found that detergent solubilisation of BBY PS2 preparations with the detergent OGP, at pH 6.0, results in loss of bicarbonate binding. New preparations, including a dodecylmaltoside prepared CP47, CP4 3, D1, D2, cytochrome bgsg complex, are described which at pH 7.5 retain native bicarbonate binding. These preparations provide a new system for studies into the "bicarbonate effect" because bicarbonate depletion can now be achieved without displacement by another anion. The new OGP particles have been used to investigate both the split pheophytin signal and the two step redox titration phenomenon associated with this signal. The low potential step of the titration was concluded to be independent of the QA/QA- mid-point potential but was found to be linked to the ability to photoreduce pheophytin; once the low potential component, suggested here to be the fluorescence quencher QL, was reduced, pheophytin photoreduction increased. A model is described to explain the two step titration and, from analysis of the signal splitting in +/- HCO3- samples, a possible structural role for bicarbonate is proposed. I have probed the structure of the PS2 electron acceptor region with the protease trypsin. The QA, iron-semiquinone; oxidised non-haem iron and cytochrome bss, EPR signals were all found to be susceptible to trypsin damage, while oxygen evolution with ferricyanide was enhanced by protease treatment. The protective effect of calcium ions against trypsin damage was demonstrated and a possible Ca2+ binding site in the binding region identified.

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.

Titration of individual strains in trivalent live-attenuated influenza vaccine without neutralization.

PubMed

Sirinonthanawech, Naraporn; Surichan, Somchaiya; Namsai, Aphinya; Puthavathana, Pilaipan; Auewarakul, Prasert; Kongchanagul, Alita

2016-11-01

Formulation and quality control of trivalent live-attenuated influenza vaccine requires titration of infectivity of individual strains in the trivalent mix. This is usually performed by selective neutralization of two of the three strains and titration of the un-neutralized strain in cell culture or embryonated eggs. This procedure requires standard sera with high neutralizing titer against each of the three strains. Obtaining standard sera, which can specifically neutralize only the corresponding strain of influenza viruses and is able to completely neutralize high concentration of virus in the vaccine samples, can be a problem for many vaccine manufacturers as vaccine stocks usually have very high viral titers and complete neutralization may not be obtained. Here an alternative approach for titration of individual strain in trivalent vaccine without the selective neutralization is presented. This was done by detecting individual strains with specific antibodies in an end-point titration of a trivalent vaccine in cell culture. Similar titers were observed in monovalent and trivalent vaccines for influenza A H3N2 and influenza B strains, whereas the influenza A H1N1 strain did not grow well in cell culture. Viral interference among the vaccine strains was not observed. Therefore, providing that vaccine strains grow well in cell culture, this assay can reliably determine the potency of individual strains in trivalent live-attenuated influenza vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of a specific HPLC determination of toxic aconite alkaloids in processed Radix aconiti with a titration method of total alkaloids.

PubMed

Csupor, Dezso; Borcsa, Botond; Heydel, Barbara; Hohmann, Judit; Zupkó, István; Ma, Yan; Widowitz, Ute; Bauer, Rudolf

2011-10-01

In traditional Chinese medicine, Aconitum (Ranunculaceae) roots are only applied after processing. Nevertheless, several cases of poisoning by improperly processed aconite roots have been reported. The aim of this study was to develop a reliable analytical method to assess the amount of toxic aconite alkaloids in commercial aconite roots, and to compare this method with the commonly used total alkaloid content determination by titration. The content of mesaconitine, aconitine, and hypaconitine in 16 commercial samples of processed aconite roots was determined by an HPLC method and the total alkaloid content by indirect titration. Five samples were selected for in vivo toxicological investigation. In most of the commercial samples, toxic alkaloids were not detectable, or only traces were found. In four samples, we could detect >0.04% toxic aconite alkaloids, the highest with a content of 0.16%. The results of HPLC analysis were compared with the results obtained by titration, and no correlation was found between the two methods. The in vivo results reassured the validity of the HPLC determination. Samples with mesaconitine, aconitine, and hypaconitine content below the HPLC detection limit still contained up to 0.2% alkaloids determined by titration. Since titration of alkaloids gives no information selectively on the aconitine-type alkaloid content and toxicity of aconite roots this method is not appropriate for safety assessment. The HPLC method developed by us provides a quick and reliable assessment of toxicity and should be considered as a purity test in pharmacopoeia monographs.

Field ion microscopic studies of the CO oxidation on platinum: Field ion imaging and titration reactions

NASA Astrophysics Data System (ADS)

Gorodetskii, V.; Drachsel, W.; Block, J. H.

1994-05-01

Elementary steps of the CO oxidation—which are important for understanding the oscillatory behavior of this catalytic reaction—are investigated simultaneously on different Pt-single crystal surfaces by field ion microscopy. Due to preferential ionization probabilities of oxygen as imaging gas on those surface sites, which are adsorbed with oxygen, these sites can be imaged in a lateral resolution on the atomic scale. In the titration reaction a COad-precovered field emitter surface reacts with gaseous oxygen adsorbed from the gas phase or, vice versa, the Oad-precovered surface with carbon monoxide adsorbed from the gas phase. The competition of the manifold of single crystal planes exposed to the titration reaction at the field emitter tip is studied. The surface specificity can be documented in the specific reaction delay times of the different planes and in the propagation rates of the reaction-diffusion wave fronts measured on these individual planes during the titration reaction with a time resolution of 40 ms. At 300 K the COad-precovered surfaces display the {011} regions, precisely the {331} planes as the most active, followed by {012}, {122}, {001}, and finally by {111}. Reaction wave fronts move with a velocity of 8 Å/s at {012}, with ≊0.8 Å/s at {111}, and have a very fast ``switch-on'' reaction at the (001) plane with 500 Å/s. At higher temperature, T=350 K, an acceleration of reaction rates is combined with shorter delay times. The titration reaction of a precovered Oad surface with COgas at T=373 K shows the formation of CO islands starting in the {011} regions with a quickly moving reaction front into the other surface areas without showing particular delay times for different surface symmetries. The two reverse titration reactions have a largely different character. The titration of COad with oxygen adsorbed from the gas phase consists of three different steps, (i) the induction times, (ii) the highly surface specific reaction, and (iii) different rates of wave front propagation. The reaction of COgas with a precovered Oad layer on the other hand starts with nucleating islands around the {011} planes from where the whole emitter surface is populated with COad without pronounced surface specifity.

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.

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.

The two-step assemblies of basic-amino-Acid-rich Peptide with a highly charged polyoxometalate.

PubMed

Zhang, Teng; Li, Hong-Wei; Wu, Yuqing; Wang, Yizhan; Wu, Lixin

2015-06-15

Two-step assembly of a peptide from HPV16 L1 with a highly charged europium-substituted polyoxometalate (POM) cluster, accompanying a great luminescence enhancement of the inorganic polyanions, is reported. The mechanism is discussed in detail by analyzing the thermodynamic parameters from isothermal titration calorimetry (ITC), time-resolved fluorescent and NMR spectra. By comparing the actions of the peptide analogues, a binding process and model are proposed accordingly. The driving forces in each binding step are clarified, and the initial POM aggregation, basic-sequence and hydrophobic C termini of peptide are revealed to contribute essentially to the two-step assembly. The present study demonstrates both a meaningful preparation for bioinorganic materials and a strategy using POMs to modulate the assembly of peptides and even proteins, which could be extended to other proteins and/or viruses by using peptides and POMs with similar properties. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Sorption of Cu and Pb to kaolinite-fulvic acid colloids: Assessment of sorbent interactions

NASA Astrophysics Data System (ADS)

Heidmann, Ilona; Christl, Iso; Kretzschmar, Ruben

2005-04-01

The sorption of Cu(II) and Pb(II) to kaolinite-fulvic acid colloids was investigated by potentiometric titrations. To assess the possible interactions between kaolinite and fulvic acid during metal sorption, experimental sorption isotherms were compared with predictions based on a linear additivity model (LAM). Suspensions of 5 g L -1 kaolinite and 0.03 g L -1 fulvic acid in 0.01 M NaNO 3 were titrated with Cu and Pb solutions, respectively. The suspension pH was kept constant at pH 4, 6, or 8. The free ion activities of Cu 2+ and Pb 2+ were monitored in the titration vessel using ion selective electrodes. Total dissolved concentrations of metals (by ICP-MS) and fulvic acid (by UV-absorption) were determined in samples taken after each titration step. The amounts of metals sorbed to the solid phase, comprised of kaolinite plus surface-bound fulvic acid, were calculated by difference. Compared to pure kaolinite, addition of fulvic acid to the clay strongly increased metal sorption to the solid phase. This effect was more pronounced at pH 4 and 6 than at pH 8, because more fulvic acid was sorbed to the kaolinite surface under acidic conditions. Addition of Pb enhanced the sorption of fulvic acid onto kaolinite at pH 6 and 8, but not at pH 4. Addition of Cu had no effect on the sorption of fulvic acid onto kaolinite. In the LAM, metal sorption to the kaolinite surface was predicted by a two-site, 1-pK basic Stern model and metal sorption to the fulvic acid was calculated with the NICA-Donnan model, respectively. The LAM provided good predictions of Cu sorption to the kaolinite-fulvic acid colloids over the entire range in pH and free Cu 2+ ion activity (10 -12 to 10 -5). The sorption of Pb was slightly underestimated by the LAM under most conditions. A fractionation of the fulvic acid during sorption to kaolinite was observed, but this could not explain the observed deviations of the LAM predictions from the experimental Pb sorption isotherms.

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

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.

Ozone-induced changes in natural organic matter (NOM) structure

USGS Publications Warehouse

Westerhoff, P.; Debroux, J.; Aiken, G.; Amy, G.

1999-01-01

Hydrophobic organic acids (combined humic and fulvic acids), obtained from an Antarctic Lake with predominantly microbially derived organic carbon sources and two US fiver systems with terrestrial organic carbon sources, were ozonated. Several analyses, including 13C-NMR, UV absorbance, fluorescence, hydrophobic/transphilic classification, and potentiometric titrations, were performed before and after ozonation. Ozonation reduced aromatic carbon content, selectively reducing phenolic carbon content. Ozonation of the samples resulted in increased aliphatic, carboxyl, plus acetal and ketal anomeric carbon content and shifted towards less hydrophobic compounds.Hydrophobic organic acids (combined humic and fulvic acids), obtained from an Antarctic Lake with predominantly microbially derived organic carbon sources and two US river systems with terrestrial organic carbon sources, were ozonated. Several analyses, including 13C-NMR, UV absorbance, fluorescence, hydrophobic/transphilic classification, and potentiometric titrations, were performed before and after ozonation. Ozonation reduced aromatic carbon content, selectively reducing phenolic carbon content. Ozonation of the samples resulted in increased aliphatic, carboxyl, plus acetal and ketal anomeric carbon content and shifted towards less hydrophobic compounds.

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.

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.

The safety, tolerability, pharmacokinetics and cognitive effects of GSK239512, a selective histamine H₃ receptor antagonist in patients with mild to moderate Alzheimer's disease: a preliminary investigation.

PubMed

Nathan, Pradeep J; Boardley, Rebecca; Scott, Nicola; Berges, Alienor; Maruff, Paul; Sivananthan, Tharani; Upton, Neil; Lowy, Martin T; Nestor, Peter J; Lai, Robert

2013-03-01

The histamine H3 receptor plays a critical role in the negative neuromodulation of neurotransmitters involved in cognitive function. H3 receptor antagonists/inverse agonists have been shown to exert pro-cognitive effects in pre-clinical models. GSK239512 is a potent and selective H₃ receptor antagonist developed for the treatment of cognitive dysfunction in neurodegenerative disorders. In this study we examined the safety, tolerability, pharmacokinetics and pro-cognitive effects of GSK239512 (oral) in patients with mild to moderate Alzheimer's disease using ascending dose titration regimens. The study was conducted in two parts. Part A was a single-blind, placebo run-in, flexible dose titration over 9 days in two cohorts, each consisting of two patients. Part B was a double-blind, randomised, placebo controlled, parallel group, which investigated 3 flexible dose titration regimens over 4 weeks in 3 cohorts, each consisting of eight patients. Overall, the 5/10/20/40 μg and 10/20/40/80 μg regimens were well-tolerated. The regimen of 20/40/80/150 μg showed the poorest tolerability likely due to the higher starting dose. There were no clinically significant abnormalities in haematology, clinical chemistry, urinalysis parameters and cardiovascular parameters. GSK239512 had positive effects on tasks of attention and memory with effect sizes between 0.56 and 1.37. GSK239512 displayed asatisfactory level of tolerability in patients with Alzheimer's disease with evidence for positive effects on attention and memory. The findings suggest that a titration regimen with a starting dose of 5-10 μg and a maximum dose of 80 μg is likely to be a well-tolerated and potentially efficacious regimen for future clinical trials in patients with Alzheimer's disease. These findings await replication in a larger study.

Analysis of Aircraft Fuels and Related Materials

DTIC Science & Technology

1982-09-01

content by the Karl Fischer method . Each 2040 solvent sample represented a different step in a clean-up procedure conducted by Aero Propulsion...izes a potentiometric titration with alcoholic silver nitrate. This method has a minimum detectability of 1 ppm. It has a re- peatability of 0.1 ppm... Method 163-80, which util- izes a potentiometric titration with alcoholic silver nitrate. This method has a minimum detectability of 1 ppm and has a

[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.

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.

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

[Dose-finding for treatment with a transdermal fentanyl patch : Titration with oral transmucosal fentanyl citrate and morphine sulfate].

PubMed

Mücke, M; Conrad, R; Marinova, M; Cuhls, H; Elsner, F; Rolke, R; Radbruch, L

2016-12-01

To date, no studies investigating titration with oral transmucosal fentanyl for the dose-finding of transdermal fentanyl treatment have been published. In an open randomized study 60 patients with chronic malignant (n = 39) or nonmalignant pain (n = 21), who required opioid therapy according to step three of the guidelines of the World Health Organization (WHO), were investigated. In two groups of 30 patients each titration with immediate release morphine (IRM) or oral transmucosal fentanyl citrate (OTFC) was undertaken. For measurement purposes the Brief Pain Inventory (BPI) and Minimal Documentation System (MIDOS) were used. After a 24-h titration phase, in which patients documented the intensity of pain, nausea, and tiredness, treatment with transdermal fentanyl was evaluated over a 10-day period by means of the necessary dose adaptation (responder ≤ 1 dose adaptation; conversion formula 1:1 [OTFC group] vs 100:1 [IRM group]).The pain reduction over the first 24 h (titration phase) did not differ significantly between the groups. The number of responders (17 OTFC vs. 21 IRM) over the 10-day period did not show any difference either. In both groups there was a significant reduction in pain intensity (p < 0.001). Over the course of the study, there were significantly more drop-outs because of adverse effects in the OTFC group than in the IRM group (8 vs 1, p = 0.028).Oral transmucosal fentanyl citrate can be applied for the titration of transdermal fentanyl, but it does not show any clinically relevant advantage. For example, the risk of side effects-induced drop-outs was greater in the present study. Whether the unnecessary opioid switching to treat chronic pain and breakthrough pain is advantageous with regard to minimizing conversion errors cannot be definitively answered within the scope of this study.

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

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.

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

Comparative Analysis of Anterior Chamber Flare Grading between Clinicians with Different Levels of Experience and Semi-automated Laser Flare Photometry.

PubMed

Agrawal, Rupesh; Keane, Pearse A; Singh, Jasmin; Saihan, Zubin; Kontos, Andreas; Pavesio, Carlos E

2016-01-01

To assess correlation for anterior chamber flare grading between clinicians with different levels of experience and with semi-automated flare reading in a cohort of patients with heterogeneous uveitic entities. Fifty-nine observations from 36 patients were recorded and analyzed for statistical association. In each patient, flare was assessed objectively using the Kowa FM-700 laser flare photometer, and subjective masked grading by two clinicians was performed. The study demonstrated disparity in flare readings between clinical graders with one step disagreement in clinical grading in 26 (44.06%) eyes (p < 0.001) and concordance between the flare readings by experienced grader and flare photometry. After review of semi-automated flare readings, management was changed in 11% of the patients. Laser flare photometry can be a valuable tool to remove the observer bias in grading flare for selected cohort of uveitis patients. It can be further applied to titrate therapy in intraocular inflammation.

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…

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.

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

COPPER COMPLEXATION BY NATURAL ORGANIC MATTER IN CONTAMINATED AND UNCOMTAINATED GROUND WATER

EPA Science Inventory

Ground-water samples were collected from an uncontaminated and a contaminated site. Copper complexation was characterized by ion-selective electrode (ISE), fluorescence quenching (FQ), and cathodic stripping voltammetric (CSV) titrations. All of the samples were titrated at their...

A one-step colorimetric acid-base titration sensor using a complementary color changing coordination system.

PubMed

Cho, Hui Hun; Kim, Si Hyun; Heo, Jun Hyuk; Moon, Young Eel; Choi, Young Hun; Lim, Dong Cheol; Han, Kwon-Hoon; Lee, Jung Heon

2016-06-21

We report the development of a colorimetric sensor that allows for the quantitative measurement of the acid content via acid-base titration in a single-step. In order to create the sensor, we used a cobalt coordination system (Co-complex sensor) that changes from greenish blue colored Co(H2O)4(OH)2 to pink colored Co(H2O)6(2+) after neutralization. Greenish blue and pink are two complementary colors with a strong contrast. As a certain amount of acid is introduced to the Co-complex sensor, a portion of greenish blue colored Co(H2O)4(OH)2 changes to pink colored Co(H2O)6(2+), producing a different color. As the ratio of greenish blue and pink in the Co-complex sensor is determined by the amount of neutralization reaction occurring between Co(H2O)4(OH)2 and an acid, the sensor produced a spectrum of green, yellow green, brown, orange, and pink colors depending on the acid content. In contrast, the color change appeared only beyond the end point for normal acid-base titration. When we mixed this Co-complex sensor with different concentrations of citric acid, tartaric acid, and malic acid, three representative organic acids in fruits, we observed distinct color changes for each sample. This color change could also be observed in real fruit juice. When we treated the Co-complex sensor with real tangerine juice, it generated diverse colors depending on the concentration of citric acid in each sample. These results provide a new angle on simple but quantitative measurements of analytes for on-site usage in various applications, such as in food, farms, and the drug industry.

Colloidal titration of aqueous zirconium solutions with poly(vinyl sulfate) by potentiometric endpoint detection using a toluidine blue selective electrode.

PubMed

Sakurada, Osamu; Kato, Yasutake; Kito, Noriyoshi; Kameyama, Keiichi; Hattori, Toshiaki; Hashiba, Minoru

2004-02-01

Zirconium oxy-salts were hydrolyzed to form positively charged polymer or cluster species in acidic solutions. The zirconium hydrolyzed polymer was found to react with a negatively charged polyelectrolyte, such as poly(vinyl sulfate), and to form a stoichiometric polyion complex. Thus, colloidal titration with poly(vinyl sulfate) was applied to measure the zirconium concentration in an acidic solution by using a Toluidine Blue selective plasticized poly(vinyl chloride) membrane electrode as a potentiometric end-point detecting device. The determination could be performed with 1% of the relative standard deviation. The colloidal titration stoichiometry at pH < or = 2 was one mol of zirconium per equivalent mol of poly(vinyl sulfate).

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.

Sodium and potassium competition in potassium-selective and non-selective channels

NASA Astrophysics Data System (ADS)

Sauer, David B.; Zeng, Weizhong; Canty, John; Lam, Yeeling; Jiang, Youxing

2013-11-01

Potassium channels selectively conduct K+, primarily to the exclusion of Na+, despite the fact that both ions can bind within the selectivity filter. Here we perform crystallographic titration and single-channel electrophysiology to examine the competition of Na+ and K+ binding within the filter of two NaK channel mutants; one is the potassium-selective NaK2K mutant and the other is the non-selective NaK2CNG, a CNG channel pore mimic. With high-resolution structures of these engineered NaK channel constructs, we explicitly describe the changes in K+ occupancy within the filter upon Na+ competition by anomalous diffraction. Our results demonstrate that the non-selective NaK2CNG still retains a K+-selective site at equilibrium, whereas the NaK2K channel filter maintains two high-affinity K+ sites. A double-barrier mechanism is proposed to explain K+ channel selectivity at low K+ concentrations.

"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.

Near-infrared noninvasive spectroscopic determination of pH

DOEpatents

Alam, Mary K.; Robinson, Mark R.

1998-08-11

Methods and apparatus for, preferably, determining noninvasively and in vitro pH in a human. The non-invasive method includes the steps of: generating light at three or more different wavelengths in the range of 1000 nm to 2500 nm; irradiating blood containing tissue; measuring the intensities of the wavelengths emerging from the blood containing tissue to obtain a set of at least three spectral intensities v. wavelengths; and determining the unknown values of pH. The determination of pH is made by using measured intensities at wavelengths that exhibit change in absorbance due to histidine titration. Histidine absorbance changes are due to titration by hydrogen ions. The determination of the unknown pH values is performed by at least one multivariate algorithm using two or more variables and at least one calibration model. The determined pH values are within the physiological ranges observed in blood containing tissue. The apparatus includes a tissue positioning device, a source, at least one detector, electronics, a microprocessor, memory, and apparatus for indicating the determined values.

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

Temperature modulation and quadrature detection for selective titration of two-state exchanging reactants.

PubMed

Zrelli, K; Barilero, T; Cavatore, E; Berthoumieux, H; Le Saux, T; Croquette, V; Lemarchand, A; Gosse, C; Jullien, L

2011-04-01

Biological samples exhibit huge molecular diversity over large concentration ranges. Titrating a given compound in such mixtures is often difficult, and innovative strategies emphasizing selectivity are thus demanded. To overcome limitations inherent to thermodynamics, we here present a generic technique where discrimination relies on the dynamics of interaction between the target of interest and a probe introduced in excess. Considering an ensemble of two-state exchanging reactants submitted to temperature modulation, we first demonstrate that the amplitude of the out-of-phase concentration oscillations is maximum for every compound involved in a reaction whose equilibrium constant is equal to unity and whose relaxation time is equal to the inverse of the excitation angular frequency. Taking advantage of this feature, we next devise a highly specific detection protocol and validate it using a microfabricated resistive heater and an epifluorescence microscope, as well as labeled oligonucleotides to model species displaying various dynamic properties. As expected, quantification of a sought for strand is obtained even if interfering reagents are present in similar amounts. Moreover, our approach does not require any separation and is compatible with imaging. It could then benefit some of the numerous binding assays performed every day in life sciences.

Synthesis, physico-chemical properties and complexing abilities of new amphiphilic ligands from D-galacturonic acid.

PubMed

Allam, Anas; Behr, Jean-Bernard; Dupont, Laurent; Nardello-Rataj, Véronique; Plantier-Royon, Richard

2010-04-19

This paper describes a convenient and efficient synthesis of new complexing surfactants from d-galacturonic acid and n-octanol as renewable raw materials in a two-step sequence. In the first step, simultaneous O-glycosidation-esterification under Fischer conditions was achieved. The anomeric ratio of the products was studied based on the main experimental parameters and the activation mode (thermal or microwave). In the second step, aminolysis of the n-octyl ester was achieved with various functionalized primary amines under standard thermal or microwave activation. The physico-chemical properties of these new amphiphilic ligands were measured and these compounds were found to exhibit interesting surface properties. Complexing abilities of one uronamide ligand functionalized with a pyridine moiety toward Cu(II) ions was investigated in solution by EPR titrations. A solid compound was also synthesized and characterized, its relative structure was deduced from spectroscopic data. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Surface grafting of cellulose nanocrystals with poly(ethylene oxide) in aqueous media.

PubMed

Kloser, Elisabeth; Gray, Derek G

2010-08-17

Aqueous suspensions of poly(ethylene oxide)-grafted nanocrystalline cellulose (PEO-grafted NCC) were prepared in order to achieve steric instead of electrostatic stabilization. A two-step process was employed: in the first step NCC suspensions prepared by sulfuric acid hydrolysis were desulfated with sodium hydroxide, and in the second step the surfaces of the crystals were functionalized with epoxy-terminated poly(ethylene oxide) (PEO epoxide) under alkaline conditions. The PEO-grafted samples were analyzed by conductometric titration, ATR-IR, solid-state NMR, MALDI-TOF MS, SEC MALLS, and AFM. The covalent nature of the linkage was confirmed by weight increase and MALDI-TOF analysis. The PEO-grafted cellulose nanocrystals (CNCs) formed a stable colloidal suspension that remained well dispersed, while the desulfated nanoparticles aggregated and precipitated. Upon concentration of the PEO-grafted aqueous NCC suspension, a chiral nematic phase was observed.

Conformational stability and thermodynamic characterization of the lipoic acid bearing domain of human mitochondrial branched chain α-ketoacid dehydrogenase

PubMed Central

Naik, Mandar T.; Huang, Tai-Huang

2004-01-01

The lipoic acid bearing domain (hbLBD) of human mitochondrial branched chain α-ketoacid dehydrogenase (BCKD) plays important role of substrate channeling in oxidative decarboxylation of the branched chain α-ketoacids. Recently hbLBD has been found to follow two-step folding mechanism without detectable presence of stable or kinetic intermediates. The present study describes the conformational stability underlying the folding of this small β-barrel domain. Thermal denaturation in presence of urea and isothermal urea denaturation titrations are used to evaluate various thermodynamic parameters defining the equilibrium unfolding. The linear extrapolation model successfully describes the two-step; native state ↔denatured state unfolding transition of hbLBD. The average temperature of maximum stability of hbLBD is estimated as 295.6 ± 0.9 K. Cold denaturation of hbLBD is also predicted and discussed. PMID:15322287

Virtual Allergist

MedlinePlus

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Theoretical investigation of isotope exchange reaction in tritium-contaminated mineral oil in vacuum pump.

PubMed

Dong, Liang; Xie, Yun; Du, Liang; Li, Weiyi; Tan, Zhaoyi

2015-04-28

The mechanism of the isotope exchange reaction between molecular tritium and several typical organic molecules in vacuum pump mineral oil has been investigated by density functional theory (DFT), and the reaction rates are determined by conventional transition state theory (TST). The tritium-hydrogen isotope exchange reaction can proceed with two different mechanisms, the direct T-H exchange mechanism and the hyrogenation-dehydrogenation exchange mechanism. In the direct exchange mechanism, the titrated product is obtained through one-step via a four-membered ring hydrogen migration transition state. In the hyrogenation-dehydrogenation exchange mechanism, the T-H exchange could be accomplished by the hydrogenation of the unsaturated bond with tritium followed by the dehydrogenation of HT. Isotope exchange between hydrogen and tritium is selective, and oil containing molecules with OH and COOH groups can more easily exchange hydrogen for tritium. For aldehydes and ketones, the ability of T-H isotope exchange can be determined by the hydrogenation of T2 or the dehydrogenation of HT. The molecules containing one type of hydrogen provide a single product, while the molecules containing different types of hydrogens provide competitive products. The rate constants are presented to quantitatively estimate the selectivity of the products. Copyright © 2015 Elsevier B.V. All rights reserved.

Fermentation of enset (Ensete ventricosum) in the Gamo highlands of Ethiopia: Physicochemical and microbial community dynamics.

PubMed

Andeta, A F; Vandeweyer, D; Woldesenbet, F; Eshetu, F; Hailemicael, A; Woldeyes, F; Crauwels, S; Lievens, B; Ceusters, J; Vancampenhout, K; Van Campenhout, L

2018-08-01

Enset (Ensete ventricosum) provides staple food for 15 million people in Ethiopia after fermentation into kocho. The fermentation process has hardly been investigated and is prone to optimization. The aim of this study was to investigate the physicochemical and microbial dynamics of fermentation practices in the Gamo highlands. These practices show local variation, but two steps were omnipresent: scraping of the pseudostem and fermenting it in a pit or a bamboo basket. Enset plants were fragmented and fermented for two months in order to investigate the physicochemical (temperature, moisture content, pH and titratable acidity) and microbial dynamics (total viable aerobic counts, counts of Enterobacteriaceae, lactic acid bacteria, yeasts and moulds and Clostridium spores counts, and Illumina Miseq sequencing). Samples were taken on days 1, 7, 15, 17, 31 and 60. The pH decreased, whereas the titratable acidity increased during fermentation. Of all counts those of lactic acid bacteria and Clostridium spores increased during fermentation. Leuconostoc mesenteroides initiated the fermentation. Later on, Prevotella paludivivens, Lactobacillus sp. and Bifidobacterium minimum dominated. These three species are potential candidates for the development of a starter culture. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

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

[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%.

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.

The binding of manganese(II) and zinc(II) to the synthetic oligonucleotide d(C-G-C-G-A-A-T-T-C-G-C-G)2. A 1H NMR study.

PubMed

Frøystein, N A; Sletten, E

1991-03-01

The interaction of the synthetic oligonucleotide d(C-G-C-G-A-A-T-T-C-G-C-G)2 with two different transition-metal ions has been investigated in aqueous solution by means of 1H NMR spectroscopy. The effects on the DNA due to the presence of manganese(II) or zinc(II) have been monitored by observing the paramagnetic broadening and diamagnetic shifts of the non-exchangeable proton resonance lines, respectively. The 1H NMR spectra acquired during the course of the manganese(II) titration show very distinct broadening effects on certain DNA resonance lines. Primarily, the H8 resonance of G4 is affected, but also the H5 and H6 resonances of C3 are clearly affected by the metal. The results imply that the binding of manganese(II) to DNA is sequence specific. The 1H spectra obtained during the zinc(II) titration reveal diamagnetic shift effects which largely conform with the paramagnetic broadening effects due to the presence of manganese(II), although this picture is somewhat more complex. The H8 resonance of G4 displays a clearly visible high-field shift, while for the other guanosine H8 protons this effect is absent. The H1' and H2' protons of C3 show an effect of similar strength, although in the opposite direction, while H5 and H6 of C3 are only slightly affected. Local differences in the structure of the DNA and the basicities of potential binding sites on different base steps in the sequence might account for the observed sequence selectivity.

Students' integration of multiple representations in a titration experiment

NASA Astrophysics Data System (ADS)

Kunze, Nicole M.

A complete understanding of a chemical concept is dependent upon a student's ability to understand the microscopic or particulate nature of the phenomenon and integrate the microscopic, symbolic, and macroscopic representations of the phenomenon. Acid-base chemistry is a general chemistry topic requiring students to understand the topics of chemical reactions, solutions, and equilibrium presented earlier in the course. In this study, twenty-five student volunteers from a second semester general chemistry course completed two interviews. The first interview was completed prior to any classroom instruction on acids and bases. The second interview took place after classroom instruction, a prelab activity consisting of a titration calculation worksheet, a titration computer simulation, or a microscopic level animation of a titration, and two microcomputer-based laboratory (MBL) titration experiments. During the interviews, participants were asked to define and describe acid-base concepts and in the second interview they also drew the microscopic representations of four stages in an acid-base titration. An analysis of the data showed that participants had integrated the three representations of an acid-base titration to varying degrees. While some participants showed complete understanding of acids, bases, titrations, and solution chemistry, other participants showed several alternative conceptions concerning strong acid and base dissociation, the formation of titration products, and the dissociation of soluble salts. Before instruction, participants' definitions of acid, base, and pH were brief and consisted of descriptive terms. After instruction, the definitions were more scientific and reflected the definitions presented during classroom instruction.

Study of neurontin: titrate to effect, profile of safety (STEPS) trial: a narrative account of a gabapentin seeding trial.

PubMed

Krumholz, Samuel D; Egilman, David S; Ross, Joseph S

2011-06-27

Seeding trials, clinical studies conducted by pharmaceutical companies for marketing purposes, have rarely been described in detail. We examined all documents relating to the clinical trial Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) produced during the Neurontin marketing, sales practices, and product liability litigation, including company internal and external correspondence, reports, and presentations, as well as depositions elicited in legal proceedings of Harden Manufacturing vs Pfizer and Franklin vs Warner-Lambert, most which were created between 1990 and 2009. Using a systematic search strategy, we identified and reviewed all documents related to the STEPS trial in order to identify key themes related to the trial's conduct and determine the extent of marketing involvement in its planning and implementation. Documents demonstrated that STEPS was a seeding trial posing as a legitimate scientific study. Documents consistently described the trial itself, not trial results, to be a marketing tactic in the company's marketing plans. Documents demonstrated that at least 2 external sources questioned the validity of the study before execution, and that data quality during the study was often compromised. Furthermore, documents described company analyses examining the impact of participating as a STEPS investigator on rates and dosages of gabapentin prescribing, finding a positive association. None of these findings were reported in 2 published articles. The STEPS trial was a seeding trial, used to promote gabapentin and increase prescribing among investigators, and marketing was extensively involved in its planning and implementation.

On the binding of calcium by micelles composed of carboxy-modified pluronics measured by means of differential potentiometric titration and modeled with a self-consistent-field theory.

PubMed

Lauw, Y; Leermakers, F A M; Cohen Stuart, M A; Pinheiro, J P; Custers, J P A; van den Broeke, L J P; Keurentjes, J T F

2006-12-19

We perform differential potentiometric titration measurements for the binding of Ca2+ ions to micelles composed of the carboxylic acid end-standing Pluronic P85 block copolymer (i.e., CAE-85 (COOH-(EO)26-(PO)39-(EO)26-COOH)). Two different ion-selective electrodes (ISEs) are used to detect the free calcium concentration; the first ISE is an indicator electrode, and the second is a reference electrode. The titration is done by adding the block copolymers to a known solution of Ca2+ at neutral pH and high enough temperature (above the critical micellization temperature CMT) and various amount of added monovalent salt. By measuring the difference in the electromotive force between the two ISEs, the amount of Ca2+ that is bound by the micelles is calculated. This is then used to determine the binding constant of Ca2+ with the micelles, which is a missing parameter needed to perform molecular realistic self-consistent-field (SCF) calculations. It turns out that the micelles from block copolymer CAE-85 bind Ca2+ ions both electrostatically and specifically. The specific binding between Ca2+ and carboxylic groups in the corona of the micelles is modeled through the reaction equilibrium -COOCa+ <==> -COO- + Ca2+ with pKCa = 1.7 +/- 0.06.

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.

Determination of total fluoride in HF/HNO3/H2SiF6 etch solutions by new potentiometric titration methods.

PubMed

Weinreich, Wenke; Acker, Jörg; Gräber, Iris

2007-03-30

In the photovoltaic industry the etching of silicon in HF/HNO(3) solutions is a decisive process for cleaning wafer surfaces or to produce certain surface morphologies like polishing or texturization. With regard to cost efficiency, a maximal utilisation of etch baths in combination with highest quality and accuracy is strived. To provide an etch bath control realised by a replenishment with concentrated acids the main constituents of these HF/HNO(3) etch solutions including the reaction product H(2)SiF(6) have to be analysed. Two new methods for the determination of the total fluoride content in an acidic etch solution based on the precipitation titration with La(NO(3))(3) are presented within this paper. The first method bases on the proper choice of the reaction conditions, since free fluoride ions have to be liberated from HF and H(2)SiF(6) at the same time to be detected by a fluoride ion-selective electrode (F-ISE). Therefore, the sample is adjusted to a pH of 8 for total cleavage of the SiF(6)(2-) anion and titrated in absence of buffers. In a second method, the titration with La(NO(3))(3) is followed by a change of the pH-value using a HF resistant glass-electrode. Both methods provide consistent values, whereas the analysis is fast and accurate, and thus, applicable for industrial process control.

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.

Assessing the acid-base and conformational properties of histidine residues in human prion protein (125-228) by means of pK(a) calculations and molecular dynamics simulations.

PubMed

Langella, Emma; Improta, Roberto; Crescenzi, Orlando; Barone, Vincenzo

2006-07-01

A thorough study of the acid-base behavior of the four histidines and the other titratable residues of the structured domain of human prion protein (125-228) is presented. By using multi-tautomer electrostatic calculations, average titration curves have been built for all titratable residues, using the whole bundles of NMR structures determined at pH 4.5 and 7.0. According to our results, (1) only histidine residues are likely to be involved in the first steps of the pH-driven conformational transition of prion protein; (2) the pK(a)'s of His140 and His177 are approximately 7.0, whereas those of His155 and His187 are < 5.5. 10-ns long molecular dynamics simulations have been performed on five different models, corresponding to the most significant combinations of histidine protonation states. A critical comparison between the available NMR structures and our computational results (1) confirms that His155 and His187 are the residues whose protonation is involved in the conformational rearrangement of huPrP in mildly acidic condition, and (2) shows how their protonation leads to the destructuration of the C-terminal part of HB and to the loss of the last turn of HA that represent the crucial microscopic steps of the rearrangement. (c) 2006 Wiley-Liss, Inc.

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.

The Quantitative Resolution of a Mixture of Group II Metal Ions by Thermometric Titration with EDTA. An Analytical Chemistry Experiment.

ERIC Educational Resources Information Center

Smith, Robert L.; Popham, Ronald E.

1983-01-01

Presents an experiment in thermometric titration used in an analytic chemistry-chemical instrumentation course, consisting of two titrations, one a mixture of calcium and magnesium, the other of calcium, magnesium, and barium ions. Provides equipment and solutions list/specifications, graphs, and discussion of results. (JM)

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.

A simple and rapid Hepatitis A Virus (HAV) titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

PubMed Central

Konduru, Krishnamurthy; Virata-Theimer, Maria Luisa; Yu, Mei-ying W; Kaplan, Gerardo G

2008-01-01

Background Hepatitis A virus (HAV), the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA) based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd) resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG) preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the endpoint dilution ELISA. The ARTA reduced the labour, time, and cost of HAV titrations making it suitable for high throughput screening of sera and antivirals, determination of anti-HAV antibodies in human immune globulin preparations, and research applications that involve the routine evaluation of HAV titers. PMID:19094229

Adsorption of xenon on vicinal copper and platinum surfaces

NASA Astrophysics Data System (ADS)

Baker, Layton

The adsorption of xenon was studied on Cu(111), Cu(221), Cu(643) and on Pt(111), Pt(221), and Pt(531) using low energy electron diffraction (LEED), temperature programmed desorption (TPD) of xenon, and ultraviolet photoemission of adsorbed xenon (PAX). These experiments were performed to study the atomic and electronic structure of stepped and step-kinked, chiral metal surfaces. Xenon TPD and PAX were performed on each surface in an attempt to titrate terrace, step edge, and kink adsorption sites by adsorption energetics (TPD) and local work function differences (PAX). Due to the complex behavior of xenon on the vicinal copper and platinum metal surfaces, adsorption sites on these surfaces could not be adequately titrated by xenon TPD. On Cu(221) and Cu(643), xenon desorption from step adsorption sites was not apparent leading to the conclusion that the energy difference between terrace and step adsorption is minuscule. On Pt(221) and Pt(531), xenon TPD indicated that xenon prefers to bond at step edges and that the xenon-xenon interaction at step edges in repulsive but no further indication of step-kink adsorption was observed. The Pt(221) and Pt(531) TPD spectra indicated that the xenon overlayer undergoes strong compression near monolayer coverage on these surfaces due to repulsion between step-edge adsorbed xenon and other encroaching xenon atoms. The PAX experiments on the copper and platinum surfaces demonstrated that the step adsorption sites have lower local work functions than terrace adsorption sites and that higher step density leads to a larger separation in the local work function of terrace and step adsorption sites. The PAX spectra also indicated that, for all surfaces studied at 50--70 K, step adsorption is favored at low coverage but the step sites are not saturated until monolayer coverage is reached; this observation is due to the large entropy difference between terrace and step adsorption states and to repulsive interactions between xenon atoms adsorbed at step edges (on the platinum surfaces). The results herein provide several novel observations regarding the adsorptive behavior of xenon on vicinal copper and platinum surfaces.

Assessment of Knowledge of Self Blood Glucose Monitoring and Extent of Self Titration of Anti-Diabetic Drugs among Diabetes Mellitus Patients - A Cross Sectional, Community Based Study.

PubMed

Krishnan, V; Thirunavukkarasu, J

2016-03-01

Self blood glucose monitoring is an important context of self care in the management of diabetes mellitus. All the guidelines must be followed while performing self blood glucose monitoring and tracking of values is essential to facilitate the physician while titrating the drugs and /or doses of anti diabetes medication. Self titration by patients following self monitoring must be discouraged. To assess the knowledge and practice of self blood glucose monitoring among diabetes patients and extent of self titration of anti diabetes medicines among diabetes patients based on self blood glucose monitoring. This pilot, cross-sectional, observational study was conducted using a validated questionnaire among adult male and female diabetes patients performing self blood glucose monitoring at home. Diabetes patients with complications and juvenile diabetes patients were excluded. Out of 153 patients surveyed, only 37 (24.1%) (20 males, 17 females) patients were aware and have been following self blood glucose monitoring appropriately. About 116 (75.8%) (64 males, 52 females) of patients were devoid of adequate knowledge and did not practice self blood glucose monitoring in a proper way. Ninety eight (64.05%) accepted that they self titrate their anti diabetic medicines based on self monitoring. Self monitoring of blood glucose should be encouraged and patients should be taught importance of following correct steps and tracking of self monitoring by physician or diabetes educator.

Control Circuit For Two Stepping Motors

NASA Technical Reports Server (NTRS)

Ratliff, Roger; Rehmann, Kenneth; Backus, Charles

1990-01-01

Control circuit operates two independent stepping motors, one at a time. Provides following operating features: After selected motor stepped to chosen position, power turned off to reduce dissipation; Includes two up/down counters that remember at which one of eight steps each motor set. For selected motor, step indicated by illumination of one of eight light-emitting diodes (LED's) in ring; Selected motor advanced one step at time or repeatedly at rate controlled; Motor current - 30 mA at 90 degree positions, 60 mA at 45 degree positions - indicated by high or low intensity of LED that serves as motor-current monitor; Power-on reset feature provides trouble-free starts; To maintain synchronism between control circuit and motors, stepping of counters inhibited when motor power turned off.

Flow cytometry for enrichment and titration in massively parallel DNA sequencing

PubMed Central

Sandberg, Julia; Ståhl, Patrik L.; Ahmadian, Afshin; Bjursell, Magnus K.; Lundeberg, Joakim

2009-01-01

Massively parallel DNA sequencing is revolutionizing genomics research throughout the life sciences. However, the reagent costs and labor requirements in current sequencing protocols are still substantial, although improvements are continuously being made. Here, we demonstrate an effective alternative to existing sample titration protocols for the Roche/454 system using Fluorescence Activated Cell Sorting (FACS) technology to determine the optimal DNA-to-bead ratio prior to large-scale sequencing. Our method, which eliminates the need for the costly pilot sequencing of samples during titration is capable of rapidly providing accurate DNA-to-bead ratios that are not biased by the quantification and sedimentation steps included in current protocols. Moreover, we demonstrate that FACS sorting can be readily used to highly enrich fractions of beads carrying template DNA, with near total elimination of empty beads and no downstream sacrifice of DNA sequencing quality. Automated enrichment by FACS is a simple approach to obtain pure samples for bead-based sequencing systems, and offers an efficient, low-cost alternative to current enrichment protocols. PMID:19304748

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.

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.

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.

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.

Quality assessment of tomato landraces and virus-resistant breeding lines: quick estimation by near infrared reflectance spectroscopy.

PubMed

García-Martínez, Santiago; Gálvez-Sola, Luis N; Alonso, Arantxa; Agulló, Enrique; Rubio, Fernando; Ruiz, Juan J; Moral, Raúl

2012-04-01

Several tomato landraces are very popular in south-eastern Spain for their organoleptic fruit quality, but these cultivars are highly susceptible to several viruses. A breeding programme is being carried out for the introduction of virus resistances into these landraces. In the last steps of our breeding programme a high number of breeding lines must be evaluated for agronomic and organoleptic quality parameters. Near infrared reflectance spectroscopy (NIRS) technology shows considerable promise and is ideally suited to the requirements of breeders. Significant differences between a set of 35 tomato breeding lines, seven landraces and one commercial hybrid were observed for quality and mineral content parameters, suggesting that there are considerable levels of genetic diversity between the cultivar groups studied. Using NIRS on dry samples of tomato constitutes a feasible technique to estimate the content of several minerals (C, N, P, K, Ca, Na, Mn, Mg and Cu) according to the coefficient of determination for calibration (R(2) > 0.90). NIRS estimations of soluble solids content and titratable acidity obtained were considered useful only for general screening purposes. NIRS technology may be a useful tool in the selection of lines coming out of tomato breeding programs, allowing a quick estimation of mineral content. However, the estimation of soluble solids content and titratable acidity by NIRS must be improved. Copyright © 2011 Society of Chemical Industry.

Tracking Equilibrium and Nonequilibrium Shifts in Data with TREND.

PubMed

Xu, Jia; Van Doren, Steven R

2017-01-24

Principal component analysis (PCA) discovers patterns in multivariate data that include spectra, microscopy, and other biophysical measurements. Direct application of PCA to crowded spectra, images, and movies (without selecting peaks or features) was shown recently to identify their equilibrium or temporal changes. To enable the community to utilize these capabilities with a wide range of measurements, we have developed multiplatform software named TREND to Track Equilibrium and Nonequilibrium population shifts among two-dimensional Data frames. TREND can also carry this out by independent component analysis. We highlight a few examples of finding concurrent processes. TREND extracts dual phases of binding to two sites directly from the NMR spectra of the titrations. In a cardiac movie from magnetic resonance imaging, TREND resolves principal components (PCs) representing breathing and the cardiac cycle. TREND can also reconstruct the series of measurements from selected PCs, as illustrated for a biphasic, NMR-detected titration and the cardiac MRI movie. Fidelity of reconstruction of series of NMR spectra or images requires more PCs than needed to plot the largest population shifts. TREND reads spectra from many spectroscopies in the most common formats (JCAMP-DX and NMR) and multiple movie formats. The TREND package thus provides convenient tools to resolve the processes recorded by diverse biophysical methods. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

Digital movie-based on automatic titrations.

PubMed

Lima, Ricardo Alexandre C; Almeida, Luciano F; Lyra, Wellington S; Siqueira, Lucas A; Gaião, Edvaldo N; Paiva Junior, Sérgio S L; Lima, Rafaela L F C

2016-01-15

This study proposes the use of digital movies (DMs) in a flow-batch analyzer (FBA) to perform automatic, fast and accurate titrations. The term used for this process is "Digital movie-based on automatic titrations" (DMB-AT). A webcam records the DM during the addition of the titrant to the mixing chamber (MC). While the DM is recorded, it is decompiled into frames ordered sequentially at a constant rate of 26 frames per second (FPS). The first frame is used as a reference to define the region of interest (ROI) of 28×13pixels and the R, G and B values, which are used to calculate the Hue (H) values for each frame. The Pearson's correlation coefficient (r) is calculated between the H values of the initial frame and each subsequent frame. The titration curves are plotted in real time using the r values and the opening time of the titrant valve. The end point is estimated by the second derivative method. A software written in C language manages all analytical steps and data treatment in real time. The feasibility of the method was attested by application in acid/base test samples and edible oils. Results were compared with classical titration and did not present statistically significant differences when the paired t-test at the 95% confidence level was applied. The proposed method is able to process about 117-128 samples per hour for the test and edible oil samples, respectively, and its precision was confirmed by overall relative standard deviation (RSD) values, always less than 1.0%. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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

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

Evidence of a two-step process and pathway dependency in the thermodynamics of poly(diallyldimethylammonium chloride)/poly(sodium acrylate) complexation.

PubMed

Vitorazi, L; Ould-Moussa, N; Sekar, S; Fresnais, J; Loh, W; Chapel, J-P; Berret, J-F

2014-12-21

Recent studies have pointed out the importance of polyelectrolyte assembly in the elaboration of innovative nanomaterials. Beyond their structures, many important questions on the thermodynamics of association remain unanswered. Here, we investigate the complexation between poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium acrylate) (PANa) chains using a combination of three techniques: isothermal titration calorimetry (ITC), static and dynamic light scattering and electrophoresis. Upon addition of PDADMAC to PANa or vice-versa, the results obtained by the different techniques agree well with each other, and reveal a two-step process. The primary process is the formation of highly charged polyelectrolyte complexes of size 100 nm. The secondary process is the transition towards a coacervate phase made of rich and poor polymer droplets. The binding isotherms measured are accounted for using a phenomenological model that provides the thermodynamic parameters for each reaction. Small positive enthalpies and large positive entropies consistent with a counterion release scenario are found throughout this study. Furthermore, this work stresses the importance of the underestimated formulation pathway or mixing order in polyelectrolyte complexation.

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.

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.

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.

Isolation of the Copper Redox Steps in the Standard Selective Catalytic Reduction on Cu-SSZ-13

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

Paolucci, Christopher; Verma, Anuj A.; Bates, Shane A.

2014-10-27

Operando X-ray absorption experiments and density functional theory (DFT) calculations are reported that elucidate the role of copper redox chemistry in the selective catalytic reduction (SCR) of NO over Cu-exchanged SSZ-13. Catalysts prepared to contain only isolated, exchanged CuII ions evidence both CuII and CuI ions under standard SCR conditions at 473 K. Reactant cutoff experiments show that NO and NH3 together are necessary for CuII reduction to CuI. DFT calculations show that NO-assisted NH3 dissociation is both energetically favorable and accounts for the observed CuII reduction. The calculations predict in situ generation of Brønsted sites proximal to CuI uponmore » reduction, which we quantify in separate titration experiments. Both NO and O2 are necessary for oxidation of CuI to CuII, which DFT suggests to occur by a NO2 intermediate. Reaction of Cu-bound NO2 with proximal NH4 + completes the catalytic cycle. N2 is produced in both reduction and oxidation half-cycles.« less

Isolation of the Copper Redox Steps in the Standard Selective Catalytic Reduction on Cu-SSZ-13

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

Paolucci, Christopher; Verma, Anuj A.; Bates, Shane A.

2014-09-12

Operando X-ray absorption experiments and density functional theory (DFT) calculations are reported that elucidate the role of copper redox chemistry in the selective catalytic reduction (SCR) of NO over Cu-exchanged SSZ-13. Catalysts prepared to contain only isolated, exchanged CuII ions evidence both CuII and CuI ions under standard SCR conditions at 473 K. Reactant cutoff experiments show that NO and NH3 together are necessary for CuII reduction to CuI. DFT calculations show that NO-assisted NH3 dissociation is both energetically favorable and accounts for the observed CuII reduction. The calculations predict in situ generation of Brønsted sites proximal to CuI uponmore » reduction, which we quantify in separate titration experiments. Both NO and O2 are necessary for oxidation of CuI to CuII, which DFT suggests to occur by a NO2 intermediate. Reaction of Cu-bound NO2 with proximal NH4 + completes the catalytic cycle. N2 is produced in both reduction and oxidation half-cycles.« less

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.

Titration-based screening for evaluation of natural product extracts: identification of an aspulvinone family of luciferase inhibitors

PubMed Central

Cruz, Patricia G.; Auld, Douglas S.; Schultz, Pamela J.; Lovell, Scott; Battaile, Kevin P.; MacArthur, Ryan; Shen, Min; Tamayo-Castillo, Giselle; Inglese, James; Sherman, David H.

2011-01-01

The chemical diversity of nature has tremendous potential for discovery of new molecular probes and medicinal agents. However, sensitivity of HTS assays to interfering components of crude extracts derived from plants, macro- and microorganisms has curtailed their use in lead discovery efforts. Here we describe a process for leveraging the concentration-response curves (CRCs) obtained from quantitative HTS to improve the initial selection of “actives” from a library of partially fractionated natural product extracts derived from marine actinomycetes and fungi. By using pharmacological activity, the first-pass CRC paradigm aims to improve the probability that labor-intensive subsequent steps of re-culturing, extraction and bioassay-guided isolation of active component(s) target the most promising strains and growth conditions. We illustrate how this process identified a family of fungal metabolites as potent inhibitors of firefly luciferase, subsequently resolved in molecular detail by x-ray crystallography. PMID:22118678

Titration-based screening for evaluation of natural product extracts: identification of an aspulvinone family of luciferase inhibitors

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

Cruz, P.G.; Auld, D.S.; Schultz, P.J.

2011-11-28

The chemical diversity of nature has tremendous potential for the discovery of molecular probes and medicinal agents. However, sensitivity of HTS assays to interfering components of crude extracts derived from plants, and macro- and microorganisms has curtailed their use in lead discovery. Here, we describe a process for leveraging the concentration-response curves obtained from quantitative HTS to improve the initial selection of actives from a library of partially fractionated natural product extracts derived from marine actinomycetes and fungi. By using pharmacological activity, the first-pass CRC paradigm improves the probability that labor-intensive subsequent steps of reculturing, extraction, and bioassay-guided isolation ofmore » active component(s) target the most promising strains and growth conditions. We illustrate how this process identified a family of fungal metabolites as potent inhibitors of firefly luciferase, subsequently resolved in molecular detail by X-ray crystallography.« less

Kinetic properties of two Rhizopus exo-polygalacturonase enzymes hydrolyzing galacturonic acid oligomers using isothermal titration calorimetry

USDA-ARS?s Scientific Manuscript database

The kinetic characteristics of two Rhizopus oryzae exo-polygalacturonases acting on galacturonic acid oligomers (GalpA) were determined using isothermal titration calorimetry (ITC). RPG15 hydrolyzing (GalpA)2 demonstrated a Km of 55 uM and kcat of 10.3 s^-1^ while RPG16 was shown to have greater af...

Using Spreadsheets to Produce Acid-Base Titration Curves.

ERIC Educational Resources Information Center

Cawley, Martin James; Parkinson, John

1995-01-01

Describes two spreadsheets for producing acid-base titration curves, one uses relatively simple cell formulae that can be written into the spreadsheet by inexperienced students and the second uses more complex formulae that are best written by the teacher. (JRH)

Determination of iodide with 1,3-dibromo-5,5-dimethylhydantoin (DBH) in comparison with the ICl-method. Analytical methods of pharmacopeias with DBH in respect to environmental and economical concern. Part 3.

PubMed

Hilp, M; Senjuk, S

2001-06-01

USP 1995 (The United States Pharmacopeia, 23rd Edit., (1995), potassium iodide p. 1265, sodium iodide p. 1424), PH. EUR. 1997 (European Pharmacopoeia, third ed., Council of Europe, Strasbourg, (1997), potassium iodide p. 1367, sodium iodide p. 1493) and JAP 1996 (The Japanes Pharmacopoeia, 13th ed. (1996), potassium iodide p. 578, sodium iodide p. 630) determine iodide with the ICl-method (J. Am. Chem. Soc. 25 (1903) 756-761; Z. Anorg. Chem. 36 (1903) 76-83; Fresenius Z. Anal. Chem. 106 (1936) 12-23; Arzneibuch-Kommentar, Wissenschaftliche Erläuterungen zum Europäischen Arzneibuch, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, Govi-Verlag - Pharmazeutischer Verlag GmbH, Eschborn, 12th suppl. (1999), K10 p. 2), using chloroform, which is toxic and hazardous to environment. Without the application of chlorinated hydrocarbons USP 2000 (The United State Pharmacopeia, 24th ed. (2000), potassium iodide p. 1368, sodium iodide p. 1535) and Brit 1999 (British Pharmacopoeia London, (1999), Appendix VIII C, p. A162) titrate iodide with the redox indicator amaranth. A titration with potentiometric indication giving two end-points at the step of I(2) and [ICl(2)](-) is described. Due to the high concentration of hydrochloric acid required for the ICl-method, the determination with DBH (1,3-dibromo-5,5-dimethylhydantoin; 1,3-dibromo-5,5-dimethyl-2,4-imidazolidinedione) can be recommended and is performed easily. Similarly, the iodide content of gallamine triethiodide may be analyzed with DBH by application of a visual two-phase titration in water and ethyl acetate or with potentiometric indication in a mixture of 2-propanol and water. During the removal of the excess of DBH 4-bromo-triethylgallamine (2,2',2"-[1-bromo-benzene-2,3,4-triyltris(oxy)]N,N,N-triethylethanium) is formed.

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

Zarzycki, Piotr P.; Rosso, Kevin M.

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 non-uniformity, 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 do not necessarily need to bemore » 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 non-uniformity, 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.« less

An original method for producing acetaldehyde and diacetyl by yeast fermentation.

PubMed

Rosca, Irina; Petrovici, Anca Roxana; Brebu, Mihai; Stoica, Irina; Minea, Bogdan; Marangoci, Narcisa

In this study a natural culture medium that mimics the synthetic yeast peptone glucose medium used for yeast fermentations was designed to screen and select yeasts capable of producing high levels of diacetyl and acetaldehyde. The presence of whey powder and sodium citrate in the medium along with manganese and magnesium sulfate enhanced both biomass and aroma development. A total of 52 yeasts strains were cultivated in two different culture media, namely, yeast peptone glucose medium and yeast acetaldehyde-diacetyl medium. The initial screening of the strains was based on the qualitative reaction of the acetaldehyde with Schiff's reagent (violet color) and diacetyl with Brady's reagent (yellow precipitate). The fermented culture media of 10 yeast strains were subsequently analyzed by gas chromatography to quantify the concentration of acetaldehyde and diacetyl synthesized. Total titratable acidity values indicated that a total titratable acidity of 5.5°SH, implying culture medium at basic pH, was more favorable for the acetaldehyde biosynthesis using strain D15 (Candida lipolytica; 96.05mgL -1 acetaldehyde) while a total titratable acidity value of 7°SH facilitated diacetyl flavor synthesis by strain D38 (Candida globosa; 3.58mgL -1 diacetyl). Importantly, the results presented here suggest that this can be potentially used in the baking industry. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

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.

Development of new composite biosorbents from olive pomace wastes

NASA Astrophysics Data System (ADS)

Pagnanelli, Francesca; Viggi, Carolina Cruz; Toro, Luigi

2010-06-01

In this study olive pomace was used as a source of binding substances for the development of composite biosorbents to be used in heavy metal removal from aqueous solutions. The aim was to obtain biosorbent material with an increased concentration of binding sites. The effects of two different extraction procedures (one using only methanol and the other one hexane followed by methanol) on the binding properties of olive pomace were tested by potentiometric titrations and batch biosorption tests for copper and cadmium removal. Titration modelling evidenced that both kinds of extractions generated a solid with a reduced amount of protonatable sites. Biosorption tests were organized according to full factorial designs. Analysis of variance denoted that both kinds of extractions determined a statistically significant negative effect on metal biosorption. In the case of cadmium extractions also determined a significant decrease of selectivity with respect to olive pomace. When the acid-base and binding properties of the substances extracted were determined, they were adsorbed onto a synthetic resin (octadecylsilane) and calcium alginate beads. In this way two kinds of composite biosorbents have been obtained both having an increased concentration of binding substances with respect to native olive pomace, also working more efficiently in metal removal.

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

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.

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.

Effect of Spatial Titration on Task Performance

ERIC Educational Resources Information Center

Glowacki, Lawrence

1976-01-01

A reinforcement schedule and spatial titration method were used to determine task-reinforcement area separation most preferred and effective in two third-grade boys. Errors in task performance decreased task-reinforcement area separation, while correct responses in task performance increased task-reinforcement area separation. (Author)

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.

One-Step and Two-Step Facility Acquisition for Military Construction: Project Selection and Implementation Procedures

DTIC Science & Technology

1990-08-01

the guidance in this report. 1-4. Scope This guidance covers selection of projects suitable for a One-Step or Two-Step approach, development of design...conducted, focus on resolving proposal deficiencies; prices are not "negotiated" in the common use of the term. A Request for Proposal (RFP) states project ...carefully examines experience and past performance in the design of similar projects and building types. Quality of

AMDTreat 5.0+ with PHREEQC titration module to compute caustic chemical quantity, effluent quality, and sludge volume

USGS Publications Warehouse

Cravotta, Charles A.; Means, Brent P; Arthur, Willam; McKenzie, Robert M; Parkhurst, David L.

2015-01-01

Alkaline chemicals are commonly added to discharges from coal mines to increase pH and decrease concentrations of acidity and dissolved aluminum, iron, manganese, and associated metals. The annual cost of chemical treatment depends on the type and quantities of chemicals added and sludge produced. The AMDTreat computer program, initially developed in 2003, is widely used to compute such costs on the basis of the user-specified flow rate and water quality data for the untreated AMD. Although AMDTreat can use results of empirical titration of net-acidic or net-alkaline effluent with caustic chemicals to accurately estimate costs for treatment, such empirical data are rarely available. A titration simulation module using the geochemical program PHREEQC has been incorporated with AMDTreat 5.0+ to improve the capability of AMDTreat to estimate: (1) the quantity and cost of caustic chemicals to attain a target pH, (2) the chemical composition of the treated effluent, and (3) the volume of sludge produced by the treatment. The simulated titration results for selected caustic chemicals (NaOH, CaO, Ca(OH)2, Na2CO3, or NH3) without aeration or with pre-aeration can be compared with or used in place of empirical titration data to estimate chemical quantities, treated effluent composition, sludge volume (precipitated metals plus unreacted chemical), and associated treatment costs. This paper describes the development, evaluation, and potential utilization of the PHREEQC titration module with the new AMDTreat 5.0+ computer program available at http://www.amd.osmre.gov/.

Deconvolutions based on singular value decomposition and the pseudoinverse: a guide for beginners.

PubMed

Hendler, R W; Shrager, R I

1994-01-01

Singular value decomposition (SVD) is deeply rooted in the theory of linear algebra, and because of this is not readily understood by a large group of researchers who could profit from its application. In this paper, we discuss the subject on a level that should be understandable to scientists who are not well versed in linear algebra. However, because it is necessary that certain key concepts in linear algebra be appreciated in order to comprehend what is accomplished by SVD, we present the section, 'Bare basics of linear algebra'. This is followed by a discussion of the theory of SVD. Next we present step-by-step examples to illustrate how SVD is applied to deconvolute a titration involving a mixture of three pH indicators. One noiseless case is presented as well as two cases where either a fixed or varying noise level is present. Finally, we discuss additional deconvolutions of mixed spectra based on the use of the pseudoinverse.

Subsite binding energies of an exo-polygalacturonase using isothermal titration calorimetry

USDA-ARS?s Scientific Manuscript database

Thermodynamic parameters for binding of a series of galacturonic acid oligomers to an exo-polygalacturonase, RPG16 from Rhizopus oryzae, were determined by isothermal titration calorimetry. Binding of oligomers varying in chain length from two to five galacturonic acid residues is an exothermic proc...

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.

Development of a Platform to Enable Fully Automated Cross-Titration Experiments.

PubMed

Cassaday, Jason; Finley, Michael; Squadroni, Brian; Jezequel-Sur, Sylvie; Rauch, Albert; Gajera, Bharti; Uebele, Victor; Hermes, Jeffrey; Zuck, Paul

2017-04-01

In the triage of hits from a high-throughput screening campaign or during the optimization of a lead compound, it is relatively routine to test compounds at multiple concentrations to determine potency and maximal effect. Additional follow-up experiments, such as agonist shift, can be quite valuable in ascertaining compound mechanism of action (MOA). However, these experiments require cross-titration of a test compound with the activating ligand of the receptor requiring 100-200 data points, severely limiting the number tested in MOA assays in a screening triage. We describe a process to enhance the throughput of such cross-titration experiments through the integration of Hewlett Packard's D300 digital dispenser onto one of our robotics platforms to enable on-the-fly cross-titration of compounds in a 1536-well plate format. The process handles all the compound management and data tracking, as well as the biological assay. The process relies heavily on in-house-built software and hardware, and uses our proprietary control software for the platform. Using this system, we were able to automate the cross-titration of compounds for both positive and negative allosteric modulators of two different G protein-coupled receptors (GPCRs) using two distinct assay detection formats, IP1 and Ca 2+ detection, on nearly 100 compounds for each target.

A modified two-point titration method for the determination of volatile fatty acids in anaerobic systems.

PubMed

Mu, Zhe-Xuan; He, Chuan-Shu; Jiang, Jian-Kai; Zhang, Jie; Yang, Hou-Yun; Mu, Yang

2018-08-01

The volatile fatty acids (VFA) concentration plays important roles in the rapid start-up and stable operation of anaerobic reactors. It's essential to develop a simple and accurate method to monitor the VFA concentration in the anaerobic systems. In present work, a modified two-point titration method was developed to determine the VFA concentration. The results show that VFA concentration in standard solutions estimated by the titration method coincided well with that measured by gas chromatograph, where all relative errors were lower than 5.5%. Compared with the phosphate, ammonium and sulfide subsystems, the effect of bicarbonate on the accuracy of the developed method was relatively significant. When the bicarbonate concentration varied from 0 to 8 mmol/L, the relative errors increased from 1.2% to 30% for VFA concentration at 1 mmol/L, but were within 2.0% for that at 5 mmol/L. In addition, the VFA composition affected the accuracy of the titration method to some extent. This developed titration method was further proved to be effective with practical effluents from a lab-scale anaerobic reactor under organic shock loadings and an unstable full-scale anaerobic reactor. Copyright © 2018 Elsevier Ltd. All rights reserved.

Glycemic penalty index for adequately assessing and comparing different blood glucose control algorithms

PubMed Central

Van Herpe, Tom; De Brabanter, Jos; Beullens, Martine; De Moor, Bart; Van den Berghe, Greet

2008-01-01

Introduction Blood glucose (BG) control performed by intensive care unit (ICU) nurses is becoming standard practice for critically ill patients. New (semi-automated) 'BG control' algorithms (or 'insulin titration' algorithms) are under development, but these require stringent validation before they can replace the currently used algorithms. Existing methods for objectively comparing different insulin titration algorithms show weaknesses. In the current study, a new approach for appropriately assessing the adequacy of different algorithms is proposed. Methods Two ICU patient populations (with different baseline characteristics) were studied, both treated with a similar 'nurse-driven' insulin titration algorithm targeting BG levels of 80 to 110 mg/dl. A new method for objectively evaluating BG deviations from normoglycemia was founded on a smooth penalty function. Next, the performance of this new evaluation tool was compared with the current standard assessment methods, on an individual as well as a population basis. Finally, the impact of four selected parameters (the average BG sampling frequency, the duration of algorithm application, the severity of disease, and the type of illness) on the performance of an insulin titration algorithm was determined by multiple regression analysis. Results The glycemic penalty index (GPI) was proposed as a tool for assessing the overall glycemic control behavior in ICU patients. The GPI of a patient is the average of all penalties that are individually assigned to each measured BG value based on the optimized smooth penalty function. The computation of this index returns a number between 0 (no penalty) and 100 (the highest penalty). For some patients, the assessment of the BG control behavior using the traditional standard evaluation methods was different from the evaluation with GPI. Two parameters were found to have a significant impact on GPI: the BG sampling frequency and the duration of algorithm application. A higher BG sampling frequency and a longer algorithm application duration resulted in an apparently better performance, as indicated by a lower GPI. Conclusion The GPI is an alternative method for evaluating the performance of BG control algorithms. The blood glucose sampling frequency and the duration of algorithm application should be similar when comparing algorithms. PMID:18302732

Binding Selectivity of Methanobactin from Methylosinus trichosporium OB3b for Copper(I), Silver(I), Zinc(II), Nickel(II), Cobalt(II), Manganese(II), Lead(II), and Iron(II)

NASA Astrophysics Data System (ADS)

McCabe, Jacob W.; Vangala, Rajpal; Angel, Laurence A.

2017-12-01

Methanobactin (Mb) from Methylosinus trichosporium OB3b is a member of a class of metal binding peptides identified in methanotrophic bacteria. Mb will selectively bind and reduce Cu(II) to Cu(I), and is thought to mediate the acquisition of the copper cofactor for the enzyme methane monooxygenase. These copper chelating properties of Mb make it potentially useful as a chelating agent for treatment of diseases where copper plays a role including Wilson's disease, cancers, and neurodegenerative diseases. Utilizing traveling wave ion mobility-mass spectrometry (TWIMS), the competition for the Mb copper binding site from Ag(I), Pb(II), Co(II), Fe(II), Mn(II), Ni(II), and Zn(II) has been determined by a series of metal ion titrations, pH titrations, and metal ion displacement titrations. The TWIMS analyses allowed for the explicit identification and quantification of all the individual Mb species present during the titrations and measured their collision cross-sections and collision-induced dissociation patterns. The results showed Ag(I) and Ni(II) could irreversibly bind to Mb and not be effectively displaced by Cu(I), whereas Ag(I) could also partially displace Cu(I) from the Mb complex. At pH ≈ 6.5, the Mb binding selectivity follows the order Ag(I)≈Cu(I)>Ni(II)≈Zn(II)>Co(II)>>Mn(II)≈Pb(II)>Fe(II), and at pH 7.5 to 10.4 the order is Ag(I)>Cu(I)>Ni(II)>Co(II)>Zn(II)>Mn(II)≈Pb(II)>Fe(II). Breakdown curves of the disulfide reduced Cu(I) and Ag(I) complexes showed a correlation existed between their relative stability and their compact folded structure indicated by their CCS. Fluorescence spectroscopy, which allowed the determination of the binding constant, compared well with the TWIMS analyses, with the exception of the Ni(II) complex. [Figure not available: see fulltext.

Binding Selectivity of Methanobactin from Methylosinus trichosporium OB3b for Copper(I), Silver(I), Zinc(II), Nickel(II), Cobalt(II), Manganese(II), Lead(II), and Iron(II).

PubMed

McCabe, Jacob W; Vangala, Rajpal; Angel, Laurence A

2017-12-01

Methanobactin (Mb) from Methylosinus trichosporium OB3b is a member of a class of metal binding peptides identified in methanotrophic bacteria. Mb will selectively bind and reduce Cu(II) to Cu(I), and is thought to mediate the acquisition of the copper cofactor for the enzyme methane monooxygenase. These copper chelating properties of Mb make it potentially useful as a chelating agent for treatment of diseases where copper plays a role including Wilson's disease, cancers, and neurodegenerative diseases. Utilizing traveling wave ion mobility-mass spectrometry (TWIMS), the competition for the Mb copper binding site from Ag(I), Pb(II), Co(II), Fe(II), Mn(II), Ni(II), and Zn(II) has been determined by a series of metal ion titrations, pH titrations, and metal ion displacement titrations. The TWIMS analyses allowed for the explicit identification and quantification of all the individual Mb species present during the titrations and measured their collision cross-sections and collision-induced dissociation patterns. The results showed Ag(I) and Ni(II) could irreversibly bind to Mb and not be effectively displaced by Cu(I), whereas Ag(I) could also partially displace Cu(I) from the Mb complex. At pH ≈ 6.5, the Mb binding selectivity follows the order Ag(I)≈Cu(I)>Ni(II)≈Zn(II)>Co(II)>Mn(II)≈Pb(II)>Fe(II), and at pH 7.5 to 10.4 the order is Ag(I)>Cu(I)>Ni(II)>Co(II)>Zn(II)>Mn(II)≈Pb(II)>Fe(II). Breakdown curves of the disulfide reduced Cu(I) and Ag(I) complexes showed a correlation existed between their relative stability and their compact folded structure indicated by their CCS. Fluorescence spectroscopy, which allowed the determination of the binding constant, compared well with the TWIMS analyses, with the exception of the Ni(II) complex. Graphical abstract ᅟ.

The binding of aluminum to mugineic acid and related compounds as studied by potentiometric titration.

PubMed

Yoshimura, Etsuro; Kohdr, Hicham; Mori, Satoshi; Hider, Robert C

2011-08-01

The phytosiderophores, mugineic acid (MA) and epi-hydroxymugineic acid (HMA), together with a related compound, nicotianamine (NA), were investigated for their ability to bind Al(III). Potentiometric titration analysis demonstrated that MA and HMA bind Al(III), in contrast to NA which does not under normal physiological conditions. With MA and HMA, in addition to the Al complex (AlL), the protonated (AlLH) and deprotonated (AlLH(-1)) complexes were identified from an analysis of titration curves, where L denotes the phytosiderophore form in which all the carboxylate functions are ionized. The equilibrium formation constants of the Al(III) phytosiderophore complexes are much smaller than those of the corresponding Fe(III) complexes. The higher selectivity of phytosiderophores for Fe(III) over Al(III) facilitates Fe(III) acquisition in alkaline conditions where free Al(III) levels are higher than free Fe(III) levels.

Determination of pKa values of new phenacyl-piperidine derivatives by potentiometric titration method in aqueous medium at room temperature (25±0.5oC).

PubMed

Zafar, Shaista; Akhtar, Shamim; Tariq, Talat; Mushtaq, Noushin; Akram, Arfa; Ahmed, Ahsaan; Arif, Muhammad; Naeem, Sabahat; Anwar, Sana

2014-07-01

Dissociation constant (pKa) of ten novel phenacyl derivatives of piperidine were determined by potentiometric titration method in aqueous medium at room temperature (25 ±0.5°C). The sample solutions were prepared in deionized water with ionic strength 0.01M and titrated with 0.1M NaOH solution. In addition, ΔG values were also calculated. Different prediction software programs were used to calculate pKa values too and compared to the experimentally observed pKa values. The experimental and theoretical values were found in close agreement. The results obtained in this research would help to predict the good absorption of the studied compounds and can be selected as lead molecules for the synthesis of CNS active agents because of their lipophilic nature especially compound VII.

Comparison of HPLC, UV spectrophotometry and potentiometric titration methods for the determination of lumefantrine in pharmaceutical products.

PubMed

da Costa César, Isabela; Nogueira, Fernando Henrique Andrade; Pianetti, Gérson Antônio

2008-09-10

This paper describes the development and evaluation of a HPLC, UV spectrophotometry and potentiometric titration methods to quantify lumefantrine in raw materials and tablets. HPLC analyses were carried out using a Symmetry C(18) column and a mobile phase composed of methanol and 0.05% trifluoroacetic acid (80:20), with a flow rate of 1.0ml/min and UV detection at 335nm. For the spectrophotometric analyses, methanol was used as solvent and the wavelength of 335nm was selected for the detection. Non-aqueous titration of lumefantrine was carried out using perchloric acid as titrant and glacial acetic acid/acetic anhydride as solvent. The end point was potentiometrically determined. The three evaluated methods showed to be adequate to quantify lumefantrine in raw materials, while HPLC and UV methods presented the most reliable results for the analyses of tablets.

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.

A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide.

PubMed

Setnik, Beatrice; Roland, Carl L; Sommerville, Kenneth W; Pixton, Glenn C; Berke, Robert; Calkins, Anne; Goli, Veeraindar

2015-01-01

To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN) using a standardized conversion guide. This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%). The mean (standard deviation) number of days to stable dose was 20 (8.94), and number of titration steps to stable dose was 2.4 (1.37). The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN.

A second dihydroorotate dehydrogenase (Type A) of the human pathogen Enterococcus faecalis: expression, purification, and steady-state kinetic mechanism.

PubMed

Marcinkeviciene, J; Jiang, W; Locke, G; Kopcho, L M; Rogers, M J; Copeland, R A

2000-05-01

We report the identification, expression, and characterization of a second Dihydroorotate dehydrogenase (DHODase A) from the human pathogen Enterococcus faecalis. The enzyme consists of a polypeptide chain of 322 amino acids that shares 68% identity with the cognate type A enzyme from the bacterium Lactococcus lactis. E. faecalis DHODase A catalyzed the oxidation of l-dihydroorotate while reducing a number of substrates, including fumarate, coenzyme Q(0), and menadione. The steady-state kinetic mechanism has been determined with menadione as an oxidizing substrate at pH 7.5. Initial velocity and product inhibition data suggest that the enzyme follows a two-site nonclassical ping-pong kinetic mechanism. The absorbance of the active site FMN cofactor is quenched in a concentration-dependent manner by titration with orotate and barbituric acid, two competitive inhibitors with respect to dihydroorotate. In contrast, titration of the enzyme with menadione had no effect on FMN absorbance, consistent with nonoverlapping binding sites for dihyroorotate and menadione, as suggested from the kinetic mechanism. The reductive half-reaction has been shown to be only partially rate limiting, and an attempt to evaluate the slow step in the overall reaction has been made by simulating orotate production under steady-state conditions. Our data indicate that the oxidative half-reaction is a rate-limiting segment, while orotate, most likely, retains significant affinity for the reduced enzyme, as suggested by the product inhibition pattern. Copyright 2000 Academic Press.

STEPS: A NARRATIVE ACCOUNT OF A GABAPENTIN SEEDING TRIAL

PubMed Central

Krumholz, Samuel D.; Egilman, David S.; Ross, Joseph S.

2012-01-01

Background Seeding trials, clinical studies conducted by pharmaceutical companies for marketing purposes, have rarely been described in detail. Methods We examined all documents relating to the clinical trial Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) produced during the Neurontin marketing, sales practices and product liability litigation, including company internal and external correspondence, reports, and presentations, as well as depositions elicited in legal proceedings of Harden Manufacturing v. Pfizer and Franklin v. Warner-Lambert, the majority of which were created between 1990 and 2009. Using a systematic search strategy, we identified and reviewed all documents related to the STEPS trial, in order to identify key themes related to the trial’s conduct and determine the extent of marketing involvement in its planning and implementation. Results Documents demonstrated that STEPS was a seeding trial posing as a legitimate scientific study. Documents consistently described the trial itself, not trial results, to be a marketing tactic in the company’s marketing plans. Documents demonstrated that several external sources questioned the validity of the study before execution, and that data quality during the study was often compromised. Furthermore, documents described company analyses examining the impact of participating as a STEPS investigator on rates and dosages of gabapentin prescribing, finding a positive association. None of these findings were reported in two published papers. Conclusions The STEPS trial was a seeding trial, used to promote gabapentin and increase prescribing among investigators, and marketing was extensively involved in its planning and implementation. PMID:21709111

A coumarin-pyrazolone based fluorescent probe for selective colorimetric and fluorimetric fluoride detection: Synthesis, spectroscopic properties and DFT calculations

NASA Astrophysics Data System (ADS)

Babür, Banu; Seferoğlu, Nurgül; Seferoğlu, Zeynel

2018-06-01

A novel coumarin based fluorescence anion chemosensor (P-1) bearing pyrazolone as a receptoric part was synthesized and characterized by using FT-IR, 1H/13C NMR and HRMS for the purpose of recognition of anions in DMSO. P-1 has four tautomeric structures and the most stable tautomeric form of P-1 was determined experimentally and theoretically. The chemosensor P-1 consists two receptoric parts as free amide Nsbnd H and enamine Nsbnd H which is stabilized intramolecular H-bonding with coumarin carbonyl oxygen. P-1 interacts selectively with fluoride anion via amide Nsbnd H. The selectivity and sensitivity of probe to various anions were determined with spectrophotometric and 1H NMR titration techniques as experimentally and all results were also explained by theoretical calculations.

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.

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.

Four points function fitted and first derivative procedure for determining the end points in potentiometric titration curves: statistical analysis and method comparison.

PubMed

Kholeif, S A

2001-06-01

A new method that belongs to the differential category for determining the end points from potentiometric titration curves is presented. It uses a preprocess to find first derivative values by fitting four data points in and around the region of inflection to a non-linear function, and then locate the end point, usually as a maximum or minimum, using an inverse parabolic interpolation procedure that has an analytical solution. The behavior and accuracy of the sigmoid and cumulative non-linear functions used are investigated against three factors. A statistical evaluation of the new method using linear least-squares method validation and multifactor data analysis are covered. The new method is generally applied to symmetrical and unsymmetrical potentiometric titration curves, and the end point is calculated using numerical procedures only. It outperforms the "parent" regular differential method in almost all factors levels and gives accurate results comparable to the true or estimated true end points. Calculated end points from selected experimental titration curves compatible with the equivalence point category of methods, such as Gran or Fortuin, are also compared with the new method.

Quantifying accessible sites and reactivity on titania–silica (photo)catalysts: Refining TOF calculations

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

Eaton, Todd R.; Campos, Michael P.; Gray, Kimberly A.

2014-01-01

It can be difficult to determine the number of active atoms accessible to the fluid phase in mixed oxide catalysts, as required for obtaining true turnover frequencies (TOF). Here, we utilize the selective titration of surface Ti atoms with phenylphosphonic acid (PPA) on TiO 2–SiO 2 materials to estimate the number of reactant-accessible sites. TiO 2–SiO 2 composites were synthesized over a range of Ti loadings from grafting of titanocene dichloride (Cp 2TiCl 2) or tetraethoxy orthotitanate (TEOT) on SiO 2 and sol–gel co-hydrolysis of Si and Ti alkoxides. The materials were characterized by DRUV–vis, XRD, BET, and XANES. Despitemore » the significant morphological and electronic differences, materials prepared by Cp 2TiCl 2 and TEOT yielded a near-constant TOF of 0.14 h -1 (±0.04) across Ti loadings, for benzyl alcohol photooxidation, when normalizing rates by sites titrated by PPA. The fraction of Ti atoms titrated by PPA was strongly dependent on synthesis method and surface density. PPA titration and benzyl alcohol photooxidation may be useful measures of surface accessibility in other supported oxides.« less

Antioxidative Categorization of Twenty Amino Acids Based on Experimental Evaluation.

PubMed

Xu, Naijin; Chen, Guanqun; Liu, Hui

2017-11-27

In view of the great importance bestowed on amino acids as antioxidants in oxidation resistance, we attempted two common redox titration methods in this report, including micro-potassium permanganate titration and iodometric titration, to measure the antioxidative capacity of 20 amino acids, which are the construction units of proteins in living organisms. Based on the relative intensities of the antioxidative capacity, we further conducted a quantitative comparison and found out that the product of experimental values obtained from the two methods was proven to be a better indicator for evaluating the relative antioxidative capacity of amino acids. The experimental results were largely in accordance with structural analysis made on amino acids. On the whole, the 20 amino acids concerned could be divided into two categories according to their antioxidative capacity. Seven amino acids, including tryptophan, methionine, histidine, lysine, cysteine, arginine and tyrosine, were greater in total antioxidative capacity compared with the other 13 amino acids.

A potentiometric titration method for the crystallization of drug-like organic molecules.

PubMed

Du-Cuny, Lei; Huwyler, Jörg; Fischer, Holger; Kansy, Manfred

2007-09-05

It is generally accepted, that crystalline solids representing a low energy polymorph should be selected for development of oral dosage forms. As a consequence, efficient and robust procedures are needed at an early stage during drug discovery to prepare crystals from drug-like organic molecules. In contrast to the use of supersaturated solutions, we present a potentiometric crystallization procedure where saturated solutions are prepared in a controlled manner by pH-titration. Crystallization is carried out under defined conditions using the sample concentration and experimental pK(a) values as input parameters. Crystals of high quality were obtained for 11 drugs selected to demonstrate the efficiency and applicability of the new method. Technical improvements are suggested to overcome practical limitations and to enhance the possibility of obtaining crystals from molecules in their uncharged form.

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

Time-Delayed Two-Step Selective Laser Photodamage of Dye-Biomolecule Complexes

NASA Astrophysics Data System (ADS)

Andreoni, A.; Cubeddu, R.; de Silvestri, S.; Laporta, P.; Svelto, O.

1980-08-01

A scheme is proposed for laser-selective photodamage of biological molecules, based on time-delayed two-step photoionization of a dye molecule bound to the biomolecule. The validity of the scheme is experimentally demonstrated in the case of the dye Proflavine, bound to synthetic polynucleotides.

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

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.

The selective V1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis

PubMed Central

Wiśniewska, Halina; Traber, Lillian D.; Lin, ChiiDean; Fan, Juanjuan; Hawkins, Hal K.; Cox, Robert A.; Wiśniewski, Kazimierz; Schteingart, Claudio D.; Landry, Donald W.; Rivière, Pierre J.-M.; Traber, Daniel L.

2014-01-01

Objective To determine if the selective vasopressin type 1a receptor (V1aR) agonist selepressin (FE 202158) is as effective as the mixed V1a/V2 receptor (V1aR/V2R) agonist vasopressor hormone arginine vasopressin (AVP) when used as a titrated first-line vasopressor therapy in an ovine model of Pseudomonas aeruginosa pneumonia-induced severe sepsis. Design Prospective, randomized, controlled laboratory experiment. Setting University animal research facility. Subjects Forty-five chronically instrumented sheep. Interventions Sheep were anesthetized, insufflated with cooled cotton smoke via tracheostomy, and P. aeruginosa were instilled into their airways. They were then placed on assisted ventilation, awakened, and resuscitated with lactated Ringer's solution titrated to maintain hematocrit ± 3% from baseline levels. If, despite fluid management, mean arterial pressure (MAP) fell by > 10 mm Hg from baseline levels, a continuous i.v. infusion of AVP or selepressin was titrated to raise and maintain MAP within 10 mm Hg of baseline. Effects of combination treatment of selepressin with the selective V2R agonist desmopressin were similarly investigated. Measurements and Main Results In septic sheep, MAP fell by ~30 mm Hg, systemic vascular resistance index (SVRI) decreased by ~50%, and ~7 L of fluid were retained over 24 h; this fluid accumulation was partially reduced by AVP and almost completely blocked by selepressin; combined infusion of selepressin and desmopressin increased fluid accumulation to levels similar to AVP treatment. Conclusions Resuscitation with the selective V1aR agonist selepressin blocked vascular leak more effectively than the mixed V1aR/V2R agonist AVP because of its lack of agonist activity at the V2R. PMID:24674922

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.

Interactions and encapsulation of vitamins C, B3, and B6 with dendrimers in water.

PubMed

Boisselier, Elodie; Liang, Liyuan; Dalko-Csiba, Maria; Ruiz, Jaime; Astruc, Didier

2010-05-25

Titrations of commercial diaminobutane (DAB) and polyamidoamine (PAMAM) dendrimers by vitamins C (ascorbic acid, AA), B(3) (nicotinic acid), and B(6) (pyridoxine) were monitored by (1)H NMR spectroscopy using the chemical shifts of both dendrimer and vitamin protons and analyzed by comparison with the titration of propylamine. Quaternarizations of the terminal primary amino groups and intradendritic tertiary amino groups, which are nearly quantitative with vitamin C, were characterized by more or less sharp variations (Deltadelta) of the (1)H chemical shift (delta) at the equivalence points. The peripheral primary amino groups of the DAB dendrimers were quaternarized first, but not selectively, whereas a sharp chemical-shift variation was recorded for the inner methylene protons near the tertiary amines, thereby indicating encapsulation, when all the dendritic amines were quaternarized. With DAB-G5-64-NH(2), some excess acid is required to protonate the inner amino groups, presumably because of basicity decrease due to excess charge repulsion. On the other hand, this selectivity was not observed with PAMAM dendrimers. The special case of the titration of the dendrimers by vitamin B(6) indicates only dominant supramolecular hydrogen-bonding interactions and no quaternarization, with core amino groups being privileged, which indicates the strong tendency to encapsulate vitamins. With vitamin B(3), a carboxylic acid, titration of DAB-G3-16-NH(2) shows that only six peripheral amino groups are protonated on average, even with excess vitamin B(3), because protonation is all the more difficult due to increased charge repulsion, as positive charges accumulate around the dendrimer. Inner amino groups interact with this vitamin, however, thus indicating encapsulation presumably with supramolecular hydrogen bonding without much charge transfer.

A Heckman selection model for the safety analysis of signalized intersections

PubMed Central

Wong, S. C.; Zhu, Feng; Pei, Xin; Huang, Helai; Liu, Youjun

2017-01-01

Purpose The objective of this paper is to provide a new method for estimating crash rate and severity simultaneously. Methods This study explores a Heckman selection model of the crash rate and severity simultaneously at different levels and a two-step procedure is used to investigate the crash rate and severity levels. The first step uses a probit regression model to determine the sample selection process, and the second step develops a multiple regression model to simultaneously evaluate the crash rate and severity for slight injury/kill or serious injury (KSI), respectively. The model uses 555 observations from 262 signalized intersections in the Hong Kong metropolitan area, integrated with information on the traffic flow, geometric road design, road environment, traffic control and any crashes that occurred during two years. Results The results of the proposed two-step Heckman selection model illustrate the necessity of different crash rates for different crash severity levels. Conclusions A comparison with the existing approaches suggests that the Heckman selection model offers an efficient and convenient alternative method for evaluating the safety performance at signalized intersections. PMID:28732050

Bis-ureidoquinoline as a selective fluoride anion sensor through hydrogen-bond interactions.

PubMed

Jo, Yunhee; Chidalla, Nagesh; Cho, Dong-Gyu

2014-10-03

Bis-ureidoquinoline shows a characteristic UV-vis absorbance and turn-on fluorescence changes in the presence of the fluoride anion. Such selective changes probably originate from the hydrogen-bond interactions, as shown by the (1)H NMR titration and DFT calculations. Bis-ureidoquinoline can be used as a fluoride-selective sensor for the detection of fluoride anions under illumination from a laboratory hand-held UV lamp.

Misoprostol versus antacid titration for preventing stress ulcers in postoperative surgical ICU patients.

PubMed Central

Zinner, M J; Rypins, E B; Martin, L R; Jonasson, O; Hoover, E L; Swab, E A; Fakouhi, T D

1989-01-01

Bleeding from gastroduodenal lesions is a potentially life-threatening complication in patients subjected to overwhelming physiologic stress. Titration of gastric contents with antacid was the first prophylactic treatment regimen proved to decrease the incidence of bleeding and remains the standard by which other methods are compared. We designed a prospective double-blind, double-placebo study comparing the effectiveness of antacid titration with fixed doses of a synthetic prostaglandin E1 analog (misoprostol) for preventing stress gastritis and bleeding. To assess the success of each treatment regimen, we did endoscopic examinations before operation, 72 hours after operation, and after the patient had completed the study. A total of 281 patients entered the study (140 misoprostol, 141 antacid). The two groups were comparable with respect to preoperative parameters and type of operation. We found no statistically significant differences between the two treatment groups concerning upper gastrointestinal tract lesions or serious adverse effects. No clinically evident upper gastrointestinal hemorrhage occurred in either group. Mean gastric pH, measured at two-hour intervals during the initial 72 hours, was maintained at 4.0 or higher in both groups. We conclude that fixed-dose misoprostol is as effective as intensive antacid titration in preventing stress ulcers and bleeding in surgical ICU patients. PMID:2510618

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

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.

Comparative study of titrated oral misoprostol solution and vaginal dinoprostone for labor induction at term pregnancy.

PubMed

Wang, Xiu; Yang, Aijun; Ma, Qingyong; Li, Xuelan; Qin, Li; He, Tongqiang

2016-09-01

To evaluate effectiveness and safety of titrated oral misoprostol solution (OMS) in comparison with vaginal dinoprostone for cervix ripening and labor induction in term pregnant women. A multicenter randomized controlled trial of women with term singleton pregnancy with indications for labor induction; 481 participants were allocated to receive titrated OMS with different doses by hourly administration according to the procedure or insert vaginal dinoprostone for cervix ripening and labor induction to compare maternal outcomes including indication of labor induction, mode of outcome of delivery, maternal morbidity, and neonatal outcomes between two groups for evaluating the efficacy and safety of titrated oral misoprostol induction. Proportion of delivery within 12 h of titrated oral misoprostol is significantly less than vaginal dinoprostone (p = 0.03), but no difference of total vaginal delivery rate (p = 0.93); the mean time of first treatment to vaginal delivery was longer in OMS group (21.3 ± 14.5 h) compared with the vaginal dinoprostone group (15.7 ± 9.6 h). Although the proportion of cesarean section between the two groups showed no statistically significant difference, OMS group showed significantly lower frequency of uterine hyperstimulation, hypertonus, partus precipitatus and non-reassuring fetal heart rate than dinoprostone group. Neonatal outcomes were similar evaluating from Apgar score and NICU admission. Our study also showed that labor induction of women with cervix Bishop score ≤3 needed increased dosage of misoprostol solution. Titrated OMS is as effective as vaginal dinoprostone in labor induction for term pregnant women, with safer effect for its lower rate of adverse effect for women.

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.

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.

Hydrogen Ion Buffering During Complete Brain Ischemia

PubMed Central

KRAIG, RICHARD P.; PULSINELLI, WILLIAM A.; PLUM, FRED

2011-01-01

As a first step to quantify [H+] changes in brain during ischemia we used H+-selective microelectrodes and enzyme fluorometric techniques to describe the relationship between interstitial [H+] ([H+]o) and peak tissue lactate after cardiac arrest. We found a step function relationship between [H+]o and tissue lactate rather than the linear titration expected in a homogeneous protein solution. Within a blood glucose range from 3–7 mM, brain lactate rose from 8–13 mmol/kg along with a rise in [H+]o of 99 ± 6 nM (0.44 ± 0.02 pH). At higher blood glucose levels (17–80 mM), brain lactate accumulated to levels of 16–31 mmol/kg; concurrently [H+]o rose by 608 ± 16 nM (1.07 ± 0.02 pH). The unchanging level of [H+]o between 8–13 and 16–31 mmol/kg lactate implies that [H+]o is at a steady-state, but not equilibrium with respect to [H+] in other brain compartments. We propose that ion-transport characteristics of astroglia account for the observed relationship of [H+]o to tissue lactate during complete ischemia and suggest that brain infarction develops after plasma membranes in brain cells can no longer transport ions to regulate [H+]. PMID:4041829

Uncertainty evaluation in the chloroquine phosphate potentiometric titration: application of three different approaches.

PubMed

Rodomonte, Andrea Luca; Montinaro, Annalisa; Bartolomei, Monica

2006-09-11

A measurement result cannot be properly interpreted if not accompanied by its uncertainty. Several methods to estimate uncertainty have been developed. From those methods three in particular were chosen in this work to estimate the uncertainty of the Eu. Ph. chloroquine phosphate assay, a potentiometric titration commonly used in medicinal control laboratories. The famous error-budget approach (also called bottom-up or step-by-step) described by the ISO Guide to the expression of Uncertainty in Measurement (GUM) was the first method chosen. It is based on the combination of uncertainty contributions that have to be directly derived from the measurement process. The second method employed was the Analytical Method Committee top-down which estimates uncertainty through reproducibility obtained during inter-laboratory studies. Data for its application were collected in a proficiency testing study carried out by over 50 laboratories throughout Europe. The last method chosen was the one proposed by Barwick and Ellison. It uses a combination of precision, trueness and ruggedness data to estimate uncertainty. These data were collected from a validation process specifically designed for uncertainty estimation. All the three approaches presented a distinctive set of advantages and drawbacks in their implementation. An expanded uncertainty of about 1% was assessed for the assay investigated.

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.

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.

Graphical evaluation of complexometric titration curves.

PubMed

Guinon, J L

1985-04-01

A graphical method, based on logarithmic concentration diagrams, for construction, without any calculations, of complexometric titration curves is examined. The titration curves obtained for different kinds of unidentate, bidentate and quadridentate ligands clearly show why only chelating ligands are usually used in titrimetric analysis. The method has also been applied to two practical cases where unidentate ligands are used: (a) the complexometric determination of mercury(II) with halides and (b) the determination of cyanide with silver, which involves both a complexation and a precipitation system; for this purpose construction of the diagrams for the HgCl(2)/HgCl(+)/Hg(2+) and Ag(CN)(2)(-)/AgCN/CN(-) systems is considered in detail.

Concentration-related response potentiometric titrations to study the interaction of small molecules with large biomolecules.

PubMed

Hamidi-Asl, Ezat; Daems, Devin; De Wael, Karolien; Van Camp, Guy; Nagels, Luc J

2014-12-16

In the present paper, the utility of a special potentiometric titration approach for recognition and calculation of biomolecule/small-molecule interactions is reported. This approach is fast, sensitive, reproducible, and inexpensive in comparison to the other methods for the determination of the association constant values (Ka) and the interaction energies (ΔG). The potentiometric titration measurement is based on the use of a classical polymeric membrane indicator electrode in a solution of the small-molecule ligand. The biomolecule is used as a titrant. The potential is measured versus a reference electrode and transformed into a concentration-related signal over the entire concentration interval, also at low concentrations, where the millivolt (y-axis) versus log canalyte (x-axis) potentiometric calibration curve is not linear. In the procedure, Ka is calculated for the interaction of cocaine with a cocaine binding aptamer and with an anticocaine antibody. To study the selectivity and cross-reactivity, other oligonucleotides and aptamers are tested, as well as other small ligand molecules such as tetrakis(4-chlorophenyl)borate, metergoline, lidocaine, and bromhexine. The calculated Ka compared favorably to the value reported in the literature using surface plasmon resonance. The potentiometric titration approach called "concentration-related response potentiometry" is used to study molecular interaction for seven macromolecular target molecules and four small-molecule ligands.

Potential benefits of slow titration of paroxetine treatment in an elderly population: eight-week results from a naturalistic setting.

PubMed

Gibiino, Sara; Mori, Elisa; De Ronchi, Diana; Serretti, Alessandro

2013-08-01

Late-life depression, often in association with anxiety, affects approximately 15% of individuals older than 65 years. Selective serotonin reuptake inhibitors are the first-line treatment but could be responsible of an early exacerbation of anxiety, possibly reduced by a very gradual titration of drugs. The main aim of this study is to compare gradual and rapid (standard) titration of paroxetine in an elderly population. In a naturalistic setting, 50 elderly (≥60 years old) outpatients with unipolar mood disorder or anxiety disorder were naturalistically assigned to abrupt initiation of 10 mg of paroxetine or to a gradual increase with 2.5 mg on alternate days up to 10 mg in 7 days. Then dosage could be maintained at 10 mg or increased according to clinical response. Primary outcome was efficacy as assessed by the Hamilton Depression Rating Scale (HAM-D) 21, HAM-D symptom subscales (core, psychic anxiety, somatic anxiety cluster), and Hamilton Anxiety Rating Scale changes. Secondary outcome was evaluation of overall dropouts at eighth week and evaluation of most common adverse effects through the global judgment of the Dosage Record and Treatment Emergent Symptom Scale. All data were recorded weekly for the first 8 weeks of treatment (with 1 more evaluation after 3 days from the baseline). Samples were comparable at baseline, with patients in gradual titration showing a higher level of psychic anxiety. During the first 3 days of treatment, a significant worsening in psychic anxiety was observed in patients treated abruptly with 10 mg of paroxetine (difference in HAM-D psychic anxiety subscale from baseline: 110.61% vs 89.38% with rapid and slow titration, respectively; t test P = 0.03). Overall, a significantly greater improvement in depressive and anxious symptoms favored gradual titration (HAM-D core cluster and HAM-D psychic anxiety cluster, respectively, P = 0.014 and P < 0.001, also when controlling for confounders). At the eighth week, significant higher dropouts in patients administered with abrupt dosage was observed (12.00% vs 40.91%, P = 0.02, respectively for slow and rapid titration). Our results suggest that a gradual titration of paroxetine could avoid the initial treatment anxiety worsening and dropout at the beginning of the treatment.

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…

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

Mishra, Arjun K.; Agnihotri, Pragati; Srivastava, Vijay Kumar

Highlights: • L. donovani spermidine synthase and S-adenosylmethionine decarboxylase have been cloned and purified. • S-adenosylmethionine decarboxylase has autocatalytic property. • GST pull down assay shows the two proteins to form a metabolon. • Isothermal titration calorimetry shows that binding was exothermic having K{sub d} value of 0.4 μM. • Interaction confirmed by fluorescence spectroscopy and size exclusion chromatography. - Abstract: Polyamine biosynthesis pathway has long been considered an essential drug target for trypanosomatids including Leishmania. S-adenosylmethionine decarboxylase (AdoMetDc) and spermidine synthase (SpdSyn) are enzymes of this pathway that catalyze successive steps, with the product of the former, decarboxylated S-adenosylmethioninemore » (dcSAM), acting as an aminopropyl donor for the latter enzyme. Here we have explored the possibility of and identified the protein–protein interaction between SpdSyn and AdoMetDc. The protein–protein interaction has been identified using GST pull down assay. Isothermal titration calorimetry reveals that the interaction is thermodynamically favorable. Fluorescence spectroscopy studies also confirms the interaction, with SpdSyn exhibiting a change in tertiary structure with increasing concentrations of AdoMetDc. Size exclusion chromatography suggests the presence of the complex as a hetero-oligomer. Taken together, these results suggest that the enzymes indeed form a heteromer. Computational analyses suggest that this complex differs significantly from the corresponding human complex, implying that this complex could be a better therapeutic target than the individual enzymes.« less

The importance of alcohol dehydrogenase in regulation of ethanol metabolism in rat liver cells.

PubMed Central

Page, R A; Kitson, K E; Hardman, M J

1991-01-01

We used titration with the inhibitors tetramethylene sulphoxide and isobutyramide to assess quantitatively the importance of alcohol dehydrogenase in regulation of ethanol oxidation in rat hepatocytes. In hepatocytes isolated from starved rats the apparent Flux Control Coefficient (calculated assuming a single-substrate irreversible reaction with non-competitive inhibition) of alcohol dehydrogenase is 0.3-0.5. Adjustment of this coefficient to allow for alcohol dehydrogenase being a two-substrate reversible enzyme increases the value by 1.3-1.4-fold. The final value of the Flux Control Coefficient of 0.5-0.7 indicates that alcohol dehydrogenase is a major rate-determining enzyme, but that other factors also have a regulatory role. In hepatocytes from fed rats the Flux Control Coefficient for alcohol dehydrogenase decreases with increasing acetaldehyde concentration. This suggests that, as acetaldehyde concentrations rise, control of the pathway shifts from alcohol dehydrogenase to other enzymes, particularly aldehyde dehydrogenase. There is not a single rate-determining step for the ethanol metabolism pathway and control is shared among several steps. PMID:1898355

Molecular Characterization of the Gas-Particle Interface of Soot Sampled from a Diesel Engine Using a Titration Method.

PubMed

Tapia, A; Salgado, M S; Martín, María Pilar; Lapuerta, M; Rodríguez-Fernández, J; Rossi, M J; Cabañas, B

2016-03-15

Surface functional groups of two different types of combustion aerosols, a conventional diesel (EN 590) and a hydrotreated vegetable oil (HVO) soot, have been investigated using heterogeneous chemistry (i.e., gas-particle surface reactions). A commercial sample of amorphous carbon (Printex XE2-B) was analyzed as a reference substrate. A Knudsen flow reactor was used to carry out the experiments under molecular flow conditions. The selected gases for the titration experiments were: N(CH3)3 for the identification of acidic sites, NH2OH for the presence of carbonyl groups, CF3COOH and HCl for basic sites of different strength, and O3 and NO2 for reducing groups. Reactivity with N(CH3)3 indicates a lower density of acidic functionalities for Printex XE2-B in relation to diesel and HVO soot. Results for NH2OH experiments indicates that commercial amorphous carbon exhibits a lower abundance of available carbonyl groups at the interface compared to the results from diesel and HVO soot, the latter being the one with the largest abundance of carbonyl functions. Reactions with acids indicate the presence of weak basic oxides on the particle surface that preferentially interact with the strong acid CF3COOH. Finally, reactions with O3 and NO2 reveal that diesel and especially HVO have a significantly higher reactivity with both oxidizers compared to that of Printex XE2-B because they have more reducing sites by roughly a factor of 10 and 30, respectively. The kinetics of titration reactions have also been investigated.

Constant-pH Hybrid Nonequilibrium Molecular Dynamics–Monte Carlo Simulation Method

PubMed Central

2016-01-01

A computational method is developed to carry out explicit solvent simulations of complex molecular systems under conditions of constant pH. In constant-pH simulations, preidentified ionizable sites are allowed to spontaneously protonate and deprotonate as a function of time in response to the environment and the imposed pH. The method, based on a hybrid scheme originally proposed by H. A. Stern (J. Chem. Phys.2007, 126, 164112), consists of carrying out short nonequilibrium molecular dynamics (neMD) switching trajectories to generate physically plausible configurations with changed protonation states that are subsequently accepted or rejected according to a Metropolis Monte Carlo (MC) criterion. To ensure microscopic detailed balance arising from such nonequilibrium switches, the atomic momenta are altered according to the symmetric two-ends momentum reversal prescription. To achieve higher efficiency, the original neMD–MC scheme is separated into two steps, reducing the need for generating a large number of unproductive and costly nonequilibrium trajectories. In the first step, the protonation state of a site is randomly attributed via a Metropolis MC process on the basis of an intrinsic pKa; an attempted nonequilibrium switch is generated only if this change in protonation state is accepted. This hybrid two-step inherent pKa neMD–MC simulation method is tested with single amino acids in solution (Asp, Glu, and His) and then applied to turkey ovomucoid third domain and hen egg-white lysozyme. Because of the simple linear increase in the computational cost relative to the number of titratable sites, the present method is naturally able to treat extremely large systems. PMID:26300709

Potentiometric sensors for the selective determination of sulbutiamine.

PubMed

Ahmed, M A; Elbeshlawy, M M

1999-11-01

Five novel polyvinyl chloride (PVC) matrix membrane sensors for the selective determination of sulbutiamine (SBA) cation are described. These sensors are based on molybdate, tetraphenylborate, reineckate, phosphotun gestate and phosphomolybdate, as possible ion-pairing agents. These sensors display rapid near-Nernstian stable response over a relatively wide concentration range 1x10(-2)-1x10(-6) M of sulbutiamine, with calibration slopes 28 32.6 mV decade(-1) over a reasonable pH range 2-6. The proposed sensors proved to have a good selectivity for SBA over some inorganic and organic cations. The five potentiometric sensors were applied successfully in the determination of SBA in a pharmaceutical preparation (arcalion-200) using both direct potentiometry and potentiometric titration. Direct potentiometric determination of microgram quantities of SBA gave average recoveries of 99.4 and 99.3 with mean standard deviation of 0.7 and 0.3 for pure SBA and arcalion-200 formulation respectively. Potentiometric titration of milligram quantities of SBA gave average recoveries of 99.3 and 98.7% with mean standard deviation of 0.7 and 1.2 for pure SBA and arcalion-200 formulation, respectively.

Competitive FRET-aptamer-based detection of methylphosphonic acid, a common nerve agent metabolite.

PubMed

Bruno, John G; Carrillo, Maria P; Phillips, Taylor; Vail, Neal K; Hanson, Douglas

2008-09-01

Competitive fluorescence resonance energy transfer (FRET)-aptamer-based assay formats are described for one-step detection of methylphosphonic acid (MPA; a metabolite of several organophosphorus (OP) nerve agents). AminoMPA was attached to tosyl-magnetic beads and used for DNA aptamer selection from which one dominant aptamer sequence emerged. Two different FRET approaches were attempted. In one approach, the complementary DNA sequence was used as a template for labeling the aptamer with Alexa Fluor 546 (AF 546)-14-dUTP by asymmetric PCR. Following 3-dimensional (3-D), molecular modeling of the aptamer-MPA complex, a series of three fluoresceinated aptamers labeled at positions 50, 51, and 52 in the putative optimal binding pocket were synthesized. In both FRET formats, aminoMPA was linked to Black Hole Quencher (BHQ-1 or BHQ-2)-succinimides and allowed to bind the fluorescein or AF 546-labeled MPA aptamer. Following gel filtration to purify the labeled MPA aptamer-BHQ-aminoMPA FRET complexes, the complexes were competed against various concentrations of unlabeled MPA, MPA derivatives, and unrelated compounds in titration and cross-reactivity studies. Both approaches yielded low microgram per milliliter detection limits for MPA with generally low levels of cross-reactivity for unrelated compounds. However, the data suggest a pattern of traits that may effect the direction (lights on or off) and intensity of the FRET.

tCRISPRi: tunable and reversible, one-step control of gene expression

NASA Astrophysics Data System (ADS)

Li, Xin-Tian; Jun, Yonggun; Erickstad, Michael J.; Brown, Steven D.; Parks, Adam; Court, Donald L.; Jun, Suckjoon

2016-12-01

The ability to control the level of gene expression is a major quest in biology. A widely used approach employs deletion of a nonessential gene of interest (knockout), or multi-step recombineering to move a gene of interest under a repressible promoter (knockdown). However, these genetic methods are laborious, and limited for quantitative study. Here, we report a tunable CRISPR-cas system, “tCRISPRi”, for precise and continuous titration of gene expression by more than 30-fold. Our tCRISPRi system employs various previous advancements into a single strain: (1) We constructed a new strain containing a tunable arabinose operon promoter PBAD to quantitatively control the expression of CRISPR-(d)Cas protein over two orders of magnitude in a plasmid-free system. (2) tCRISPRi is reversible, and gene expression is repressed under knockdown conditions. (3) tCRISPRi shows significantly less than 10% leaky expression. (4) Most important from a practical perspective, construction of tCRISPRi to target a new gene requires only one-step of oligo recombineering. Our results show that tCRISPRi, in combination with recombineering, provides a simple and easy-to-implement tool for gene expression control, and is ideally suited for construction of both individual strains and high-throughput tunable knockdown libraries.

Novel salicylic acid-oriented thiourea-type receptors as colorimetric chemosensor: Synthesis, characterizations and selective naked-eye recognition properties

NASA Astrophysics Data System (ADS)

Li, Shaowei; Cao, Xiufang; Chen, Changshui; Ke, Shaoyong

2012-10-01

Based on the salicylic acid backbone, three highly sensitive and selective colorimetric chemosensors with an acylthiourea binding unit have been designed, synthesized and characterized. These chemosensors have been utilized for selective recognition of fluoride anions in dry DMSO solution by typical spectroscopic titration techniques. Furthermore, the obtained chemosensors AR1-3 have shown naked-eye sensitivity for detection of biologically important fluoride ion over other anions in solution.

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.

Production of first generation adenoviral vectors for preclinical protocols: amplification, purification and functional titration.

PubMed

Armendáriz-Borunda, Juan; Bastidas-Ramírez, Blanca Estela; Sandoval-Rodríguez, Ana; González-Cuevas, Jaime; Gómez-Meda, Belinda; García-Bañuelos, Jesús

2011-11-01

Gene therapy represents a promising approach in the treatment of several diseases. Currently, the ideal vector has yet to be designed; though, adenoviral vectors (Ad-v) have provided the most utilized tool for gene transfer due principally to their simple production, among other specific characteristics. Ad-v viability represents a critical variable that may be affected by storage or shipping conditions and therefore it is advisable to be assessed previously to protocol performance. The present work is unique in this matter, as the complete detailed process to obtain Ad-v of preclinical grade is explained. Amplification in permissive HEK-293 cells, purification in CsCl gradients in a period of 10 h, spectrophotometric titration of viral particles (VP) and titration of infectious units (IU), yielding batches of AdβGal, AdGFP, AdHuPA and AdMMP8, of approximately 10¹³-10¹⁴ VP and 10¹²-10¹³ IU were carried out. In vivo functionality of therapeutic AdHuPA and AdMMP8 was evidenced in rats presenting CCl₄-induced fibrosis, as more than 60% of fibrosis was eliminated in livers after systemic delivery through iliac vein in comparison with irrelevant AdβGal. Time required to accomplish the whole Ad-v production steps, including IU titration was 20 to 30 days. We conclude that production of Ad-v following standard operating procedures assuring vector functionality and the possibility to effectively evaluate experimental gene therapy results, leaving aside the use of high-cost commercial kits or sophisticated instrumentation, can be performed in a conventional laboratory of cell culture. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Application of dead space fraction to titrate optimal positive end-expiratory pressure in an ARDS swine model.

PubMed

Bian, Weishuai; Chen, Wei; Chao, Yangong; Wang, Lan; Li, Liming; Guan, Jian; Zang, Xuefeng; Zhen, Jie; Sheng, Bo; Zhu, Xi

2017-04-01

This study aimed to apply the dead space fraction [ratio of dead space to tidal volume (VD/VT)] to titrate the optimal positive end-expiratory pressure (PEEP) in a swine model of acute respiratory distress syndrome (ARDS). Twelve swine models of ARDS were constructed. A lung recruitment maneuver was then conducted and the PEEP was set at 20 cm H 2 O. The PEEP was reduced by 2 cm H 2 O every 10 min until 0 cm H 2 O was reached, and VD/VT was measured after each decrement step. VD/VT was measured using single-breath analysis of CO 2 , and calculated from arterial CO 2 partial pressure (PaCO 2 ) and mixed expired CO 2 (PeCO 2 ) using the following formula: VD/VT = (PaCO 2 - PeCO 2 )/PaCO 2 . The optimal PEEP was identified by the lowest VD/VT method. Respiration and hemodynamic parameters were recorded during the periods of pre-injury and injury, and at 4 and 2 cm H 2 O below and above the optimal PEEP (Po). The optimal PEEP in this study was found to be 13.25±1.36 cm H 2 O. During the Po period, VD/VT decreased to a lower value (0.44±0.08) compared with that during the injury period (0.68±0.10) (P<0.05), while the intrapulmonary shunt fraction reached its lowest value. In addition, a significant change of dynamic tidal respiratory compliance and oxygenation index was induced by PEEP titration. These results indicate that minimal VD/VT can be used for PEEP titration in ARDS.

Effects of the Acrylic Polyol Structure and the Selectivity of the Employed Catalyst on the Performance of Two-Component Aqueous Polyurethane Coatings

PubMed Central

Cakic, Suzana; Lacnjevac, Caslav; Stamenkovic, Jakov; Ristic, Nikola; Takic, Ljiljana; Barac, Miroljub; Gligoric, Miladin

2007-01-01

Two kinds of aqueous acrylic polyols (single step and multi step synthesis type) have been investigated for their performance in the two-component aqueous polyurethane application, by using more selective catalysts. The aliphatic polyfunctional isocyanates based on hexamethylen diisocyanates have been employed as suitable hardeners. The complex of zirconium, commercially known as K-KAT®XC-6212, and manganese (III) complexes with mixed ligands based on the derivative of maleic acid have been used as catalysts in this study. Both of the aqueous polyols give good results, in terms of application and hardness, when elevated temperatures and more selective catalysts are applied. A more selective catalyst promotes the reaction between the isocyanate and polyol component. This increases the percentage of urethane bonds and the degree of hardness in the films formed from the two components of aqueous polyurethane lacquers. The polyol based on the single step synthesis route is favourable concerning potlife and hardness. The obtained results show that the performance of the two-component aqueous polyurethane coatings depends on the polymer structure of the polyols as well as on the selectivity of the employed catalyst.

Inactivation of virus in intravenous immunoglobulin G using solvent/detergent treatment and pasteurization.

PubMed

Aghaie, A; Pourfatollah, A A; Bathaie, S Z; Moazzeni, S M; Khorsand Mohammad Pour, H; Sharifi, Z

2008-01-01

The safety of plasma derived medicinal products, such as immunoglobulin, depends on viral inactivation steps that are incorporated into the production process. Several attempts have been made to validate the effectiveness of these inactivation methods against a range of physio-chemically diverse viruses. Treatment with solvent/detergent (S/D) and pasteurization (P) has been continuously used in our IgG production and these methods were analysed in this study as models of viral inactivation. Bovine Viral Diarrhoea Virus (BVDV), Herpes Simplex Virus (HSV) and Vesicular Stomatitis Virus (VSV) were employed as models of HCV, HBV and HIV respectively. Polio and Reo viruses also were used as stable viruses to chemical substances. The infectivity of a range of viruses before and after treatment with two methods of viral inactivation was measured by end point titration and their effectiveness expressed as Logarithmic Reduction Factors (LRF). Solvent/detergent treatment reduced the amount of enveloped viruses by 5-6 logs. The reduction factor was between 5-6 logs for all viruses used in the pasteurization process. A final log reduction factor was obtained as the sum of the two individual methods. Both inactivation methods have advantages and disadvantages with respect to their ability to inactivate viruses. Thus,combination of two robust virus inactivation steps, solvent/detergent and pasteurization, increases the safety margin of immunoglobulin preparations.

Free-Flow Zone Electrophoresis of Peptides and Proteins in PDMS Microchip for Narrow pI Range Sample Prefractionation Coupled with Mass Spectrometry

PubMed Central

Song, Yong-Ak; Chan, Michael; Celio, Chris; Tannenbaum, Steven R.; Wishnok, John S.; Han, Jongyoon

2010-01-01

In this paper, we are evaluating the strategy of sorting peptides / proteins based on the charge to mass without resorting to ampholytes and / or isoelectric focusing, using a single- and two-step free-flow zone electrophoresis. We developed a simple fabrication method to create a salt bridge for free-flow zone electrophoresis in PDMS chips by surface printing a hydrophobic layer on a glass substrate. Since the surface-printed hydrophobic layer prevents plasma bonding between the PDMS chip and the substrate, an electrical junction gap can be created for free-flow zone electrophoresis. With this device, we demonstrated a separation of positive and negative peptides and proteins at a given pH in standard buffer systems, and validated the sorting result with LC/MS. Furthermore, we coupled two sorting steps via off-chip titration, and isolated peptides within specific pI ranges from sample mixtures, where the pI range was simply set by the pH values of the buffer solutions. This free-flow zone electrophoresis sorting device, with its simplicity of fabrication, and a sorting resolution of 0.5 pH unit, can potentially be a high-throughput sample fractionation tool for targeted proteomics using LC/MS. PMID:20163146

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.

Graphene oxide for acid catalyzed-reactions: Effect of drying process

NASA Astrophysics Data System (ADS)

Gong, H. P.; Hua, W. M.; Yue, Y. H.; Gao, Z.

2017-03-01

Graphene oxides (GOs) were prepared by Hummers method through various drying processes, and characterized by XRD, SEM, FTIR, XPS and N2 adsorption. Their acidities were measured using potentiometric titration and acid-base titration. The catalytic properties were investigated in the alkylation of anisole with benzyl alcohol and transesterification of triacetin with methanol. GOs are active catalysts for both reaction, whose activity is greatly affected by their drying processes. Vacuum drying GO exhibits the best performance in transesterification while freezing drying GO is most active for alkylation. The excellent catalytic behavior comes from abundant surface acid sites as well as proper surface functional groups, which can be obtained by selecting appropriate drying process.

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.

A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting.

PubMed

Bruyère, Olivier; Cooper, Cyrus; Pelletier, Jean-Pierre; Maheu, Emmanuel; Rannou, François; Branco, Jaime; Luisa Brandi, Maria; Kanis, John A; Altman, Roy D; Hochberg, Marc C; Martel-Pelletier, Johanne; Reginster, Jean-Yves

2016-02-01

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) published a treatment algorithm for the management of knee osteoarthritis (OA) in 2014, which provides practical guidance for the prioritization of interventions. Further analysis of real-world data for OA provides additional evidence in support of pharmacological interventions, in terms of management of OA pain and function, avoidance of adverse events, disease-modifying effects and long-term outcomes, e.g., delay of total joint replacement surgery, and pharmacoeconomic factors such as reduction in healthcare resource utilization. This article provides an updated assessment of the literature for selected interventions in OA, focusing on real-life data, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA in primary care clinical practice, in support of the clinicians' individualized assessment of the patient. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) is recommended, for which high-quality evidence is provided only for the prescription formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti-inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs without the systemic safety concerns. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk:benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained-release tramadol, a weak opioid, affords sustained analgesia with improved tolerability. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

Selective catalytic two-step process for ethylene glycol from carbon monoxide

PubMed Central

Dong, Kaiwu; Elangovan, Saravanakumar; Sang, Rui; Spannenberg, Anke; Jackstell, Ralf; Junge, Kathrin; Li, Yuehui; Beller, Matthias

2016-01-01

Upgrading C1 chemicals (for example, CO, CO/H2, MeOH and CO2) with C–C bond formation is essential for the synthesis of bulk chemicals. In general, these industrially important processes (for example, Fischer Tropsch) proceed at drastic reaction conditions (>250 °C; high pressure) and suffer from low selectivity, which makes high capital investment necessary and requires additional purifications. Here, a different strategy for the preparation of ethylene glycol (EG) via initial oxidative coupling and subsequent reduction is presented. Separating coupling and reduction steps allows for a completely selective formation of EG (99%) from CO. This two-step catalytic procedure makes use of a Pd-catalysed oxycarbonylation of amines to oxamides at room temperature (RT) and subsequent Ru- or Fe-catalysed hydrogenation to EG. Notably, in the first step the required amines can be efficiently reused. The presented stepwise oxamide-mediated coupling provides the basis for a new strategy for selective upgrading of C1 chemicals. PMID:27377550

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

Kuhn, M., E-mail: kuhnm@mit.edu; Hashimoto, S.; Sato, K.

The oxygen nonstoichiometry of La{sub 0.6}Sr{sub 0.4}CoO{sub 3-{delta}} has been the topic of various reports in the literature, but has been exclusively measured at high oxygen partial pressures, pO{sub 2}, and/or elevated temperatures. For applications of La{sub 0.6}Sr{sub 0.4}CoO{sub 3-{delta}}, such as solid oxide fuel cell cathodes or oxygen permeation membranes, knowledge of the oxygen nonstoichiometry and thermo-chemical stability over a wide range of pO{sub 2} is crucial, as localized low pO{sub 2} could trigger failure of the material and device. By employing coulometric titration combined with thermogravimetry, the oxygen nonstoichiometry of La{sub 0.6}Sr{sub 0.4}CoO{sub 3-{delta}} was measured at highmore » and intermediate pO{sub 2} until the material decomposed (at log(pO{sub 2}/bar) Almost-Equal-To -4.5 at 1073 K). For a gradually reduced sample, an offset in oxygen content suggests that La{sub 0.6}Sr{sub 0.4}CoO{sub 3-{delta}} forms a 'super-reduced' solid solution before decomposing. When the sample underwent alternate reduction-oxidation, a hysteresis-like pO{sub 2} dependence of the oxygen content in the decomposition pO{sub 2} range was attributed to the reversible formation of ABO{sub 3} and A{sub 2}BO{sub 4} phases. Reduction enthalpy and entropy were determined for the single-phase region and confirmed interpolated values from the literature. - Graphical abstract: Oxygen nonstoichiometry (shown as 3-{delta}) of La{sub 0.6}Sr{sub 0.4}CoO{sub 3-{delta}} as a function of pO{sub 2} at 773-1173 K. The experimental data were obtained by thermogravimetric analysis (TG) and coulometric titration (measured either by a simple reduction (CT1) or a 'two-step-forward one-step-back' reduction-oxidation (CT2) procedure). D1 and D2 denote the decomposition pO{sub 2}. The solid lines are the fit to the thermogravimetry and CT1 data. The dashed lines represent the non-equilibrium region where the sample shows a super-reduced state. Highlights: Black-Right-Pointing-Pointer Oxygen nonstoichiometry of La{sub 0.6}Sr{sub 0.4}CoO{sub 3-{delta}} at intermediate temperatures and p(O2). Black-Right-Pointing-Pointer Experimental confirmation of previously interpolated reduction enthalpy. Black-Right-Pointing-Pointer Decomposition p(O2) assessed by coulometric titration. Black-Right-Pointing-Pointer Hysteresis-like p(O2) dependence of oxygen content at decomposition p(O2).« less

Determination of the total acidity in soft drinks using potentiometric sequential injection titration.

PubMed

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

2002-12-06

A potentiometric SI titration system for the determination of total acidity in soft drinks is proposed. The concept is based on the aspiration of the acid soft drink sample between two base zones into a holding coil with the volume of the first base zone twice to that of the second one and channelled by flow reversal through a reaction coil to a potentiometric sensor. A solution of 0.1 mol l(-1) sodium chloride is used as ionic strength adjustment buffer in the carrier stream. The system has been applied to the analysis of some South African soft drinks having a total acidity level of about 0.2-0.3% (w/v). The method has a sample frequency of 45 samples per h with a linear range of 0.1 and 0.6% (w/v). It is easy to use, fully computerised, and gives the results that are comparable to both automated batch titration and manual titration.

3-[(E)-(acridin-9‧-ylmethylidene)amino]-1-substituted thioureas and their biological activity

NASA Astrophysics Data System (ADS)

Bečka, Michal; Vilková, Mária; Salem, Othman; Kašpárková, Jana; Brabec, Viktor; Kožurková, Mária

2017-06-01

This paper describes the synthesis of a novel series of acridine thiosemicarbazones through a two-step reaction between various isothiocyanates and hydrazine followed by treatment with acridin-9-carbaldehyde. The properties of this series of seven new derivatives are studied using NMR and biochemical techniques, and the DNA-binding properties of the compounds are determined using spectrophotometric studies (UV-vis absorption, fluorescence, and circular/linear dichroism) and viscometry. The binding constants K are estimated as being in the range of 2.2 to 7.8 × 104 M- 1 and the percentage of hypochromism was found to be 22.11-49.75% (from UV-vis spectral titration). Electrophoretic experiments prove that the novel compounds demonstrate moderate inhibitory effects against Topo I activity at a concentration of 60 × 10- 6 M.

Psychotropic treatments in Prader-Willi syndrome: a critical review of published literature.

PubMed

Bonnot, O; Cohen, D; Thuilleaux, D; Consoli, A; Cabal, S; Tauber, M

2016-01-01

Prader-Willi syndrome (PWS) is a rare genetic syndrome. The phenotype includes moderate to intellectual disability, dysmorphia, obesity, and behavioral disturbances (e.g., hetero and self-injurious behaviors, hyperphagia, psychosis). Psychotropic medications are widely prescribed in PWS for symptomatic control. We conducted a systematic review of published literature to examine psychotropic medications used in PWS. MEDLINE was searched to identify articles published between January 1967 and December 2014 using key words related to pharmacological treatments and PWS. Articles with original data were included based on a standardized four-step selection process. The identification of studies led to 241 records. All selected articles were evaluated for case descriptions (PWS and behavioral signs) and treatment (type, titration, efficiency, and side effects). Overall, 102 patients were included in these studies. Treatment involved risperidone (three reports, n = 11 patients), fluoxetine (five/n = 6), naltrexone (two/n = 2), topiramate (two/n = 16), fluvoxamine (one/n = 1), mazindol (one/n = 2), N-acetyl cysteine (one/n = 35), rimonabant (one/n = 15), and fenfluramine (one/n = 15). We identified promising treatment effects with topiramate for self-injury and impulsive/aggressive behaviors, risperidone for psychotic symptoms associated with uniparental disomy (UPD), and N-acetyl cysteine for skin picking. The pharmacological approach of behavioral impairment in PWS has been poorly investigated to date. Further randomized controlled studies are warranted. Behavioral disturbances in Prader-Willi syndrome including aggressive reactions, skin picking, and hyperphagia might be very difficult to manage. Antipsychotic drugs are widely prescribed, but weight gain and increased appetite are their major side effects. Topiramate might be efficient for self-injury and impulsive/aggressive behaviors, N-acetyl cysteine is apromising treatment for skin picking and Antidepressants are indicated for OCD symptoms. Risperidone is indicated in case of psychotic symptoms mainly associated with uniparental disomy.

Kinetic titration with differential thermometric determination of the end-point.

PubMed

Sajó, I

1968-06-01

A method has been described for the determination of concentrations below 10(-4)M by applying catalytic reactions and using thermometric end-point determination. A reference solution, identical with the sample solution except for catalyst, is titrated with catalyst solution until the rates of reaction become the same, as shown by a null deflection on a galvanometer connected via bridge circuits to two opposed thermistors placed in the solutions.

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

Tang, Guoping; Luo, Wensui; Brooks, Scott C

We conducted batch and recirculating column titration tests with contaminated acidic sediments with controlled CO2 in the headspace, and extended the geochemical model by Gu et al. (2003, GCA) to better understand and quantify the reactions governing trace metal fate in the subsurface. The sediment titration curve showed slow pH increase due to strong buffering by Al precipitation and CO2 uptake. Assuming precipitation of basaluminite at low saturation index (SI=-4), and decreasing cation exchange selectivity coefficient (kNa\\Al=0.3), the predictions are close to the observed pH and Al; and the model explains 1) the observed Ca, Mg, and Mn concentration decreasemore » by cation exchange with sorbed Al, and 2) the decrease of U by surface complexation with Fe hydroxides at low pH, and precipitation as liebigite (Ca2UO2(CO3)3:10H2O) at pH>5.5. Without further adjustment geochemical parameters, the model describes reasonably well previous sediment and column titration tests without CO2 in the headspace, as well as the new large column test. The apparent inhibition of U and Ni decrease in the large column can be explained by formation of aqueous carbonate complexes and/or competition with carbonate for surface sites. These results indicated that ignoring labile solid phase Al would underestimate base requirement in titration of acidic aquifers.« less

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)

A two-step leaching method designed based on chemical fraction distribution of the heavy metals for selective leaching of Cd, Zn, Cu, and Pb from metallurgical sludge.

PubMed

Wang, Fen; Yu, Junxia; Xiong, Wanli; Xu, Yuanlai; Chi, Ru-An

2018-01-01

For selective leaching and highly effective recovery of heavy metals from a metallurgical sludge, a two-step leaching method was designed based on the distribution analysis of the chemical fractions of the loaded heavy metal. Hydrochloric acid (HCl) was used as a leaching agent in the first step to leach the relatively labile heavy metals and then ethylenediamine tetraacetic acid (EDTA) was applied to leach the residual metals according to their different fractional distribution. Using the two-step leaching method, 82.89% of Cd, 55.73% of Zn, 10.85% of Cu, and 0.25% of Pb were leached in the first step by 0.7 M HCl at a contact time of 240 min, and the leaching efficiencies for Cd, Zn, Cu, and Pb were elevated up to 99.76, 91.41, 71.85, and 94.06%, by subsequent treatment with 0.2 M EDTA at 480 min, respectively. Furthermore, HCl leaching induced fractional redistribution, which might increase the mobility of the remaining metals and then facilitate the following metal removal by EDTA. The facilitation was further confirmed by the comparison to the one-step leaching method with single HCl or single EDTA, respectively. These results suggested that the designed two-step leaching method by HCl and EDTA could be used for selective leaching and effective recovery of heavy metals from the metallurgical sludge or heavy metal-contaminated solid media.

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)

Application of a taste evaluation system to the monitoring of Kimchi fermentation.

PubMed

Kim, Namsoo; Park, Kyung-Rim; Park, In-Seon; Cho, Yong-Jin; Bae, Young Min

2005-05-15

As an objective method, taste evaluation with an instrument is able to supplement the subjective sensory evaluation and to be applied to the optimization of food processing. Kimchi, a Korean traditional pickle fermented with lactic acid bacteria, is expanding its consumption worldwide. The fermentation control of it has been routinely done by measuring titratable acidity and pH. In this study, an eight-channel taste evaluation system was prepared, followed by an application to the monitoring of Kimchi fermentation. Eight polymer membranes which individually responded to cationic or anionic substances were prepared by mixing electroactive materials such as tri-n-octylmethylammonium chloride, bis(2-ethylhexyl)sebacate as the plasticizer and polyvinyl chloride in the ratio of 1:66:33. Each membrane prepared was separately installed onto the sensitive area of an ion-selective electrode to produce the respective taste sensor. The eight-channel sensor array and a double junction reference electrode were connected to a 16-channel high input impedance amplifier. The amplified sensor signals were stored to a personal computer via a multi-channel A/D converter. Two sensor groups composed of the cation-selective and anion-selective polymer membrane electrodes showed characteristic concentration-dependency to various artificial taste substances. As a whole, the response potentials of the sensor array increased during the fermentation period at 4, 10 and 25 degrees C. Even the response potentials of the anion-selective taste sensors slightly increased possibly due to the protonation of anions by liberated H+ ions, thereby leading to a decrease in the anion concentration. When the signal data were interpreted by principal component analysis (PCA), the first PC at 4 degrees C explained most of the total data variance. A close correlation was found between the values of titratable acidity and the first PC, which indicated a possible applicability of the multi-channel taste sensor of this study to the process monitoring of various pickle.

Coulometric thermometric titration of halides in molten calcium nitrate tetrahydrate.

PubMed

Zsigrai, I J; Bartusz, D B

1983-01-01

A method for coulometric thermometric precipitation titrations of chloride, bromide and iodide in molten calcium nitrate tetrahydrate at 55 degrees with coulometrically generated silver ions has been developed. The change in temperature during the titration is followed with the aid of a thermistor bridge coupled to a recorder. To minimize the temperature effect of the passage of current through the melt, two thermistors are connected in opposition in the bridge, with one in the anodic and the other in the cathodic cell compartment. Amounts of 62-80 mumole of halide have been determined with relative error below 0.4% and relative standard deviation less than 2.7%. The relative error in determination of 40 mumole of iodide was + 2%.

Coulometrische titration von hypochloriten und chloraten.

PubMed

Gründler, P; Holzapfel, H

1970-03-01

Hypochlorite was determined by direct coulometric titration with iron(II) in an acetate buffered solution. Chlorate was titrated with titanium(III) in 2M hydrochloric acid. Amperometric indication with one and two electrodes, respectively, was used. Mixtures of hypochlorites and chlorates, e.g., in industrial electrolytes, may be analysed. On a déterminé l'hypochlorite par titrage coulométrique direct avec le fer(II) dans une solution tamponnée à l'acétate. On a titré le chlorate avec le titane(III) en acide chlorhydrique 2M. On a utilisé l'indication ampérométrique une et deux électrodes respectivement. On peut analyser des mélanges d'hypochlorites et de chlorates, par exemple dans des électrolytes industriels.

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.

Two-year Randomized Clinical Trial of Self-etching Adhesives and Selective Enamel Etching.

PubMed

Pena, C E; Rodrigues, J A; Ely, C; Giannini, M; Reis, A F

2016-01-01

The aim of this randomized, controlled prospective clinical trial was to evaluate the clinical effectiveness of restoring noncarious cervical lesions with two self-etching adhesive systems applied with or without selective enamel etching. A one-step self-etching adhesive (Xeno V(+)) and a two-step self-etching system (Clearfil SE Bond) were used. The effectiveness of phosphoric acid selective etching of enamel margins was also evaluated. Fifty-six cavities were restored with each adhesive system and divided into two subgroups (n=28; etch and non-etch). All 112 cavities were restored with the nanohybrid composite Esthet.X HD. The clinical effectiveness of restorations was recorded in terms of retention, marginal integrity, marginal staining, caries recurrence, and postoperative sensitivity after 3, 6, 12, 18, and 24 months (modified United States Public Health Service). The Friedman test detected significant differences only after 18 months for marginal staining in the groups Clearfil SE non-etch (p=0.009) and Xeno V(+) etch (p=0.004). One restoration was lost during the trial (Xeno V(+) etch; p>0.05). Although an increase in marginal staining was recorded for groups Clearfil SE non-etch and Xeno V(+) etch, the clinical effectiveness of restorations was considered acceptable for the single-step and two-step self-etching systems with or without selective enamel etching in this 24-month clinical trial.

Validation of spot-testing kits to determine iodine content in salt.

PubMed Central

Pandav, C. S.; Arora, N. K.; Krishnan, A.; Sankar, R.; Pandav, S.; Karmarkar, M. G.

2000-01-01

Iodine deficiency disorders are a major public health problem, and salt iodization is the most widely practised intervention for their elimination. For the intervention to be successful and sustainable, it is vital to monitor the iodine content of salt regularly. Iodometric titration, the traditional method for measuring iodine content, has problems related to accessibility and cost. The newer spot-testing kits are inexpensive, require minimal training, and provide immediate results. Using data from surveys to assess the availability of iodized salt in two states in India, Madhya Pradesh and the National Capital Territory of Delhi, we tested the suitability of such a kit in field situations. Salt samples from Delhi were collected from 30 schools, chosen using the Expanded Programme on Immunization (EPI) cluster sampling technique. A single observer made the measurement for iodine content using the kit. Salt samples from Madhya Pradesh were from 30 rural and 30 urban clusters, identified by using census data and the EPI cluster sampling technique. In each cluster, salt samples were collected from 10 randomly selected households and all retailers. The 15 investigators performing the survey estimated the iodine content of salt samples in the field using the kit. All the samples were brought to the central laboratory in Delhi, where iodine content was estimated using iodometric titration as a reference method. The agreement between the kit and titration values decreased as the number of observers increased. Although sensitivity was not much affected by the increase in the number of observers (93.3% for a single observer and 93.9% for multiple observers), specificity decreased sharply (90.4% for a single observer and 40.4% for multiple observers). Due to the low specificity and resulting high numbers of false-positives for the kit when used by multiple observers ("real-life situations"), kits were likely to consistently overestimate the availability of iodized salt. This overestimation could result in complacency. Therefore, we conclude that until a valid alternative is available, the titration method should be used for monitoring the iodine content of salt at all levels, from producer to consumer, to ensure effectiveness of the programme. PMID:10994281

New analytical methodology for analysing S(IV) species at low pH solutions by one stage titration method (bichromatometry) with a clear colour change. Could potentially replace the state-of-art-method iodometry at low pH analysis due higher accuracy

PubMed Central

Galfi, Istvan; Virtanen, Jorma; Gasik, Michael M.

2017-01-01

A new, faster and more reliable analytical methodology for S(IV) species analysis at low pH solutions by bichromatometry is proposed. For decades the state of the art methodology has been iodometry that is still well justified method for neutral solutions, thus at low pH media possess various side reactions increasing inaccuracy. In contrast, the new methodology has no side reactions at low pH media, requires only one titration step and provides a clear color change if S(IV) species are present in the solution. The method is validated using model solutions with known concentrations and applied to analyses of gaseous SO2 from purged solution in low pH media samples. The results indicate that bichromatometry can accurately analyze SO2 from liquid samples having pH even below 0 relevant to metallurgical industrial processes. PMID:29145479

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.

Comparison of ozone determinations by ultraviolet photometry and gas-phase titration

NASA Technical Reports Server (NTRS)

Demore, W. B.; Patapoff, M.

1976-01-01

A comparison of ozone determinations based on ultraviolet absorption photometry and gas-phase titration (GPT) shows good agreement between the two methods. Together with other results, these findings indicate that three candidate reference methods for ozone, UV photometry, IR photometry, and GPT are in substantial agreement. However, the GPT method is not recommended for routine use by air pollution agencies for calibration of ozone monitors because of susceptibility to experimental error.

Understanding water content data in cottons equilibrated to moisture equilibrium

USDA-ARS?s Scientific Manuscript database

The accurate measurement of moisture in cottons conditioned to moisture equilibrium and understanding the data are prerequisites to the development of applications of the data. In this study, moisture is measured by Karl Fischer Titration, which is highly selective for water in cotton; the results ...

The Analysis of Seawater: A Laboratory-Centered Learning Project in General Chemistry.

ERIC Educational Resources Information Center

Selco, Jodye I.; Roberts, Julian L., Jr.; Wacks, Daniel B.

2003-01-01

Describes a sea-water analysis project that introduces qualitative and quantitative analysis methods and laboratory methods such as gravimetric analysis, potentiometric titration, ion-selective electrodes, and the use of calibration curves. Uses a problem-based cooperative teaching approach. (Contains 24 references.) (YDS)

Conformational selection in a protein-protein interaction revealed by dynamic pathway analysis

DOE PAGES

Chakrabarti, Kalyan S.; Agafonov, Roman V.; Pontiggia, Francesco; ...

2015-12-24

Molecular recognition plays a central role in biology, and protein dynamics has been acknowledged to be important in this process. However, it is highly debated whether conformational changes happen before ligand binding to produce a binding-competent state (conformational selection) or are caused in response to ligand binding (induced fit). Proposals for both mechanisms in protein/protein recognition have been primarily based on structural arguments. However, the distinction between them is a question of the probabilities of going via these two opposing pathways. Here we present a direct demonstration of exclusive conformational selection in protein/protein recognition by measuring the flux for rhodopsinmore » kinase binding to its regulator recoverin, an important molecular recognition in the vision system. Using NMR spectroscopy, stopped-flow kinetics and isothermal titration calorimetry we show that recoverin populates a minor conformation in solution that exposes a hydrophobic binding pocket responsible for binding rhodopsin kinase. Lastly, protein dynamics in free recoverin limits the overall rate of binding.« less

Conformational selection in a protein-protein interaction revealed by dynamic pathway analysis

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

Chakrabarti, Kalyan S.; Agafonov, Roman V.; Pontiggia, Francesco

Molecular recognition plays a central role in biology, and protein dynamics has been acknowledged to be important in this process. However, it is highly debated whether conformational changes happen before ligand binding to produce a binding-competent state (conformational selection) or are caused in response to ligand binding (induced fit). Proposals for both mechanisms in protein/protein recognition have been primarily based on structural arguments. However, the distinction between them is a question of the probabilities of going via these two opposing pathways. Here we present a direct demonstration of exclusive conformational selection in protein/protein recognition by measuring the flux for rhodopsinmore » kinase binding to its regulator recoverin, an important molecular recognition in the vision system. Using NMR spectroscopy, stopped-flow kinetics and isothermal titration calorimetry we show that recoverin populates a minor conformation in solution that exposes a hydrophobic binding pocket responsible for binding rhodopsin kinase. Lastly, protein dynamics in free recoverin limits the overall rate of binding.« less

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.

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.

Contribution of Glucose Transport to the Control of the Glycolytic Flux in Trypanosoma brucei

NASA Astrophysics Data System (ADS)

Bakker, Barbara M.; Walsh, Michael C.; Ter Kuile, Benno H.; Mensonides, Femke I. C.; Michels, Paul A. M.; Opperdoes, Fred R.; Westerhoff, Hans V.

1999-08-01

The rate of glucose transport across the plasma membrane of the bloodstream form of Trypanosoma brucei was modulated by titration of the hexose transporter with the inhibitor phloretin, and the effect on the glycolytic flux was measured. A rapid glucose uptake assay was developed to measure the transport activity independently of the glycolytic flux. Phloretin proved a competitive inhibitor. When the effect of the intracellular glucose concentration on the inhibition was taken into account, the flux control coefficient of the glucose transporter was between 0.3 and 0.5 at 5 mM glucose. Because the flux control coefficients of all steps in a metabolic pathway sum to 1, this result proves that glucose transport is not the rate-limiting step of trypanosome glycolysis. Under physiological conditions, transport shares the control with other steps. At glucose concentrations much lower than physiological, the glucose carrier assumed all control, in close agreement with model predictions.

(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

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...

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)

A short 2 week dose titration regimen reduces the severity of flu-like symptoms with initial interferon gamma-1b treatment.

PubMed

Devane, John G; Martin, Mary L; Matson, Mark A

2014-06-01

Flu-like symptoms (FLS) are commonly experienced by patients receiving interferon gamma-1b which may cause discontinuation or disruption of dosing during initial therapy or on re-initiation following a break in therapy. In contrast to Type I interferons, the impact of dose-titration on FLS has not been reported and is not a practice described or included in the approved prescribing information for interferon gamma-1b.The objective of this study was to assess the effect of a 2 week titration regimen on the severity of FLS during the initial 3 weeks of therapy with three times weekly subcutaneous injections of interferon gamma-1b. Healthy men and women were randomized into a double-blind, two-period, crossover study. Each study period was 3 weeks in duration and there was a minimum 15 day washout between treatment periods. Two treatment regimens were compared: No Titration dosing (full 50 mcg/m(2) subcutaneously [s.c.] three times weekly for 3 weeks) and Titration (15 mcg/m(2) s.c. three times weekly during week 1, 30 mcg/m(2) s.c. three times weekly during week 2 followed by the full dose of 50 mcg/m(2) s.c. three times weekly during week 3). Subjects remained in the clinic for at least 12 hours following each injection. FLS was based on a composite score for fever, chills, tiredness and muscle aches assessed at baseline and 4, 8 and 12 hours following each injection. Acetaminophen was allowed at the discretion of the PI. The primary endpoint was the change from baseline in FLS severity at 8 hours averaged over the 3 weeks of treatment. Additional endpoints included FLS at 4 and 12 hours, individual flu-like symptoms, rates of discontinuation, incidence of FLS and acetaminophen use. NCT 01929382. Of the 40 subjects randomized, there were 15 (37.5%) discontinuations. Titration resulted in a significant reduction in FLS severity at 8 hours (p = 0.023) averaged over the 3 week treatment period. The difference in 3 week FLS severity reflects differences during week 1 treatment, indicating an early peak in FLS severity during the No Titration treatment and subsequent development of tolerance. In contrast, titration results in near baseline severity scores throughout the treatment period. Similar trends were seen for 4 and 12 hour FLS severity scores. Of the individual FLS, difference in fever severity was most marked. Safety profiles for both regimens were consistent with the approved prescribing information for interferon gamma-1b. Study limitations included the use of healthy subjects rather than disease subjects, the lack of a validated assessment tool for evaluating FLS and the relatively high discontinuation rate. A short 2 week, dose-titration regimen reduces FLS severity following interferon gamma-1b treatment initiation in normal subjects.

Investigation of the use of thermometric titrimetry for the determination of acidic substances in wine.

PubMed

Godinho, O E; Coelho, J A; Chagas, A P; Aleixo, L M

1984-03-01

The use of thermometric titrimetry in the determination of acidic substances in red wine is described. The titration curve obtained in the thermometric titration of red wine with strong base presents two inflections. The stoichiometry corresponding to the first inflection presents good agreement with the so-called "total acidity" of wine, and is proposed for its determination. The second inflection is related to the content of phenolic substances in red wine.

Best Technical Approach for the Petroleum Quality Analysis (PQA) System

DTIC Science & Technology

1994-08-01

two test methods for determination of water content in a fuel. The Karl Fischer titration method (ASTM D 1744) measures for total water, both...difficult to automate. ASTM D 664, "Standard Test Method for Acid Number of Petroleum Products by Potentiometric Titration," is simple to automate...release. distribution unlimnied 13. ABSTRACT (Maximum 2C3 words) Recent U.S. militar-y operations have identified a need for improved methods of fuel and

The effect of packaging methods (paper, active paper, and edible coating) on the characteristic of papaya MJ9 in ambient temperature storage

NASA Astrophysics Data System (ADS)

Suwanti, D.; Utami, R.; Kawiji; Praseptiangga, D.; Khasanah, L. U.

2018-01-01

Papaya is one of the export commodities that contain high vitamin C but having short shelf-life. One method that use to extend the shelf-life and maintain the quality of papaya is packaging. The aim of this study was to investigate the effect of the packaging methods (paper, active paper and edible coating) on the characteristics of papaya MJ9 (weight loss, firmness, total soluble solid (TSS), Total Titratable Acid (TTA), pH, vitamin C and total mold and yeast). The packaging methods were control (F1), wrapping paper (F2), wrapping active paper (F3), combination of edible coating and wrapping paper (F4), and combination of edible coating and wrapping active paper (F5). The result showed that paper packaging, edible coating and active paper packaging significantly affected the weight loss, firmness, total soluble solid, total titratable acids, pH, vitamin C, and total mold and yeast of papaya. The weight loss, total soluble solid and pH of packaged papaya was lower than that of control sample, however, the value of firmness and total titratable acid was higher than that of the control sample. Packaging can inhibit the increase of weight loss, total soluble solids and pH, and the decrease of firmness, total titratable acid, vitamin C and total mold and yeast. Based on the papaya characteristics, the selected packaging method was the combination of edible coating and wrapping active paper.

Acridine-based fluorescence chemosensors for selective sensing of Fe3+ and Ni2+ ions

NASA Astrophysics Data System (ADS)

Wang, Chaoyu; Fu, Jiaxin; Yao, Kun; Xue, Kun; Xu, Kuoxi; Pang, Xiaobin

2018-06-01

Two novel acridine-based fluorescence chemosensors (L1 and L2) were prepared and their metal ions sensing properties were investigated. L1 (L2) exhibited an excellent selective fluorescence response toward Fe3+ (Ni2+) and the stoichiometry ratio of L1-Fe3+ and L2-Ni2+ were 1:1. The detection limits of L1 and L2 were calculated by the fluorescence titration to be 4.13 μM and 1.52 μM, respectively, which were below the maximum permissive level of Fe3+ and Ni2+ ions in drinking water set by the EPA. The possible mechanism of the fluorescence detection of Fe3+ and Ni2+ had been proposed according to the analysis of Job's plot, IR spectra and ESI-MS. The determination of Fe3+ and Ni2+ ions in living cells had been applied successfully.

Effect of mass concentration of composite phase change material CA-DE on HCFC-141b hydrate induction time and system stability

NASA Astrophysics Data System (ADS)

Li, Juan; Sun, Zhigao; Liu, Chenggang; Zhu, Minggui

2018-03-01

HCFC-141b hydrate is a new type of environment-friendly cold storage medium which may be adopted to balance energy supply and demand, achieve peak load shifting and energy saving, wherein the hydrate induction time and system stability are key factors to promote and realize its application in industrial practice. Based on step cooling curve measurement, two kinds of aliphatic hydrocarbon organics, n-capric acid (CA) and lauryl alcohol (DE), were selected to form composite phase change material and to promote the generation of HCFC-141b hydrate. Five kinds of CA-DE mass concentration were chosen to compare the induction time and hydration system stability. In order to accelerate temperature reduction rate, the metal Cu with high heat conductivity performance was adopted to conduct out the heat generated during phase change. Instability index was introduced to appraise system stability. Experimental results show that phase change temperature and sub-cooling degree of CA-DE is 11.1°C and 3.0°C respectively, which means it is a preferable medium for HCFC-141b hydrate formation. For the experimental hydration systems, segmented emulsification is achieved by special titration manner to avoid rapid layering under static condition. Induction time can achieve up to 23.3min with the densest HCFC-141b hydrate and the lowest instability index, wherein CA-DE mass concentration is 3%.

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.

Amination of activated carbon for enhancing phenol adsorption: Effect of nitrogen-containing functional groups

NASA Astrophysics Data System (ADS)

Yang, Guo; Chen, Honglin; Qin, Hangdao; Feng, Yujun

2014-02-01

To study the contribution of different nitrogen-containing functional groups to enhancement of phenol adsorption, the aminated activated carbons (AC) were characterized by N2 adsorption/desorption, XPS, Boehm titration, and pH drift method and tested for adsorption behaviors of phenol. Adsorption isotherm fitting revealed that the Langmuir model was preferred for the aminated ACs. The adsorption capacity per unit surface area (qm/SSABET) was linearly correlated with the amount of pyridinic and pyrrolic N, which suggested that these two functional groups played a critical role in phenol adsorption. The enhancement of adsorption capacity was attributed to the strengthened π-π dispersion between phenol and basal plane of AC by pyridinic, pyrrolic N. The adsorption kinetics was found to follow the pseudo-second-order kinetic model, and intraparticle diffusion was one of the rate-controlling steps in the adsorption process.

Antibiotic Combinations That Enable One-Step, Targeted Mutagenesis of Chromosomal Genes.

PubMed

Lee, Wonsik; Do, Truc; Zhang, Ge; Kahne, Daniel; Meredith, Timothy C; Walker, Suzanne

2018-06-08

Targeted modification of bacterial chromosomes is necessary to understand new drug targets, investigate virulence factors, elucidate cell physiology, and validate results of -omics-based approaches. For some bacteria, reverse genetics remains a major bottleneck to progress in research. Here, we describe a compound-centric strategy that combines new negative selection markers with known positive selection markers to achieve simple, efficient one-step genome engineering of bacterial chromosomes. The method was inspired by the observation that certain nonessential metabolic pathways contain essential late steps, suggesting that antibiotics targeting a late step can be used to select for the absence of genes that control flux into the pathway. Guided by this hypothesis, we have identified antibiotic/counterselectable markers to accelerate reverse engineering of two increasingly antibiotic-resistant pathogens, Staphylococcus aureus and Acinetobacter baumannii. For S. aureus, we used wall teichoic acid biosynthesis inhibitors to select for the absence of tarO and for A. baumannii, we used colistin to select for the absence of lpxC. We have obtained desired gene deletions, gene fusions, and promoter swaps in a single plating step with perfect efficiency. Our method can also be adapted to generate markerless deletions of genes using FLP recombinase. The tools described here will accelerate research on two important pathogens, and the concept we outline can be readily adapted to any organism for which a suitable target pathway can be identified.

A Mixed Approach to Similarity Metric Selection in Affinity Propagation-Based WiFi Fingerprinting Indoor Positioning.

PubMed

Caso, Giuseppe; de Nardis, Luca; di Benedetto, Maria-Gabriella

2015-10-30

The weighted k-nearest neighbors (WkNN) algorithm is by far the most popular choice in the design of fingerprinting indoor positioning systems based on WiFi received signal strength (RSS). WkNN estimates the position of a target device by selecting k reference points (RPs) based on the similarity of their fingerprints with the measured RSS values. The position of the target device is then obtained as a weighted sum of the positions of the k RPs. Two-step WkNN positioning algorithms were recently proposed, in which RPs are divided into clusters using the affinity propagation clustering algorithm, and one representative for each cluster is selected. Only cluster representatives are then considered during the position estimation, leading to a significant computational complexity reduction compared to traditional, flat WkNN. Flat and two-step WkNN share the issue of properly selecting the similarity metric so as to guarantee good positioning accuracy: in two-step WkNN, in particular, the metric impacts three different steps in the position estimation, that is cluster formation, cluster selection and RP selection and weighting. So far, however, the only similarity metric considered in the literature was the one proposed in the original formulation of the affinity propagation algorithm. This paper fills this gap by comparing different metrics and, based on this comparison, proposes a novel mixed approach in which different metrics are adopted in the different steps of the position estimation procedure. The analysis is supported by an extensive experimental campaign carried out in a multi-floor 3D indoor positioning testbed. The impact of similarity metrics and their combinations on the structure and size of the resulting clusters, 3D positioning accuracy and computational complexity are investigated. Results show that the adoption of metrics different from the one proposed in the original affinity propagation algorithm and, in particular, the combination of different metrics can significantly improve the positioning accuracy while preserving the efficiency in computational complexity typical of two-step algorithms.

A Mixed Approach to Similarity Metric Selection in Affinity Propagation-Based WiFi Fingerprinting Indoor Positioning

PubMed Central

Caso, Giuseppe; de Nardis, Luca; di Benedetto, Maria-Gabriella

2015-01-01

The weighted k-nearest neighbors (WkNN) algorithm is by far the most popular choice in the design of fingerprinting indoor positioning systems based on WiFi received signal strength (RSS). WkNN estimates the position of a target device by selecting k reference points (RPs) based on the similarity of their fingerprints with the measured RSS values. The position of the target device is then obtained as a weighted sum of the positions of the k RPs. Two-step WkNN positioning algorithms were recently proposed, in which RPs are divided into clusters using the affinity propagation clustering algorithm, and one representative for each cluster is selected. Only cluster representatives are then considered during the position estimation, leading to a significant computational complexity reduction compared to traditional, flat WkNN. Flat and two-step WkNN share the issue of properly selecting the similarity metric so as to guarantee good positioning accuracy: in two-step WkNN, in particular, the metric impacts three different steps in the position estimation, that is cluster formation, cluster selection and RP selection and weighting. So far, however, the only similarity metric considered in the literature was the one proposed in the original formulation of the affinity propagation algorithm. This paper fills this gap by comparing different metrics and, based on this comparison, proposes a novel mixed approach in which different metrics are adopted in the different steps of the position estimation procedure. The analysis is supported by an extensive experimental campaign carried out in a multi-floor 3D indoor positioning testbed. The impact of similarity metrics and their combinations on the structure and size of the resulting clusters, 3D positioning accuracy and computational complexity are investigated. Results show that the adoption of metrics different from the one proposed in the original affinity propagation algorithm and, in particular, the combination of different metrics can significantly improve the positioning accuracy while preserving the efficiency in computational complexity typical of two-step algorithms. PMID:26528984

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.

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.

Preliminary findings on the correlation of saliva pH, buffering capacity, flow rate and consistency in relation to waterpipe tobacco smoking.

PubMed

Khemiss, Mehdi; Ben Khelifa, Mohamed; Ben Saad, Helmi

2017-12-01

The aim of the present comparative study was to compare some salivary characteristics between exclusive waterpipe smokers (EWPS) and non-smokers. 72 males (36 EWPS) were recruited. The volume of stimulated saliva was determined and divided by the duration of saliva collection. The pH was measured directly using a pH meter. The buffering capacity was determined using a quantitative method which involved the addition of 10 µl HCl. Up to a total of 160 µL was titrated up to obtain a pH titration curve. At 50 µL of titrated HCl, buffering capacity was ranked into three categories: high, medium and low. EWPS and non-smoker groups had similar flow rates (1.81 ± 0.79 and 1.78 ± 1.14 mL min-1) and similar baseline pH (6.60 ± 0.37 and 6.76 ± 0.39). Statistically significant differences in the two groups' pH were observed from 30 to 160 µL of titrated up HCl. At 50 µL of titrated up HCl, the EWPS group compared to the non-smoker group had a significantly higher pH (4.79 ± 0.72 vs. 5.32 ± 0.79). To conclude, waterpipe tobacco smoking alters the buffering capacity but does not alter either salivary flow rates or the baseline pH and consistency.

Simulation-Based Evaluation of Dose-Titration Algorithms for Rapid-Acting Insulin in Subjects with Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antihyperglycemic Medications.

PubMed

Ma, Xiaosu; Chien, Jenny Y; Johnson, Jennal; Malone, James; Sinha, Vikram

2017-08-01

The purpose of this prospective, model-based simulation approach was to evaluate the impact of various rapid-acting mealtime insulin dose-titration algorithms on glycemic control (hemoglobin A1c [HbA1c]). Seven stepwise, glucose-driven insulin dose-titration algorithms were evaluated with a model-based simulation approach by using insulin lispro. Pre-meal blood glucose readings were used to adjust insulin lispro doses. Two control dosing algorithms were included for comparison: no insulin lispro (basal insulin+metformin only) or insulin lispro with fixed doses without titration. Of the seven dosing algorithms assessed, daily adjustment of insulin lispro dose, when glucose targets were met at pre-breakfast, pre-lunch, and pre-dinner, sequentially, demonstrated greater HbA1c reduction at 24 weeks, compared with the other dosing algorithms. Hypoglycemic rates were comparable among the dosing algorithms except for higher rates with the insulin lispro fixed-dose scenario (no titration), as expected. The inferior HbA1c response for the "basal plus metformin only" arm supports the additional glycemic benefit with prandial insulin lispro. Our model-based simulations support a simplified dosing algorithm that does not include carbohydrate counting, but that includes glucose targets for daily dose adjustment to maintain glycemic control with a low risk of hypoglycemia.

Surface acid-base behaviors of Chinese loess.

PubMed

Chu, Zhaosheng; Liu, Wenxin; Tang, Hongxiao; Qian, Tianwei; Li, Shushen; Li, Zhentang; Wu, Guibin

2002-08-15

Acid-base titration was applied to investigate the surface acid-base properties of a Chinese loess sample at different ionic strengths. The acidimetric supernatant was regarded as the system blank of titration to correct the influence of particle dissolution on the estimation of proton consumption. The titration behavior of the system blank could be described by the hydrolysis of Al3+ and Si(OH)4 in aqueous solution as well as the production of hydroxyaluminosilicates. The formation of Al-Si species on homogeneous surface sites by hydrous aluminum and silicic acid, released from solid substrate during the acidic titration, was considered in the model description of the back-titration procedure. A surface reaction model was suggested as follows: >SOH<-->SO(-)+H+, pK(a)(int)=3.48-3.98;>SOH+Al(3+)+H4SiO4<-->SOAl(OSi(OH)3(+)+2H+, pK(SC)=3.48-4.04. Two simple surface complexation models accounted for the interfacial structure, i.e., the constant capacitance model (CCM) and the diffuse layer model (DLM), and gave a satisfactory description of the experimental data. Considering the effect of ionic strength on the electrostatic profile at the solid-aqueous interface, the DLM was appropriate at the low concentrations (0.01 and 0.005 mol/L) of background electrolyte (NaNO3 in this study), while the CCM was preferable in the case of high ionic strength (0.1 mol/L).

Comparison of the influence of polyaspartic acid and polylysine functional groups on the adsorption at the Cr2O3-Aqueous polymer solution interface

NASA Astrophysics Data System (ADS)

Ostolska, Iwona; Wiśniewska, Małgorzata

2014-08-01

Polyamino acids are a group of synthesized polymers obtained by polymerization of a given kind of amino acid monomer. Because of high biodegradability of this class of polymers, they can be used as flocculation or stabilization agents in the environmental aspects. Therefore determination of their influence on the stability of the aqueous suspension of metal oxides is important. An influence of different functional groups of polyamino acids, their molecular weight and concentration on the adsorption at the chromium (III) oxide (Cr2O3)-aqueous solution interface was determined. Experiments were carried out for four values of solution pH varying from 3 to 10 (3, 4, 7.6 and 10, respectively). Two polymers were used: anionic polyaspartic acid (ASP) of 6800 and 27,000 as well as polylysine (LYS) of 4900 and 33,000 molecular weights. Changes of surface charge density of colloidal Cr2O3 in the presence and in the absence of macromolecular substances were determined using potentiometric titration. In these studies the influence of the concentration and molecular weight of the ionic polymers on the pHpzc value was determined. Additionally, due to the lack of appropriate literature data, potentiometric titration of the selected polymers was performed to determine pKa values.

A comparison of sennosides-based bowel protocols with and without docusate in hospitalized patients with cancer.

PubMed

Hawley, Philippa Helen; Byeon, Jai Jun

2008-05-01

Constipation is a common and distressing condition in patients with cancer, especially those taking opioid analgesics. Many institutions prevent and treat constipation with titrated laxatives, which is known as a bowel protocol. An effective and well-tolerated bowel protocol is a very important component of cancer care, and there is little evidence on which to base selection of the most appropriate agents. This study compares a protocol of the stimulant laxative sennosides alone with a protocol of sennosides plus the stool softener docusate, in hospitalized patients at an oncology center. The docusate-containing protocol had an initial docusate-only step for patients not taking opioids, and four to six 100-mg capsules of docusate sodium in addition to the sennosides for the rest of the protocol. Thirty patients received the sennosides-only (S) protocol and 30 the sennosides plus docusate (DS) protocol. The efficacy and adverse effects of the protocols were monitored for 5-12 days. The two protocols were used sequentially, creating two cohorts, one on each protocol. Eighty percent of patients were taking oral opioids and 72% were admitted for symptom control/supportive care. Over a total of 488 days of observation it was found that the S protocol produced more bowel movements than the DS protocol, and in the symptom control/supportive care patients this difference was statistically significant (p < 0.05). In the S group admitted for symptom control/supportive care 62.5% had a bowel movement more than 50% of days, as compared with 32% in those receiving the DS protocol. Fifty-seven percent of the DS group required additional interventions (lactulose, suppositories or enemas) compared to 40% in the S group. Cramps were reported equally by 3 (10%) patients in each group. Eight patients (27%) experienced diarrhea in the S group compared to 4 (13%) in the DS group. The addition of the initial docusate-only step and adding docusate 400-600 mg/d to the sennosides did not reduce bowel cramps, and was less effective in inducing laxation than the sennosides-only protocol. Further research into the appropriate use of docusate and into the details of bowel protocol design are required.

Titration of Serum Lipoproteins with Lipoprotein Precipitants.

DTIC Science & Technology

1981-12-01

Lipid Res 11:583 (1970). 6. Grove, T. H. Effect of reagent pH on determination of high-density lipo- protein cholesterol by precipitation with sodium ...of choles- terol in the supernate plateaued at 43 mg/dl after the beta and prebeta lipo- proteins had been precipitated . The intensities of the two...AD-A113 370 SCHOOL OF AEROSPACE MEDICINE BROOKS AFS TX F/S 6/1 TITRATION OF SERU’LIPOPROTEINS WITH LIPOPROTEIN PRECIPITANTS .(Ul DEC 81 0 A CLARK. J A

Investigating calcite growth rates using a quartz crystal microbalance with dissipation (QCM-D)

NASA Astrophysics Data System (ADS)

Cao, Bo; Stack, Andrew G.; Steefel, Carl I.; DePaolo, Donald J.; Lammers, Laura N.; Hu, Yandi

2018-02-01

Calcite precipitation plays a significant role in processes such as geological carbon sequestration and toxic metal sequestration and, yet, the rates and mechanisms of calcite growth under close to equilibrium conditions are far from well understood. In this study, a quartz crystal microbalance with dissipation (QCM-D) was used for the first time to measure macroscopic calcite growth rates. Calcite seed crystals were first nucleated and grown on sensors, then growth rates of calcite seed crystals were measured in real-time under close to equilibrium conditions (saturation index, SI = log ({Ca2+}/{CO32-}/Ksp) = 0.01-0.7, where {i} represent ion activities and Ksp = 10-8.48 is the calcite thermodynamic solubility constant). At the end of the experiments, total masses of calcite crystals on sensors measured by QCM-D and inductively coupled plasma mass spectrometry (ICP-MS) were consistent, validating the QCM-D measurements. Calcite growth rates measured by QCM-D were compared with reported macroscopic growth rates measured with auto-titration, ICP-MS, and microbalance. Calcite growth rates measured by QCM-D were also compared with microscopic growth rates measured by atomic force microscopy (AFM) and with rates predicted by two process-based crystal growth models. The discrepancies in growth rates among AFM measurements and model predictions appear to mainly arise from differences in step densities, and the step velocities were consistent among the AFM measurements as well as with both model predictions. Using the predicted steady-state step velocity and the measured step densities, both models predict well the growth rates measured using QCM-D and AFM. This study provides valuable insights into the effects of reactive site densities on calcite growth rate, which may help design future growth models to predict transient-state step densities.

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.

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.

CBT for childhood anxiety disorders: differential changes in selective attention between treatment responders and non-responders.

PubMed

Legerstee, Jeroen S; Tulen, Joke H M; Dierckx, Bram; Treffers, Philip D A; Verhulst, Frank C; Utens, Elisabeth M W J

2010-02-01

This study examined whether treatment response to stepped-care cognitive-behavioural treatment (CBT) is associated with changes in threat-related selective attention and its specific components in a large clinical sample of anxiety-disordered children. Ninety-one children with an anxiety disorder were included in the present study. Children received a standardized stepped-care CBT. Three treatment response groups were distinguished: initial responders (anxiety disorder free after phase one: child-focused CBT), secondary responders (anxiety disorder free after phase two: child-parent-focused CBT), and treatment non-responders. Treatment response was determined using a semi-structured clinical interview. Children performed a pictorial dot-probe task before and after stepped-care CBT (i.e., before phase one and after phase two CBT). Changes in selective attention to severely threatening pictures, but not to mildly threatening pictures, were significantly associated with treatment success. At pre-treatment assessment, initial responders selectively attended away from severely threatening pictures, whereas secondary responders selectively attended toward severely threatening pictures. After stepped-care CBT, initial and secondary responders did not show any selectivity in the attentional processing of severely threatening pictures. Treatment non-responders did not show any changes in selective attention due to CBT. Initial and secondary treatment responders showed a reduction of their predisposition to selectively attend away or toward severely threatening pictures, respectively. Treatment non-responders did not show any changes in selective attention. The pictorial dot-probe task can be considered a potentially valuable tool in assigning children to appropriate treatment formats as well as for monitoring changes in selective attention during the course of CBT.

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.

The influence of graded degrees of chronic hypercapnia on the acute carbon dioxide titration curve

PubMed Central

Goldstein, Marc B.; Gennari, F. John; Schwartz, William B.

1971-01-01

Studies were carried out to determine the influence of the chronic level of arterial carbon dioxide tension upon the buffering response to acute changes in arterial carbon dioxide tension. After chronic adaptation to six levels of arterial CO2 tension, ranging between 35 and 110 mm Hg, unanesthetized dogs underwent acute whole body CO2 titrations. In each instance a linear relationship was observed between the plasma hydrogen ion concentration and the arterial carbon dioxide tension. Because of this linear relationship, it has been convenient to compare the acute buffering responses among dogs in terms of the slope, dH+/dPaco2. With increasing chronic hypercapnia there was a decrease in this slope, i.e. an improvement in buffer capacity, which is expressed by the equation dH+/dPaco2=-0.005 (Paco2)chronic + 0.95. In effect, the ability to defend pH during acute titration virtually doubled as chronic Paco2 increased from 35 to 110 mm Hg. The change in slope, dH+/dPaco2, was the consequence of the following two factors: the rise in plasma bicarbonate concentration which occurs with chronic hypercapnia of increasing severity, and the greater change in bicarbonate concentration which occurred during the acute CO2 titration in the animals with more severe chronic hypercapnia. These findings demonstrate the importance of the acid-base status before acute titration in determining the character of the carbon dioxide titration curve. They also suggest that a quantitative definition of the interplay between acute and chronic hypercapnia in man should assist in the rational analysis of acid-base disorders in chronic pulmonary insufficiency. PMID:5543876

Decreased rates of hypoglycemia following implementation of a comprehensive computerized insulin order set and titration algorithm in the inpatient setting.

PubMed

Sinha Gregory, Naina; Seley, Jane Jeffrie; Gerber, Linda M; Tang, Chin; Brillon, David

2016-12-01

More than one-third of hospitalized patients have hyperglycemia. Despite evidence that improving glycemic control leads to better outcomes, achieving recognized targets remains a challenge. The objective of this study was to evaluate the implementation of a computerized insulin order set and titration algorithm on rates of hypoglycemia and overall inpatient glycemic control. A prospective observational study evaluating the impact of a glycemic order set and titration algorithm in an academic medical center in non-critical care medical and surgical inpatients. The initial intervention was hospital-wide implementation of a comprehensive insulin order set. The secondary intervention was initiation of an insulin titration algorithm in two pilot medicine inpatient units. Point of care testing blood glucose reports were analyzed. These reports included rates of hypoglycemia (BG < 70 mg/dL) and hyperglycemia (BG >200 mg/dL in phase 1, BG > 180 mg/dL in phase 2). In the first phase of the study, implementation of the insulin order set was associated with decreased rates of hypoglycemia (1.92% vs 1.61%; p < 0.001) and increased rates of hyperglycemia (24.02% vs 27.27%; p < 0.001) from 2010 to 2011. In the second phase, addition of a titration algorithm was associated with decreased rates of hypoglycemia (2.57% vs 1.82%; p = 0.039) and increased rates of hyperglycemia (31.76% vs 41.33%; p < 0.001) from 2012 to 2013. A comprehensive computerized insulin order set and titration algorithm significantly decreased rates of hypoglycemia. This significant reduction in hypoglycemia was associated with increased rates of hyperglycemia. Hardwiring the algorithm into the electronic medical record may foster adoption.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol

PubMed Central

García‐Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin‐Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García‐Gutiérrez, Susana

2017-01-01

Abstract Aims Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta‐blockers (BBs), angiotensin‐converting‐enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse‐managed) and control (cardiologist‐managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. Methods We have designed a multicentre (20 hospitals) non‐inferiority randomized controlled trial, including patients with new‐onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II–III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N‐terminal pro B‐type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. Conclusions The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. PMID:29154427

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).…

Plaque assay for African swine fever virus on swine macrophages.

PubMed

Bustos, M J; Nogal, M L; Revilla, Y; Carrascosa, A L

2002-07-01

A plaque assay developed to detect the infection of African Swine Fever Virus on swine macrophages is described. Plaques were generated by all of the virus isolates tested. The method is suitable not only for virus titration but also for the selection of clones in protocols for isolation/purification of recombinant viruses.

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.

Kinetic Titration Series with Biolayer Interferometry

PubMed Central

Frenzel, Daniel; Willbold, Dieter

2014-01-01

Biolayer interferometry is a method to analyze protein interactions in real-time. In this study, we illustrate the usefulness to quantitatively analyze high affinity protein ligand interactions employing a kinetic titration series for characterizing the interactions between two pairs of interaction patterns, in particular immunoglobulin G and protein G B1 as well as scFv IC16 and amyloid beta (1–42). Kinetic titration series are commonly used in surface plasmon resonance and involve sequential injections of analyte over a desired concentration range on a single ligand coated sensor chip without waiting for complete dissociation between the injections. We show that applying this method to biolayer interferometry is straightforward and i) circumvents problems in data evaluation caused by unavoidable sensor differences, ii) saves resources and iii) increases throughput if screening a multitude of different analyte/ligand combinations. PMID:25229647

Kinetic titration series with biolayer interferometry.

PubMed

Frenzel, Daniel; Willbold, Dieter

2014-01-01

Biolayer interferometry is a method to analyze protein interactions in real-time. In this study, we illustrate the usefulness to quantitatively analyze high affinity protein ligand interactions employing a kinetic titration series for characterizing the interactions between two pairs of interaction patterns, in particular immunoglobulin G and protein G B1 as well as scFv IC16 and amyloid beta (1-42). Kinetic titration series are commonly used in surface plasmon resonance and involve sequential injections of analyte over a desired concentration range on a single ligand coated sensor chip without waiting for complete dissociation between the injections. We show that applying this method to biolayer interferometry is straightforward and i) circumvents problems in data evaluation caused by unavoidable sensor differences, ii) saves resources and iii) increases throughput if screening a multitude of different analyte/ligand combinations.

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)

TREATMENT INTENSIFICATION WITH INSULIN DEGLUDEC/INSULIN ASPART TWICE DAILY: RANDOMIZED STUDY TO COMPARE SIMPLE AND STEP-WISE TITRATION ALGORITHMS.

PubMed

Gerety, Gregg; Bebakar, Wan Mohamad Wan; Chaykin, Louis; Ozkaya, Mesut; Macura, Stanislava; Hersløv, Malene Lundgren; Behnke, Thomas

2016-05-01

This 26-week, multicenter, randomized, open-label, parallel-group, treat-to-target trial in adults with type 2 diabetes compared the efficacy and safety of treatment intensification algorithms with twice-daily (BID) insulin degludec/insulin aspart (IDegAsp). Patients randomized 1:1 to IDegAsp BID used either a 'Simple' algorithm (twice-weekly dose adjustments based on a single prebreakfast and pre-evening meal self-monitored plasma glucose [SMPG] measurement; IDegAsp[BIDSimple], n = 136) or a 'Stepwise' algorithm (once-weekly dose adjustments based on the lowest of 3 pre-breakfast and 3 pre-evening meal SMPG values; IDegAsp[BIDStep-wise], n = 136). After 26 weeks, mean change from baseline in glycated hemoglobin (HbA1c) with IDegAsp[BIDSimple] was noninferior to IDegAsp[BIDStep-wise] (-15 mmol/mol versus -14 mmol/mol; 95% confidence interval [CI] upper limit, <4 mmol/mol) (baseline HbA1c: 66.3 mmol/mol IDegAsp[BIDSimple] and 66.6 mmol/mol IDegAsp[BIDStep-wise]). The proportion of patients who achieved HbA1c <7.0% (<53 mmol/mol) at the end of the trial was 66.9% with IDegAsp[BIDSimple] and 62.5% with IDegAsp[BIDStep-wise]. Fasting plasma glucose levels were reduced with each titration algorithm (-1.51 mmol/L IDegAsp[BIDSimple] versus -1.95 mmol/L IDegAsp[BIDStep-wise]). Weight gain was 3.8 kg IDegAsp[BIDSimple] versus 2.6 kg IDegAsp[BIDStep-wise], and rates of overall confirmed hypoglycemia (5.16 episodes per patient-year of exposure [PYE] versus 8.93 PYE) and nocturnal confirmed hypoglycemia (0.78 PYE versus 1.33 PYE) were significantly lower with IDegAsp[BIDStep-wise] versus IDegAsp[BIDSimple]. There were no significant differences in insulin dose increments between groups. Treatment intensification with IDegAsp[BIDSimple] was noninferior to IDegAsp[BIDStep-wise]. Both titration algorithms were well tolerated; however, the more conservative step-wise algorithm led to less weight gain and fewer hypoglycemic episodes. Clinicaltrials.gov: NCT01680341.

Switchable Chiral Selection of Aspartic Acids by Dynamic States of Brushite

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

Jiang, Wenge; Pan, Haihua; Zhang, Zhisen

Here, we show the chiral recognition and separation of aspartic acid (Asp) enantiomers by achiral brushite due to the asymmetries of their dynamical steps in its nonequilibrium states. Growing brushite has a higher adsorption affinity to d-Asp, while l-Asp is predominant on the dissolving brushite surface. Microstructural characterization reveals that chiral selection is mainly attributed to brushite [101] steps, which exhibit two different configurations during crystal growth and dissolution, respectively, with each preferring a distinct enantiomer due to this asymmetry. Because these transition step configurations have different stabilities, they subsequently result in asymmetric adsorption. Furthermore, by varying free energy barriersmore » through solution thermodynamic driving force (i.e., supersaturation), the dominant nonequilibrium intermediate states can be switched and chiral selection regulated. This finding highlights that the dynamic steps can be vital for chiral selection, which may provide a potential pathway for chirality generation through the dynamic nature.« less

Switchable Chiral Selection of Aspartic Acids by Dynamic States of Brushite

DOE PAGES

Jiang, Wenge; Pan, Haihua; Zhang, Zhisen; ...

2017-06-15

Here, we show the chiral recognition and separation of aspartic acid (Asp) enantiomers by achiral brushite due to the asymmetries of their dynamical steps in its nonequilibrium states. Growing brushite has a higher adsorption affinity to d-Asp, while l-Asp is predominant on the dissolving brushite surface. Microstructural characterization reveals that chiral selection is mainly attributed to brushite [101] steps, which exhibit two different configurations during crystal growth and dissolution, respectively, with each preferring a distinct enantiomer due to this asymmetry. Because these transition step configurations have different stabilities, they subsequently result in asymmetric adsorption. Furthermore, by varying free energy barriersmore » through solution thermodynamic driving force (i.e., supersaturation), the dominant nonequilibrium intermediate states can be switched and chiral selection regulated. This finding highlights that the dynamic steps can be vital for chiral selection, which may provide a potential pathway for chirality generation through the dynamic nature.« less

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.

Sustainable Production of o-Xylene from Biomass-Derived Pinacol and Acrolein.

PubMed

Hu, Yancheng; Li, Ning; Li, Guangyi; Wang, Aiqin; Cong, Yu; Wang, Xiaodong; Zhang, Tao

2017-07-21

o-Xylene (OX) is a large-volume commodity chemical that is conventionally produced from fossil fuels. In this study, an efficient and sustainable two-step route is used to produce OX from biomass-derived pinacol and acrolein. In the first step, the phosphotungstic acid (HPW)-catalyzed pinacol dehydration in 1-ethyl-3-methylimidazolium chloride ([emim]Cl) selectively affords 2,3-dimethylbutadiene. The high selectivity of this reaction can be ascribed to the H-bonding interaction between Cl - and the hydroxy group of pinacol. The stabilization of the carbocation intermediate by the surrounding anion Cl - may be another reason for the high selectivity. Notably, the good reusability of the HPW/[emim]Cl system can reduce the waste output and production cost. In the second step, OX is selectively produced by a Diels-Alder reaction of 2,3-dimethylbutadiene and acrolein, followed by a Pd/C-catalyzed decarbonylation/aromatization cascade in a one-pot fashion. The sustainable two-step process efficiently produces renewable OX in 79 % overall yield. Analogously, biomass-derived crotonaldehyde and pinacol can also serve as the feedstocks for the production of 1,2,4-trimethylbenzene. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Calixarene-based potentiometric ion-selective electrodes for silver.

PubMed

O'Connor, K M; Svehla, G; Harris, S J; McKervey, M A

1992-11-01

Four lipophilic sulphur and/or nitrogen containing calixarene derivatives have been tested as ionophores in Ag(I)-selective poly (vinyl chloride) membrane electrodes. All gave acceptable linear responses with one giving a response of 50 mV/dec in the Ag(I) ion activity range 10(-4)-10(-1)M and high selectivity towards other transition metals and sodium and potassium ions. This ionophore was also tested as a membrane coated glassy-carbon electrode where the sensitivity and selectivity of the conventional membrane electrode was found to be repeated. The latter electrode was then used in potentiometric titrations of halide ions with silver nitrate.

Probing the mechanism of proton coupled electron transfer to dioxygen: the oxidative half-reaction of bovine serum amine oxidase.

PubMed

Su, Q; Klinman, J P

1998-09-08

Bovine serum amine oxidase (BSAO) catalyzes the oxidative deamination of primary amines, concomitant with the reduction of molecular oxygen to hydrogen peroxide via a ping-pong mechanism. A protocol has been developed for an analysis of chemical and kinetic mechanisms in the conversion of dioxygen to hydrogen peroxide. Steady-state kinetics show that two groups need to be deprotonated to facilitate the oxidative half-reaction. The pH dependence of Vmax/Km(O2) reveals pKa's of 6.2 +/- 0.3 and 7.0 +/- 0.2, respectively. A pKa of 7.2 +/- 0.1 has been obtained from a titration of anaerobically reduced BSAO using UV-vis spectrophotometry. The near identity of the pKa obtained from the reduced enzyme titration with the second pKa from steady-state kinetics suggests that this second pKa arises from the reduced cofactor. The assignment of pKa is supported by the observed pH dependence for formation of the cofactor semiquinone signal, detected by EPR spectroscopy under anaerobic conditions. To address the nature of rate-limiting steps in the oxidative half-reaction, the solvent isotope effect, viscosity effect, and O-18 isotope effect on Vmax/Km(O2) have been determined. The solvent isotope effect is indistinguishable from unity, ruling out a proton transfer as a rate-determining step. Use of glucose as a solvent viscosogen shows no viscosity effect, indicating that binding of oxygen is not in the rate-determining step. The O-18 kinetic isotope effect is independent of pH with an average value of 18(V/K) = 1.0097 +/- 0. 0010. This has been compared to calculated equilibrium O-18 isotope effects for various dioxygen intermediate species [Tian and Klinman (1993) J. Am. Chem. Soc. 115, 8891], leading to the conclusion that either the first electron transfer to dioxygen or the desorption of product peroxide from a Cu(II)-OOH complex could be the rate-limiting step. The distribution of steady-state enzyme species was, therefore, analyzed through a combination of stopped-flow experiments and analysis of DV and D(V/K) for benzylamine oxidation. We conclude that the major species accumulating in the steady state are the oxidized cofactor-substrate Schiff base complex and the reduced, aminoquinol form of cofactor. These data rule out a slow release of product hydroperoxide from the aminoquinone form of enzyme, leading to the conclusion that the first electron transfer from substrate-reduced cofactor to dioxygen is the rate-determining step in the oxidative half-reaction. This step is also estimated to be 40% rate-limiting in kcat. An important mechanistic conclusion from this study is that dioxygen binding is a separate step from the rate-limiting electron-transfer step to form superoxide. On the basis of a recently determined X-ray structure for the active form of a yeast amine oxidase from Hansenula polymorpha [Li et al. (1998) Structure 6, 293], a hydrophobic space has been identified near the O-2 position of reduced cofactor as the putative dioxygen binding site. Movement of superoxide from this site onto the Cu(II) at the active site may occur prior to further electron transfer from cofactor to superoxide.

A new half-condensed Schiff base compound: highly selective and sensitive pH-responsive fluorescent sensor.

PubMed

Saha, Uday Chand; Dhara, Koushik; Chattopadhyay, Basab; Mandal, Sushil Kumar; Mondal, Swastik; Sen, Supriti; Mukherjee, Monika; van Smaalen, Sander; Chattopadhyay, Pabitra

2011-09-02

A new probe, 3-[(3-benzyloxypyridin-2-ylimino)methyl]-2-hydroxy-5-methylbenzaldehyde (1-H) behaves as a highly selective fluorescent pH sensor in a Britton-Robinson buffer at 25 °C. The pH titrations show a 250-fold increase in fluorescence intensity within the pH range of 4.2 to 8.3 with a pK(a) value of 6.63 which is valuable for studying many of the biological organelles.

Development of Teaching Material Oxidation-Reduction Reactions through Four Steps Teaching Material Development (4S TMD)

NASA Astrophysics Data System (ADS)

Syamsuri, B. S.; Anwar, S.; Sumarna, O.

2017-09-01

This research aims to develop oxidation-reduction reactions (redox) teaching material used the Four Steps Teaching Material Development (4S TMD) method consists of four steps: selection, structuring, characterization and didactical reduction. This paper is the first part of the development of teaching material that includes selection and structuring steps. At the selection step, the development of teaching material begins with the development concept of redox based on curriculum demands, then the development of fundamental concepts sourced from the international textbook, and last is the development of values or skills can be integrated with redox concepts. The results of this selection step are the subject matter of the redox concept and values can be integrated with it. In the structuring step was developed concept map that provide on the relationship between redox concepts; Macro structure that guide systematic on the writing of teaching material; And multiple representations which are the development of teaching material that connection between macroscopic, submicroscopic, and symbolic level representations. The result of the two steps in this first part of the study produced a draft of teaching material. Evaluation of the draft of teaching material is done by an expert lecturer in the field of chemical education to assess the feasibility of teaching material.

An inactivated vaccine made from a U.S. field isolate of porcine epidemic disease virus is immunogenic in pigs as demonstrated by a dose-titration.

PubMed

Collin, Emily A; Anbalagan, Srivishnupriya; Okda, Faten; Batman, Ron; Nelson, Eric; Hause, Ben M

2015-03-15

Porcine epidemic diarrhea virus (PEDV), a highly pathogenic and transmissible virus in swine, was first detected in the U.S. in May, 2013, and has caused tremendous losses to the swine industry. Due to the difficulty in isolating and growing this virus in cell culture, few vaccine studies using cell culture propagated PEDV have been performed on U.S. strains in pigs. Therefore, the objective of this study was to evaluate the humoral immune response to the selected inactivated PEDV vaccine candidate in a dose-titration manner. PEDV was isolated from a pig with diarrhea and complete genome sequencing found >99% nucleotide identity to other U.S. PEDV. Inactivated adjuvanted monovalent vaccines were administered intramuscularly to five week old pigs in a dose titration experimental design, ranging from 6.0-8.0 log10 tissue culture infective dose (TCID50/mL), to evaluate immunogenicity using a fluorescent foci neutralization assay (FFN), fluorescent microsphere immunoassay (FMIA), and enzyme-linked immunosorbent assay (ELISA) on sera. Pigs vaccinated with 8.0 log10 TCID50/mL inactivated virus showed significantly higher FFN titers as well as FMIA and ELISA values than 6.0 log10 TCID50/mL vaccinates and the negative controls. These results demonstrate the immunogenicity of a PEDV inactivated viral vaccine with a U.S. strain via dose-titration. A future vaccination-challenge study would illustrate the efficacy of an inactivated vaccine and help evaluate protective FFN titers and ELISA and FMIA responses.

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

Impact of systolic blood pressure on the safety and tolerability of initiating and up-titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study.

PubMed

Senni, Michele; McMurray, John J V; Wachter, Rolf; McIntyre, Hugh F; Anand, Inder S; Duino, Vincenzo; Sarkar, Arnab; Shi, Victor; Charney, Alan

2018-03-01

The TITRATION trial investigated two strategies to initiate and up-titrate sacubitril/valsartan (LCZ696) to the same target dose, over a condensed (3-week) or conservative (6-week) period, in patients with heart failure with reduced ejection fraction (HFrEF) and systolic blood pressure (SBP) of ≥100 mmHg. This post hoc analysis examined the relationship between baseline SBP at screening and achievement of the target dose of sacubitril/valsartan of 97 mg/103 mg (also termed 'LCZ696 200 mg') twice per day during the study. Patients (n = 498) were categorized in four groups based on SBP at screening: 100-110 mmHg (n = 70); 111-120 mmHg (n = 93); 121-139 mmHg (n = 168) and ≥140 mmHg (n = 167). Overall, 72.7%, 76.1%, 85.6% and 82.9%, respectively, of patients in these SBP categories achieved and maintained the target dose of sacubitril/valsartan without down-titration/dose interruption over 12 weeks ('treatment success'). Compared with patients with SBP of 100-110 mmHg, rates of treatment success among patients in the higher SBP groups [111-120 mmHg (P = 0.96); 121-139 mmHg (P = 0.06) and ≥140 mmHg (P = 0.25)] did not differ significantly. A higher percentage of patients with lower SBP (100-110 mmHg) achieved treatment success with gradual up-titration (6 weeks) (∼80%) than with rapid up-titration (∼69%). Similar findings were observed with regard to 'tolerability success' (maintenance of the target dose for at least the final 2 weeks prior to study completion). Hypotension occurred more frequently in patients with lower SBP. The majority of patients (>80%) with SBP of ≥100 mmHg achieved and maintained the target dose of sacubitril/valsartan if the treatment was titrated gradually. These findings suggest that low SBP should not prevent clinicians from considering the initiation of sacubitril/valsartan. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

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.

Preliminary findings on the correlation of saliva pH, buffering capacity, flow rate and consistency in relation to waterpipe tobacco smoking

PubMed Central

Khemiss, Mehdi; Ben Khelifa, Mohamed; Ben Saad, Helmi

2017-01-01

ABSTRACT The aim of the present comparative study was to compare some salivary characteristics between exclusive waterpipe smokers (EWPS) and non-smokers. 72 males (36 EWPS) were recruited. The volume of stimulated saliva was determined and divided by the duration of saliva collection. The pH was measured directly using a pH meter. The buffering capacity was determined using a quantitative method which involved the addition of 10 µl HCl. Up to a total of 160 µL was titrated up to obtain a pH titration curve. At 50 µL of titrated HCl, buffering capacity was ranked into three categories: high, medium and low. EWPS and non-smoker groups had similar flow rates (1.81 ± 0.79 and 1.78 ± 1.14 mL min-1) and similar baseline pH (6.60 ± 0.37 and 6.76 ± 0.39). Statistically significant differences in the two groups’ pH were observed from 30 to 160 µL of titrated up HCl. At 50 µL of titrated up HCl, the EWPS group compared to the non-smoker group had a significantly higher pH (4.79 ± 0.72 vs. 5.32 ± 0.79). To conclude, waterpipe tobacco smoking alters the buffering capacity but does not alter either salivary flow rates or the baseline pH and consistency. PMID:28266252

Deep brain stimulation for movement disorders.

PubMed

Thevathasan, Wesley; Gregory, Ralph

2010-02-01

Deep brain stimulation is now considered a routine treatment option for selected patients with advanced Parkinson's disease, primary segmental and generalised dystonia, and essential tremor. The neurosurgeon is responsible for the accurate and safe placement of the electrodes and the neurologist for the careful selection of patients and titration of medication against the effects of stimulation. A multidisciplinary team approach involving specialist nurses, neuropsychologists and neurophysiologists is required for a successful outcome. In this article we will summarise the key points in patient selection, provide an overview of the surgical technique, and discuss the beneficial and adverse outcomes that can occur.

Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy

PubMed Central

Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

2016-01-01

An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman. PMID:27606116

A comparison of cationic polymerization and esterification for end-point detection in the catalytic thermometric titration of organic bases.

PubMed

J Greenhow, E; Viñas, P

1984-08-01

A systematic comparison has been made of two indicator systems for the non-aqueous catalytic thermometric titration of strong and weak organic bases. The indicator reagents, alpha-methylstyrene and mixtures of acetic anhydride and hydroxy compounds, are shown to give results (for 14 representative bases) which do not diner significantly in coefficient of variation or titration error. Calibration graphs for all the samples, in the range 0.01-0.1 meq, are linear, with correlation coefficients of 0.995 or better. Aniline, benzylamine, n-butylamine, morpholine, pyrrole, l-dopa, alpha-methyl-l-dopa, dl-alpha-alanine, dl-leucine and l-cysteine cannot be determined when acetic anhydride is present in the sample solution, but some primary and second amines can. This is explained in terms of rates of acetylation of the amino groups.

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.

Turn on ESPT: novel salicylaldehyde based sensor for biological important fluoride sensing.

PubMed

Liu, Kai; Zhao, Xiaojun; Liu, Qingxiang; Huo, Jianzhong; Fu, Huifang; Wang, Ying

2014-09-05

A novel and simple salicylaldehyde based anion fluorescent sensor 1 has been designed, which can selectively sense fluoride by 'turn on' excited-state intermolecular proton transfer (ESPT). The binding constant and the stoichiometry were obtained by non-linear least-square analysis of the titration curves. Copyright © 2014 Elsevier B.V. All rights reserved.

Understanding Zinc Quantification with Existing and Advanced Ditopic Fluorescent Zinpyr Sensors

PubMed Central

Buccella, Daniela; Horowitz, Joshua A.; Lippard, Stephen J.

2011-01-01

Treatment of aqueous zinc solutions with incremental additions of a ditopic fluorescent sensor of the Zinpyr family, based on pyridine/pyrazine-containing metal recognition units, affords a fluorescence titration curve with a sharp maximum at a sensor:Zn2+ ratio of 0.5 (Zhang, X-a.; Hayes, D.; Smith, S. J.; Friedle, S.; Lippard, S. J. J. Am. Chem Soc. 2008, 130, 15788–15789). This fluorescence response enables the quantification of readily chelatable zinc in biological samples by a simple titration protocol. In the present work a new set of ditopic fluorescence zinc sensors functionalized with pyridine/pyrazine-containing metal chelating units is described, and through detailed studies the principles governing the characteristic “OFF-ON-OFF” fluorescence behavior and quantification capabilities of the family are delineated. Incorporation of carboxylate/ester groups in the 6 position of the fluorescein allows for control of the spatial distribution of the sensor for selective extra- or intracellular imaging of mobile zinc, without introducing significant changes in zinc-binding properties. A combination of spectrophotometric and potentiometric measurements provided a complete description of the H+ and Zn2+ binding properties of the compounds and their correlation with the observed fluorescence profile. The first zinc-binding event has an apparent affinity, K1′, of 1.9–3.1×109 M−1, whereas for coordination of the second Zn2+ ion, responsible for fluorescence turn on, the apparent formation constant K2′ is 5.5–6.9×107 M−1. A detailed chemical and mathematical analysis of the system demonstrated that the difference in emission efficiencies of the dimetalated (LZn2) vs. monometalated (LZn) and metal free (L) forms, a consequence of the combined quenching effects of the two metal-chelating units, significantly influences the shape of the titration curve. The scope of the titration method was investigated mathematically, and a lower boundary for the range of concentrations that can be determined was established as a function of the magnitude of K2′. Our results suggest that the principles governing the response of the ZPP1 series are applicable to other analogues of the Zinpyr family. Moreover, they may guide the design of other ditopic sensors suitable for determining the concentrations of a wide range of mobile metal ions and other chemical signaling agents of relevance in biological systems. PMID:21351756

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.

Titrating versus targeting home care services to frail elderly clients: an application of agency theory and cost-benefit analysis to home care policy.

PubMed

Weissert, William; Chernew, Michael; Hirth, Richard

2003-02-01

The article summarizes the shortcomings of current home care targeting policy, provides a conceptual framework for understanding the sources of its problems, and proposes an alternative resource allocation method. Methods required for different aspects of the study included synthesis of the published literature, regression analysis of risk predictors, and comparison of actual resource allocations with simulated budgets. Problems of imperfect agency ranging from unclear goals and inappropriate incentives to lack of information about the marginal effectiveness of home care could be mitigated with an improved budgeting method that combines client selection and resource allocation. No program can produce its best outcome performance when its goals are unclear and its technology is unstandardized. Titration of care would reallocate resources to maximize marginal benefit for marginal cost.

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.

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,…

Bayesian SEM for Specification Search Problems in Testing Factorial Invariance.

PubMed

Shi, Dexin; Song, Hairong; Liao, Xiaolan; Terry, Robert; Snyder, Lori A

2017-01-01

Specification search problems refer to two important but under-addressed issues in testing for factorial invariance: how to select proper reference indicators and how to locate specific non-invariant parameters. In this study, we propose a two-step procedure to solve these issues. Step 1 is to identify a proper reference indicator using the Bayesian structural equation modeling approach. An item is selected if it is associated with the highest likelihood to be invariant across groups. Step 2 is to locate specific non-invariant parameters, given that a proper reference indicator has already been selected in Step 1. A series of simulation analyses show that the proposed method performs well under a variety of data conditions, and optimal performance is observed under conditions of large magnitude of non-invariance, low proportion of non-invariance, and large sample sizes. We also provide an empirical example to demonstrate the specific procedures to implement the proposed method in applied research. The importance and influences are discussed regarding the choices of informative priors with zero mean and small variances. Extensions and limitations are also pointed out.

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.

The SimpleMix study with biphasic insulin aspart 30: a randomized controlled trial investigating patient-driven titration versus investigator-driven titration.

PubMed

Gao, Yan; Luquez, Cecilia; Lynggaard, Helle; Andersen, Henning; Saboo, Banshi

2014-12-01

The study aimed to confirm the efficacy, through non-inferiority, of patient-driven versus investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) in terms of glycemic control assessed by HbA1c change. SimpleMix was a 20 week, open-label, randomized, two-armed, parallel-group, multicenter study in five countries (Argentina, China, India, Poland, and the UK). Patients with type 2 diabetes were randomized into either patient-driven or investigator-driven BIAsp 30 titration groups. Non-inferiority of patient-driven vs. investigator-driven titration based on change in HbA1c from baseline to week 20 could not be demonstrated. Mean (SE) estimated change from baseline to week 20 was -0.72 (0.08)% in the patient-driven group and -0.97 (0.08)% in the investigator-driven group; estimated difference 0.25% (95% CI: 0.04; 0.46). Estimated mean change (SE) in fasting plasma glucose from baseline to week 20 was similar between groups: -0.94 (0.21) mmol/L for patient-driven and -1.07 (0.22) mmol/L for investigator-driven (difference non-significant). Both treatment arms were well tolerated, and hypoglycemic episode rates were similar between groups, with a rate ratio of 0.77 (95% CI: 0.54; 1.09; p = 0.143) for all hypoglycemic episodes and 0.78 (95% CI: 0.42; 1.43; p = 0.417) for nocturnal hypoglycemic episodes. Non-inferiority of patient-driven versus investigator-driven titration with regard to change from baseline to end-of-treatment HbA1c could not be confirmed. It is possible that a clinic visit 12 weeks after intensification of treatment with BIAsp 30 in patients with type 2 diabetes inadequately treated with basal insulin may benefit patient-driven titration of BIAsp 30. A limitation of the study was the relatively small number of patients recruited in each country, which does not allow country-specific analyses to be performed. Overall, treatment with BIAsp 30 was well tolerated in both treatment groups.

Laser isotope separation of erbium and other isotopes

DOEpatents

Haynam, Christopher A.; Worden, Earl F.

1995-01-01

Laser isotope separation is accomplished using at least two photoionization pathways of an isotope simultaneously, where each pathway comprises two or more transition steps. This separation method has been applied to the selective photoionization of erbium isotopes, particularly for the enrichment of .sup.167 Er. The hyperfine structure of .sup.167 Er was used to find two three-step photoionization pathways having a common upper energy level.

Applications of step-selection functions in ecology and conservation.

PubMed

Thurfjell, Henrik; Ciuti, Simone; Boyce, Mark S

2014-01-01

Recent progress in positioning technology facilitates the collection of massive amounts of sequential spatial data on animals. This has led to new opportunities and challenges when investigating animal movement behaviour and habitat selection. Tools like Step Selection Functions (SSFs) are relatively new powerful models for studying resource selection by animals moving through the landscape. SSFs compare environmental attributes of observed steps (the linear segment between two consecutive observations of position) with alternative random steps taken from the same starting point. SSFs have been used to study habitat selection, human-wildlife interactions, movement corridors, and dispersal behaviours in animals. SSFs also have the potential to depict resource selection at multiple spatial and temporal scales. There are several aspects of SSFs where consensus has not yet been reached such as how to analyse the data, when to consider habitat covariates along linear paths between observations rather than at their endpoints, how many random steps should be considered to measure availability, and how to account for individual variation. In this review we aim to address all these issues, as well as to highlight weak features of this modelling approach that should be developed by further research. Finally, we suggest that SSFs could be integrated with state-space models to classify behavioural states when estimating SSFs.

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…

Simple and Automated Coulometric Titration of Acid Using Nonisolated Electrodes

ERIC Educational Resources Information Center

Kuntzleman, Thomas S.; Kenney, Joshua B.; Hasbrouck, Scott; Collins, Michael J.; Amend, John R.

2011-01-01

Coulometric titrations involve the quantification of analyte by measurements of current and time. In most coulometric titrations, the anode and cathode are placed in isolated cells that are connected by a salt bridge. By contrast, the experiments described here involve coulometric titrations (of acidic protons in solution) using a silver anode 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.

Chromophore Structure of Photochromic Fluorescent Protein Dronpa: Acid-Base Equilibrium of Two Cis Configurations.

PubMed

Higashino, Asuka; Mizuno, Misao; Mizutani, Yasuhisa

2016-04-07

Dronpa is a novel photochromic fluorescent protein that exhibits fast response to light. The present article is the first report of the resonance and preresonance Raman spectra of Dronpa. We used the intensity and frequency of Raman bands to determine the structure of the Dronpa chromophore in two thermally stable photochromic states. The acid-base equilibrium in one photochromic state was observed by spectroscopic pH titration. The Raman spectra revealed that the chromophore in this state shows a protonation/deprotonation transition with a pKa of 5.2 ± 0.3 and maintains the cis configuration. The observed resonance Raman bands showed that the other photochromic state of the chromophore is in a trans configuration. The results demonstrate that Raman bands selectively enhanced for the chromophore yield valuable information on the molecular structure of the chromophore in photochromic fluorescent proteins after careful elimination of the fluorescence background.

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.

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

Rioux, Robert M.

In this work, we have primarily utilized isothermal titration calorimetry (ITC) and complimentary catalyst characterization techniques to study and assess the impact of solution conditions (i.e., solid-liquid) interface on the synthesis of heterogeneous and electro-catalysts. Isothermal titration calorimetry is well-known technique from biochemistry/physics, but has been applied to a far lesser extent to characterize buried solid-liquid interfaces in materials science. We demonstrate the utility and unique information provided by ITC for two distinct catalytic systems. We explored the thermodynamics associated catalyst synthesis for two systems: (i) ion-exchange or strong electrostatic adsorption for Pt and Pd salts on silica and aluminamore » materials (ii) adsorption to provide covalent attachment of metal and metal-oxo clusters to Dion-Jacobsen perovskite materials.« less

Financial technical indicator based on chaotic bagging predictors for adaptive stock selection in Japanese and American markets

NASA Astrophysics Data System (ADS)

Suzuki, Tomoya; Ohkura, Yuushi

2016-01-01

In order to examine the predictability and profitability of financial markets, we introduce three ideas to improve the traditional technical analysis to detect investment timings more quickly. Firstly, a nonlinear prediction model is considered as an effective way to enhance this detection power by learning complex behavioral patterns hidden in financial markets. Secondly, the bagging algorithm can be applied to quantify the confidence in predictions and compose new technical indicators. Thirdly, we also introduce how to select more profitable stocks to improve investment performance by the two-step selection: the first step selects more predictable stocks during the learning period, and then the second step adaptively and dynamically selects the most confident stock showing the most significant technical signal in each investment. Finally, some investment simulations based on real financial data show that these ideas are successful in overcoming complex financial markets.

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

Quantum chemical investigation on photodegradation mechanisms of sulfamethoxypyridazine with dissolved inorganic matter and hydroxyl radical.

PubMed

Shah, Shaheen; Hao, Ce

2017-07-01

Sulfamethoxypyridazine (SMP) is one of the commonly used sulfonamide antibiotics (SAs). SAs are mainly studied to undergo triplet-sensitized photodegradation in water under natural sunlight with other coexisting aquatic environmental organic pollutants. In this work, SMP was selected as a representative of SAs. We studied the mechanisms of triplet-sensitized photodegradation of SMP and the influence of selected dissolved inorganic matter, i.e., anions (Br - , Cl - , and NO 3 - ) and cations ions (Ca 2+ , Mg 2+ , and Zn 2+ ) on SMP photodegradation mechanism by quantum chemical methods. In addition, the degradation mechanisms of SMP by hydroxyl radical (OH) were also investigated. The creation of SO 2 extrusion product was accessed with two different energy pathways (pathway-1 and pathway-2) by following two steps (step-I and step-II) in the triplet-sensitized photodegradation of SMP. Due to low activation energy, the pathway-1 was considered as the main pathway to obtain SO 2 extrusion product. Step-II of pathway-1 was measured to be the rate-limiting step (RLS) of SMP photodegradation mechanism and the effect of the selected anions and cations was estimated for this step. All selected anions and cations promoted photodegradation of SMP by dropping the activation energy of pathway-1. The estimated low activation energies of different degradation pathways of SMP with OH radical indicate that OH radical is a very powerful oxidizing agent for SMP degradation via attack through benzene derivative and pyridazine derivative ring. Copyright © 2016. Published by Elsevier B.V.

Food acid content and erosive potential of sugar-free confections.

PubMed

Shen, P; Walker, G D; Yuan, Y; Reynolds, C; Stacey, M A; Reynolds, E C

2017-06-01

Dental erosion is an increasingly prevalent problem associated with frequent consumption of acidic foods and beverages. The aim of this study was to measure the food acid content and the erosive potential of a variety of sugar-free confections. Thirty sugar-free confections were selected and extracts analysed to determine pH, titratable acidity, chemical composition and apparent degree of saturation with respect to apatite. The effect of the sugar-free confections in artificial saliva on human enamel was determined in an in vitro dental erosion assay using change in surface microhardness. The change in surface microhardness was used to categorize the confections as high, moderate or low erosive potential. Seventeen of the 30 sugar-free confections were found to contain high concentrations of food acids, exhibit low pH and high titratable acidity and have high erosive potential. Significant correlations were found between the dental erosive potential (change in enamel surface microhardness) and pH and titratable acidity of the confections. Ten of these high erosive potential confections displayed dental messages on the packaging suggesting they were safe for teeth. Many sugar-free confections, even some with 'Toothfriendly' messages on the product label, contain high contents of food acids and have erosive potential. © 2017 Australian Dental Association.

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.

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.

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

Interaction between lactic acid bacteria and yeasts in airag, an alcoholic fermented milk.

PubMed

Sudun; Wulijideligen; Arakawa, Kensuke; Miyamoto, Mari; Miyamoto, Taku

2013-01-01

The interaction between nine lactic acid bacteria (LAB) and five yeast strains isolated from airag of Inner Mongolia Autonomic Region, China was investigated. Three representative LAB and two yeasts showed symbioses were selected and incubated in 10% (w/v) reconstituted skim milk as single and mixed cultures to measure viable count, titratable acidity, ethanol and sugar content every 24 h for 1 week. LAB and yeasts showed high viable counts in the mixed cultures compared to the single cultures. Titratable acidity of the mixed cultures was obviously enhanced compared with that of the single cultures, except for the combinations of Lactobacillus reuteri 940B3 with Saccharomyces cerevisiae 4C and Lactobacillus helveticus 130B4 with Candida kefyr 2Y305. C. kefyr 2Y305 produced large amounts of ethanol (maximum 1.35 g/L), whereas non-lactose-fermenting S. cerevisiae 4C produced large amounts of ethanol only in the mixed cultures. Total glucose and galactose content increased while lactose content decreased in the single cultures of Leuconostoc mesenteroides 6B2081 and Lb. helveticus 130B4. However, both glucose and galactose were completely consumed and lactose was markedly reduced in the mixed cultures with yeasts. The result suggests that yeasts utilize glucose and galactose produced by LAB lactase to promote cell growth. © 2012 The Authors. Animal Science Journal © 2012 Japanese Society of Animal Science.

Rapid Titration of Measles and Other Viruses: Optimization with Determination of Replication Cycle Length

PubMed Central

Grigorov, Boyan; Rabilloud, Jessica; Lawrence, Philip; Gerlier, Denis

2011-01-01

Background Measles virus (MV) is a member of the Paramyxoviridae family and an important human pathogen causing strong immunosuppression in affected individuals and a considerable number of deaths worldwide. Currently, measles is a re-emerging disease in developed countries. MV is usually quantified in infectious units as determined by limiting dilution and counting of plaque forming unit either directly (PFU method) or indirectly from random distribution in microwells (TCID50 method). Both methods are time-consuming (up to several days), cumbersome and, in the case of the PFU assay, possibly operator dependent. Methods/Findings A rapid, optimized, accurate, and reliable technique for titration of measles virus was developed based on the detection of virus infected cells by flow cytometry, single round of infection and titer calculation according to the Poisson's law. The kinetics follow up of the number of infected cells after infection with serial dilutions of a virus allowed estimation of the duration of the replication cycle, and consequently, the optimal infection time. The assay was set up to quantify measles virus, vesicular stomatitis virus (VSV), and human immunodeficiency virus type 1 (HIV-1) using antibody labeling of viral glycoprotein, virus encoded fluorescent reporter protein and an inducible fluorescent-reporter cell line, respectively. Conclusion Overall, performing the assay takes only 24–30 hours for MV strains, 12 hours for VSV, and 52 hours for HIV-1. The step-by-step procedure we have set up can be, in principle, applicable to accurately quantify any virus including lentiviral vectors, provided that a virus encoded gene product can be detected by flow cytometry. PMID:21915289

Resistant hypertension optimal treatment trial: a randomized controlled trial.

PubMed

Krieger, Eduardo M; Drager, Luciano F; Giorgi, Dante Marcelo Artigas; Krieger, Jose Eduardo; Pereira, Alexandre Costa; Barreto-Filho, José Augusto Soares; da Rocha Nogueira, Armando; Mill, José Geraldo

2014-01-01

The prevalence of resistant hypertension (ReHy) is not well established. Furthermore, diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and calcium channel blockers are largely used as the first 3-drug combinations for treating ReHy. However, the fourth drug to be added to the triple regimen is still controversial and guided by empirical choices. We sought (1) to determine the prevalence of ReHy in patients with stage II hypertension; (2) to compare the effects of spironolactone vs clonidine, when added to the triple regimen; and (3) to evaluate the role of measuring sympathetic and renin-angiotensin-aldosterone activities in predicting blood pressure response to spironolactone or clonidine. The Resistant Hypertension Optimal Treatment (ReHOT) study (ClinicalTrials.gov NCT01643434) is a prospective, multicenter, randomized trial comprising 26 sites in Brazil. In step 1, 2000 patients will be treated according to hypertension guidelines for 12 weeks, to detect the prevalence of ReHy. Medical therapy adherence will be checked by pill count monitoring. In step 2, patients with confirmed ReHy will be randomized to an open label 3-month treatment with spironolactone (titrating dose, 12.5-50 mg once daily) or clonidine (titrating dose, 0.1-0.3 mg twice daily). The primary endpoint is the effective control of blood pressure after a 12-week randomized period of treatment. The ReHOT study will disseminate results about the prevalence of ReHy in stage II hypertension and the comparison of spironolactone vs clonidine for blood pressure control in patients with ReHy under 3-drug standard regimen. © 2013 Wiley Periodicals, Inc.

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

Neural networks for vertical microcode compaction

NASA Astrophysics Data System (ADS)

Chu, Pong P.

1992-09-01

Neural networks provide an alternative way to solve complex optimization problems. Instead of performing a program of instructions sequentially as in a traditional computer, neural network model explores many competing hypotheses simultaneously using its massively parallel net. The paper shows how to use the neural network approach to perform vertical micro-code compaction for a micro-programmed control unit. The compaction procedure includes two basic steps. The first step determines the compatibility classes and the second step selects a minimal subset to cover the control signals. Since the selection process is an NP- complete problem, to find an optimal solution is impractical. In this study, we employ a customized neural network to obtain the minimal subset. We first formalize this problem, and then define an `energy function' and map it to a two-layer fully connected neural network. The modified network has two types of neurons and can always obtain a valid solution.

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)

Acidic beverages increase the risk of in vitro tooth erosion

PubMed Central

Ehlen, Leslie A.; Marshall, Teresa A.; Qian, Fang; Wefel, James S.; Warren, John J.

2008-01-01

Acidic beverages are thought to increase the potential for dental erosion. We report pH and titratable acidities (i.e., quantity of base required to bring a solution to neutral pH) of beverages popular in the United States and lesion depths in enamel and root surfaces following beverage exposure, and we describe associations among pH, titratable acidity and both enamel and root erosive lesion depths. The pH of 100% juices, regular sodas, diet sodas and sports drinks upon opening, and the titratable acidity both upon opening and after 60 minutes of stirring were measured. Enamel and root surfaces of healthy permanent molars and premolars were exposed to individual beverages (4 enamel and 4 root surfaces per beverage) for 25 hours and erosion was measured. Statistical analyses included two-sample t-tests, analyses of variance with post hoc Tukey’s studentized range test; and Spearman rank correlation coefficients. All beverages were acidic; the titratable acidity of energy drinks was greater than regular sodas and diet sodas which were greater than 100% juices and sports drinks (P<0.05). Enamel lesion depths following beverage exposures were greatest for Gatorade® followed by Red Bull® and Coke® which were greater than Diet Coke® and 100% apple juice (P <0.05). Root lesion depths were greatest for Gatorade® followed by Red Bull®, Coke®, 100% apple juice and Diet Coke® (P<0.05). Lesion depths were not associated with pH or titratable acidity. Beverages popular in the United States can produce dental erosion. PMID:19083423

Interactive Design Strategy for a Multi-Functional PAMAM Dendrimer-Based Nano-Therapeutic Using Computational Models and Experimental Analysis

PubMed Central

Lee, Inhan; Williams, Christopher R.; Athey, Brian D.; Baker, James R.

2010-01-01

Molecular dynamics simulations of nano-therapeutics as a final product and of all intermediates in the process of generating a multi-functional nano-therapeutic based on a poly(amidoamine) (PAMAM) dendrimer were performed along with chemical analyses of each of them. The actual structures of the dendrimers were predicted, based on potentiometric titration, gel permeation chromatography, and NMR. The chemical analyses determined the numbers of functional molecules, based on the actual structure of the dendrimer. Molecular dynamics simulations calculated the configurations of the intermediates and the radial distributions of functional molecules, based on their numbers. This interactive process between the simulation results and the chemical analyses provided a further strategy to design the next reaction steps and to gain insight into the products at each chemical reaction step. PMID:20700476

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

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol.

PubMed

Oyanguren, Juana; García-Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin-Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García-Gutiérrez, Susana

2017-11-01

Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta-blockers (BBs), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse-managed) and control (cardiologist-managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. We have designed a multicentre (20 hospitals) non-inferiority randomized controlled trial, including patients with new-onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II-III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N-terminal pro B-type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Efficacy and safety of down-titration versus continuation strategies of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis with low disease activity or in remission: a systematic review and meta-analysis.

PubMed

Jiang, Mei; Ren, Feifeng; Zheng, Yaning; Yan, Ruyu; Huang, Wenhan; Xia, Ning; Luo, Lei; Zhou, Jun; Tang, Lin

2017-01-01

To evaluate the efficacy and safety of down-titration (dose reduction/tapering) strategies compared with continuation of biological disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who achieved and maintained low disease activity or remission. We searched the following electronic database up to March 2016: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and conference proceedings of the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR). Our meta-analysis included randomized controlled trials (RCTs) of RA patients with low disease activity or in remission that compared down-titration treatment with continuation treatment. Data on flare, defined as a 28-joint Disease Activity Score of ≥3.2, had to have been reported. Outcomes on efficacy or safety were collected. Of 1136 references identified, five RCTs (total, 771 participants) were included. The incidence of disease relapse in the down-titration and continuation groups was similar (risk ratio (RR)=1.14, 95% CI=0.88-1.49). There was no statistical difference in the number of serious adverse events (RR=1.15, 95% CI=0.53-2.49). Withdrawals due to inefficacy or toxicity were similar between groups and no clinically meaningful difference in efficacy outcomes was observed by continuation treatment. Our findings indicated that continuing a standard dose of biological DMARDs in patients with low disease activity conveyed no significant benefit as compared with down-titration therapy, suggesting that a down-titration strategy is as effective as a continuation strategy. Since the number of trials meeting the criteria for this meta-analysis was relatively low, future analyses with additional prospective RCTs are required to compare other biological agents and evaluate the long-term efficacy of these two strategies.

ASSESSMENT OF ATTENTION THRESHOLD IN RATS BY TITRATION OF VISUAL CUE DURATION DURING THE FIVE CHOICE SERIAL REACTION TIME TASK

PubMed Central

Martin, Thomas J.; Grigg, Amanda; Kim, Susy A.; Ririe, Douglas G.; Eisenach, James C.

2014-01-01

Background The 5 choice serial reaction time task (5CSRTT) is commonly used to assess attention in rodents. We sought to develop a variant of the 5CSRTT that would speed training to objective success criteria, and to test whether this variant could determine attention capability in each subject. New Method Fisher 344 rats were trained to perform a variant of the 5CSRTT in which the duration of visual cue presentation (cue duration) was titrated between trials based upon performance. The cue duration was decreased when the subject made a correct response, or increased with incorrect responses or omissions. Additionally, test day challenges were provided consisting of lengthening the intertrial interval and inclusion of a visual distracting stimulus. Results Rats readily titrated the cue duration to less than 1 sec in 25 training sessions or less (mean ± SEM, 22.9 ± 0.7), and the median cue duration (MCD) was calculated as a measure of attention threshold. Increasing the intertrial interval increased premature responses, decreased the number of trials completed, and increased the MCD. Decreasing the intertrial interval and time allotted for consuming the food reward demonstrated that a minimum of 3.5 sec is required for rats to consume two food pellets and successfully attend to the next trial. Visual distraction in the form of a 3 Hz flashing light increased the MCD and both premature and time out responses. Comparison with existing method The titration variant of the 5CSRTT is a useful method that dynamically measures attention threshold across a wide range of subject performance, and significantly decreases the time required for training. Task challenges produce similar effects in the titration method as reported for the classical procedure. Conclusions The titration 5CSRTT method is an efficient training procedure for assessing attention and can be utilized to assess the limit in performance ability across subjects and various schedule manipulations. PMID:25528113

Development of Conductivity Method as an Alternative to Titration for Hydrolytic Resistance Testing Used for Evaluation of Glass Vials Used in Pharmaceutical Industry.

PubMed

Fujimori, Kiyoshi; Lee, Hans; Phillips, Joseph; Nashed-Samuel, Yasser

The European Pharmacopeia surface test to analyze the hydrolytic resistance is a common industrial method to understand and ensure the quality of produced glass vials. Hydrolytic resistance is evaluated by calculating the alkalinity of water extract from autoclaved vials by titration. As an alternative to this titration technique, a conductivity technique was assessed, which directly measures the ions in the water extract. A conductivity meter with a 12 mm diameter electrode was calibrated with a 100 μS/cm conductivity standard and carryover minimized by rinsing the probe in a water beaker per analysis. The limit of quantification at 1 μS/cm was determined as having a signal-to-noise ratio of 3 compared with the water blank. The conductivity method was selective for glass-composing elements (boron, sodium, aluminum, silicon, potassium, and calcium) within the vial extract. Accuracies of spiked conductivity standard within the range of 1 to 100 μS/cm were ±7% and had linearity with coefficient of determination (R 2 ) of ≥0.9999. Intraday precision had a relative standard deviation (RSD) (n = 5) of ≤6% for spiked conductivity standard within the range of 1 to 100 μS/cm. Interday precision had a RSD (n = 4) of ≤6% for 10 vials from three glass vial lots. Conductivity of water extracts from nine sets of seven lots of glass vials had a precise linear relationship [R 2 = 0.9876, RSD = 1% (n = 9)] with titration volumes of the same lots. Conductivity results in μS/cm could be converted to titration volumes in milliliters by a conversion factor of 0.0275. The simplicity, sample stability, and individual vial analysis of the conductivity technique were more advantageous than the current titration technique. The quality of glass vials used as primary containers in the pharmaceutical industry is of concern due to recent observations of glass flake-like delamination, or lamellae, under specific storage conditions. The current European Pharmacopoeia method to assess glass vial quality utilizes acid titration of vial extract pools to determine hydrolytic resistance or alkalinity. As an alternative to the European Pharmacopoeia method, the vial extracts were analyzed for conductivity, which directly determines the level of ions that were readily extracted from the vial surfaces. Lower quality glass would have greater surface defects that lead to higher ions extracted and higher conductivity value. The conductivity method was found to be suitable to measure the ions in water extracts and showed strong correlation with alkalinity. The advantage of the conductivity method over the alkalinity method was greater ease, lower volume requirements, stability, and flexibility in analysis. © PDA, Inc. 2017.

Ammonia Transporters and Their Role in Acid-Base Balance

PubMed Central

2017-01-01

Acid-base homeostasis is critical to maintenance of normal health. Renal ammonia excretion is the quantitatively predominant component of renal net acid excretion, both under basal conditions and in response to acid-base disturbances. Although titratable acid excretion also contributes to renal net acid excretion, the quantitative contribution of titratable acid excretion is less than that of ammonia under basal conditions and is only a minor component of the adaptive response to acid-base disturbances. In contrast to other urinary solutes, ammonia is produced in the kidney and then is selectively transported either into the urine or the renal vein. The proportion of ammonia that the kidney produces that is excreted in the urine varies dramatically in response to physiological stimuli, and only urinary ammonia excretion contributes to acid-base homeostasis. As a result, selective and regulated renal ammonia transport by renal epithelial cells is central to acid-base homeostasis. Both molecular forms of ammonia, NH3 and NH4+, are transported by specific proteins, and regulation of these transport processes determines the eventual fate of the ammonia produced. In this review, we discuss these issues, and then discuss in detail the specific proteins involved in renal epithelial cell ammonia transport. PMID:28151423

A multi writable thiophene-based selective and reversible chromogenic fluoride probe with dual -NH functionality.

PubMed

Vishwakarma, Siddharth; Kumar, Ajit; Pandey, Abha; Upadhyay, K K

2017-01-05

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 (1)H 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±0.069×10(8)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. Copyright © 2016 Elsevier B.V. All rights reserved.

Continuous track paths reveal additive evidence integration in multistep decision making.

PubMed

Buc Calderon, Cristian; Dewulf, Myrtille; Gevers, Wim; Verguts, Tom

2017-10-03

Multistep decision making pervades daily life, but its underlying mechanisms remain obscure. We distinguish four prominent models of multistep decision making, namely serial stage, hierarchical evidence integration, hierarchical leaky competing accumulation (HLCA), and probabilistic evidence integration (PEI). To empirically disentangle these models, we design a two-step reward-based decision paradigm and implement it in a reaching task experiment. In a first step, participants choose between two potential upcoming choices, each associated with two rewards. In a second step, participants choose between the two rewards selected in the first step. Strikingly, as predicted by the HLCA and PEI models, the first-step decision dynamics were initially biased toward the choice representing the highest sum/mean before being redirected toward the choice representing the maximal reward (i.e., initial dip). Only HLCA and PEI predicted this initial dip, suggesting that first-step decision dynamics depend on additive integration of competing second-step choices. Our data suggest that potential future outcomes are progressively unraveled during multistep decision making.

Using a Fluorescent Cytosine Analogue tC[superscript o] To Probe the Effect of the Y567 to Ala Substitution on the Preinsertion Steps of dNMP Incorporation by RB69 DNA Polymerase

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

Xia, Shuangluo; Beckman, Jeff; Wang, Jimin

2012-10-10

Residues in the nascent base pair binding pocket (NBP) of bacteriophage RB69 DNA polymerase (RB69pol) are responsible for base discrimination. Replacing Tyr567 with Ala leads to greater flexibility in the NBP, increasing the probability of misincorporation. We used the fluorescent cytosine analogue, 1,3-diaza-2-oxophenoxazine (tC{sup o}), to identify preinsertion step(s) altered by NBP flexibility. When tC{sup o} is the templating base in a wild-type (wt) RB69pol ternary complex, its fluorescence is quenched only in the presence of dGTP. However, with the RB69pol Y567A mutant, the fluorescence of tC{sup o} is also quenched in the presence of dATP. We determined the crystalmore » structure of the dATP/tC{sup o}-containing ternary complex of the RB69pol Y567A mutant at 1.9 {angstrom} resolution and found that the incoming dATP formed two hydrogen bonds with an imino-tautomerized form of tC{sup o}. Stabilization of the dATP/tC{sup o} base pair involved movement of the tC{sup o} backbone sugar into the DNA minor groove and required tilting of the tC{sup o} tricyclic ring to prevent a steric clash with L561. This structure, together with the pre-steady-state kinetic parameters and dNTP binding affinity, estimated from equilibrium fluorescence titrations, suggested that the flexibility of the NBP, provided by the Y567 to Ala substitution, led to a more favorable forward isomerization step resulting in an increase in dNTP binding affinity.« less

Coprecipitation mechanisms and products in manganese oxidation in the presence of cadmium

USGS Publications Warehouse

Hem, J.D.; Lind, Carol J.

1991-01-01

Manganese oxidation products were precipitated in an aerated open-aqueous system where a continuous influx of mixed Mn2+ and Cd2+ solution was supplied and pH was maintained with an automated pH-stat adding dilute NaOH. X-ray diffraction and electron diffraction identified the solids produced as mixtures of Cd2Mn34+O8, Mn2+2Mn4+3O8, MnO2 (ramsdellite), and CdCO3. Mean oxidation numbers of the total precipitated Mn as great as 3.6 were reached during titrations. During subsequent aging in solution, oxidation numbers between 3.8 and 3.9 were reached in some precipitates in less than 40 days. Conditional oxidation rate constants calculated from a crystal-growth equation applied to titration data showed the overall precipitation rate, without considering manganese oxidation state in the precipitate, was increased by a factor of ~4 to ~7 when the mole ratio (Cd/Mn + Cd) of cadmium in the feed solution was 0.40 compared with rate constants for hausmannite (Mn2+Mn23+O4 precipitation under similar conditions but without accessory metals. Kinetic experiments were made to test effects of various Cd/Mn + Cd mole ratios and rates of addition of the feed solution, different temperatures from 5.0 to 35??C, and pH from 8.0 to 9.0. Oxidation rates were slower when the Cd mole ratio was less than 0.40. The rate increased by a factor of ~10 when pH was raised one-half unit. The effect of temperature on the rate constants was also substantial, but the meaning of this is uncertain because the rate of formation of Mn4+ oxide in the absence of Cd or other accessory metals was too slow to be measurable in titration experiments. The increased rate of Mn4+ oxide formation in the presence of Cd2+ can be ascribed to the formation of a labile adsorbed intermediate, CdMn2O4 Int, an analog of hausmannite, formed on precipitate surfaces at the beginning of the oxidation process. The increased lability of this structure, resulting from coordination-chemical behavior of Cd2+ during the titration, causes a rapid second-stage rearrangement and facilitates disproportionation of the Mn3+ ions. The Mn2+ ions thus released provide a positive feedback mechanism that couples the two steps of the conversion of Mn2+ to Mn4+ more closely than is possible when other metal ions besides manganese are not present. During aging of precipitates in contact with solutions, proportions of Cd2Mn3O8 and MnO2 increased at the expense of other precipitate components. ?? 1991.

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.

Laser isotope separation of erbium and other isotopes

DOEpatents

Haynam, C.A.; Worden, E.F.

1995-08-22

Laser isotope separation is accomplished using at least two photoionization pathways of an isotope simultaneously, where each pathway comprises two or more transition steps. This separation method has been applied to the selective photoionization of erbium isotopes, particularly for the enrichment of {sup 167}Er. The hyperfine structure of {sup 167}Er was used to find two three-step photoionization pathways having a common upper energy level. 3 figs.

Hydrogen ion titrations of the anodic and cathodic haemoglobin components of the European eel Anguilla anguilla.

PubMed

Brauner, C J; Weber, R E

1998-09-01

H+ titrations were conducted on the separated haemoglobin components of eel Anguilla anguilla in both the oxygenated and deoxygenated states. In anodic haemoglobin, the addition of GTP, and to a lesser extent C1-, increased the magnitude of the Haldane effect and shifted its maximum value into the in vivo pH range. Of the 22 histidine residues in the anodic component, only approximately seven were titratable, presumably the beta-chain residues at positions 41, 97, 109 and 146 (helical positions C7, FG4, G11 and HC3, respectively). In cathodic haemoglobin, a small negative Haldane effect was observed at pH values between 6.8 and 8.5 which disappeared in the presence of GTP (molar ratio 3:1 GTP:haemoglobin tetramer). GTP had virtually no effect on the buffer value at fixed oxygenation status, and the lowest buffer value was observed at in vivo pH values. No titratable histidine residues were observed in the cathodic component, indicating that all 14 histidines in this component are buried. We conclude that the anodic component, which constitutes two-thirds of the haemoglobin in the eel, plays the predominant role in CO2 transport and pH homeostasis in vivo.

A rapid method for infectivity titration of Andes hantavirus using flow cytometry.

PubMed

Barriga, Gonzalo P; Martínez-Valdebenito, Constanza; Galeno, Héctor; Ferrés, Marcela; Lozach, Pierre-Yves; Tischler, Nicole D

2013-11-01

The focus assay is currently the most commonly used technique for hantavirus titer determination. This method requires an incubation time of between 5 and 11 days to allow the appearance of foci after several rounds of viral infection. The following work presents a rapid Andes virus (ANDV) titration assay, based on viral nucleocapsid protein (N) detection in infected cells by flow cytometry. To this end, an anti-N monoclonal antibody was used that was developed and characterized previously. ANDV N could be detected as early as 6 h post-infection, while viral release was not observed until 24-48 h post-infection. Given that ANDV detection was performed during its first round of infection, a time reduction for titer determination was possible and provided results in only two days. The viral titer was calculated from the percentage of N positive cells and agreed with focus assay titers. Furthermore, the assay was applied to quantify the inhibition of ANDV cell entry by patient sera and by preventing endosome acidification. This novel hantavirus titration assay is a highly quantitative and sensitive tool that facilitates infectivity titration of virus stocks, rapid screening for antiviral drugs, and may be further used to detect and quantify infectious virus in human samples. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

The Acid-Base Titration of a Very Weak Acid: Boric Acid

ERIC Educational Resources Information Center

Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.

2012-01-01

A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

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.

Operator models for delivering municipal solid waste management services in developing countries: Part B: Decision support.

PubMed

Soós, Reka; Whiteman, Andrew D; Wilson, David C; Briciu, Cosmin; Nürnberger, Sofia; Oelz, Barbara; Gunsilius, Ellen; Schwehn, Ekkehard

2017-08-01

This is the second of two papers reporting the results of a major study considering 'operator models' for municipal solid waste management (MSWM) in emerging and developing countries. Part A documents the evidence base, while Part B presents a four-step decision support system for selecting an appropriate operator model in a particular local situation. Step 1 focuses on understanding local problems and framework conditions; Step 2 on formulating and prioritising local objectives; and Step 3 on assessing capacities and conditions, and thus identifying strengths and weaknesses, which underpin selection of the operator model. Step 4A addresses three generic questions, including public versus private operation, inter-municipal co-operation and integration of services. For steps 1-4A, checklists have been developed as decision support tools. Step 4B helps choose locally appropriate models from an evidence-based set of 42 common operator models ( coms); decision support tools here are a detailed catalogue of the coms, setting out advantages and disadvantages of each, and a decision-making flowchart. The decision-making process is iterative, repeating steps 2-4 as required. The advantages of a more formal process include avoiding pre-selection of a particular com known to and favoured by one decision maker, and also its assistance in identifying the possible weaknesses and aspects to consider in the selection and design of operator models. To make the best of whichever operator models are selected, key issues which need to be addressed include the capacity of the public authority as 'client', management in general and financial management in particular.

Web based health surveys: Using a Two Step Heckman model to examine their potential for population health analysis.

PubMed

Morrissey, Karyn; Kinderman, Peter; Pontin, Eleanor; Tai, Sara; Schwannauer, Mathias

2016-08-01

In June 2011 the BBC Lab UK carried out a web-based survey on the causes of mental distress. The 'Stress Test' was launched on 'All in the Mind' a BBC Radio 4 programme and the test's URL was publicised on radio and TV broadcasts, and made available via BBC web pages and social media. Given the large amount of data created, over 32,800 participants, with corresponding diagnosis, demographic and socioeconomic characteristics; the dataset are potentially an important source of data for population based research on depression and anxiety. However, as respondents self-selected to participate in the online survey, the survey may comprise a non-random sample. It may be only individuals that listen to BBC Radio 4 and/or use their website that participated in the survey. In this instance using the Stress Test data for wider population based research may create sample selection bias. Focusing on the depression component of the Stress Test, this paper presents an easy-to-use method, the Two Step Probit Selection Model, to detect and statistically correct selection bias in the Stress Test. Using a Two Step Probit Selection Model; this paper did not find a statistically significant selection on unobserved factors for participants of the Stress Test. That is, survey participants who accessed and completed an online survey are not systematically different from non-participants on the variables of substantive interest. Copyright © 2016 Elsevier Ltd. All rights reserved.

Validation of a polymerase chain reaction aided transcript titration assay (PATTY) for topoisomerase II in lung cancer samples.

PubMed

Dingemans, A M; Van Ark-Otte, J; Smit, E F; Postmus, P E; Giaccone, G

This report describes the validation of a polymerase chain reaction aided transcript titration assay (PATTY) for tumor samples. The results obtained with the PATTY were compared to those of RNase protection in a set of 7 human lung cancer cell lines and in 23 non-small cell lung cancer samples derived from resected patients. Whereas between PATTY and RNase protection assay a good correlation was observed in the cell lines (r = 0.74, p = 0.057), no correlation was observed within the tumor samples (r = 0.06, p = 0.78). This was also the case when only tumors with a high percentage of tumor cells (> 90%) were selected. Although PATTY is a valuable tool to measure mRNA expression in cell lines, our results caution the use of PATTY in human tumor samples without proper validation. The possible causes of these results are discussed.

Strong positive cooperativity in binding to the A3T3 repeat by Hoechst 33258 derivatives attaching the quinoline units at the end of a branched linker.

PubMed

Koda, Hironori; Brazier, John Alan; Onishi, Ippei; Sasaki, Shigeki

2015-08-01

Hoechst 33258 derivatives with additional interacting moieties attached at the ends of branched linkers were synthesized, and their DNA binding properties were investigated with regard to the A3T3 repeat by measuring fluorescence spectra. The binding property of the ligand was investigated by fluorescence titration, and the titration data were analyzed using the McGhee-von Hippel method. Ligand 6Q with the quinolin-6-yloxyacetyl group and Ligand IQ with isoquinolin-6-yloxyacetyl group at the ends of the branched linkers exhibit highly positive cooperativity for the DNA having 5 A3T3 sites with 3 base-insertions between them with sequence selectivity. The strategy developed in this study may be generally applicable for designing ligands for repetitive DNA sequences. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural characterization of osmoregulator peptides from the brain of the leech Theromyzon tessulatum: IPEPYVWD and IPEPYVWD-amide.

PubMed

Salzet, M; Vandenbulcke, F; Verger-Bocquet, M

1996-12-31

Neurons immunoreactive to an antiserum (a-OT) directed specifically against the C-terminal part (prolyl-leucyl-glycinamide) of vertebrate oxytocin (OT) were detected in the brain of the leech Theromyzon tessulatum. With high pressure gel permeation chromatography followed by reversed-phase HPLC on brain extracts, evidence was given of the presence of three peptides (P1, P2, P3) immunoreactive to a-OT. Results of injection experiments in T. tessulatum and of titrations of each peptide at the different physiological stages of the animals which showed a peak in peptide P1 amount at stage 3B, indicated that P1 is the active OT-like peptide. Using three steps of reversed-phase HPLC, Edman degradation and electrospray mass spectrometry, two sequences for P1 (IPEPYVWD and IPEPYVWD-amide) were found. These peptides differ from peptides to the oxytocin/vasopressin family and are unique in the animal kingdom. Confirmation of their action on the hydric balance and their distribution in the CNS were presented.

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements

PubMed Central

2012-01-01

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings. PMID:16964229

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.

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

Using education on irradiated foods to change behavior of Korean elementary, middle, and high school students

PubMed Central

Kim, Jaerok; Choi, Yoonseok

2014-01-01

BACKGROUND/OBJECTIVES Educational interventions targeted food selection perception, knowledge, attitude, and behavior. Education regarding irradiated food was intended to change food selection behavior specific to it. SUBJECTS AND METHODS There were 43 elementary students (35.0%), 45 middle school students (36.6%), and 35 high school students (28.5%). The first step was research design. Educational targets were selected and informed consent was obtained in step two. An initial survey was conducted as step three. Step four was a 45 minute-long theoretical educational intervention. Step five concluded with a survey and experiment on food selection behavior. RESULTS As a result of conducting a 45 minute-long education on the principles, actual state of usage, and pros and cons of irradiated food for elementary, middle, and high-school students in Korea, perception, knowledge, attitude, and behavior regarding the irradiated food was significantly higher after the education than before the education (P < 0.000). CONCLUSIONS The behavior of irradiated food selection shows high correlation with all variables of perception, knowledge, and attitude, and it is necessary to provide information of each level of change in perception, knowledge, and attitude in order to derive proper behavior change, which is the ultimate goal of the education. PMID:25324942

Influence of the Selectivity Filter Properties on Proton Selectivity in the Influenza A M2 Channel.

PubMed

Dudev, Todor; Grauffel, Cédric; Lim, Carmay

2016-10-05

The homotetrameric M2 proton channel of influenza A plays a crucial role in the viral life cycle and is thus an important therapeutic target. It selectively conducts protons against a background of other competing cations whose concentrations are up to a million times greater than the proton concentration. Its selectivity is largely determined by a constricted region of its open pore known as the selectivity filter, which is lined by four absolutely conserved histidines. While the mechanism of proton transport through the channel has been studied, the physical principles underlying the selectivity for protons over other cations in the channel's His 4 selectivity filter remain elusive. Furthermore, it is not known if proton selectivity absolutely requires all four histidines with two of the four histidines protonated and if other titratable amino acid residues in lieu of the histidines could bind protons and how they affect proton selectivity. Here, we elucidate how the competition between protons and rival cations such as Na + depends on the selectivity filter's (1) histidine protonation state, (2) solvent exposure, (3) oligomeric state (the number of protein chains and thus the number of His ligands), and (4) ligand composition by evaluating the free energies for replacing monovalent Na + with H 3 O + in various model selectivity filters. We show that tetrameric His 4 filters are more proton-selective than their trimeric His 3 counterparts, and a dicationic His 4 filter where two of the four histidines are protonated is more proton-selective than tetrameric filters with other charge states/composition (different combinations of His protonation states or different metal-ligating ligands). The [His 4 ] 2+ filter achieves proton selectivity by providing suboptimal binding conditions for rival cations such as Na + , which prefers a neutral or negatively charged filter instead of a dicationic one, and three rather than four ligands with oxygen-ligating atoms.

Absolute determination of single-stranded and self-complementary adeno-associated viral vector genome titers by droplet digital PCR.

PubMed

Lock, Martin; Alvira, Mauricio R; Chen, Shu-Jen; Wilson, James M

2014-04-01

Accurate titration of adeno-associated viral (AAV) vector genome copies is critical for ensuring correct and reproducible dosing in both preclinical and clinical settings. Quantitative PCR (qPCR) is the current method of choice for titrating AAV genomes because of the simplicity, accuracy, and robustness of the assay. However, issues with qPCR-based determination of self-complementary AAV vector genome titers, due to primer-probe exclusion through genome self-annealing or through packaging of prematurely terminated defective interfering (DI) genomes, have been reported. Alternative qPCR, gel-based, or Southern blotting titering methods have been designed to overcome these issues but may represent a backward step from standard qPCR methods in terms of simplicity, robustness, and precision. Droplet digital PCR (ddPCR) is a new PCR technique that directly quantifies DNA copies with an unparalleled degree of precision and without the need for a standard curve or for a high degree of amplification efficiency; all properties that lend themselves to the accurate quantification of both single-stranded and self-complementary AAV genomes. Here we compare a ddPCR-based AAV genome titer assay with a standard and an optimized qPCR assay for the titration of both single-stranded and self-complementary AAV genomes. We demonstrate absolute quantification of single-stranded AAV vector genomes by ddPCR with up to 4-fold increases in titer over a standard qPCR titration but with equivalent readout to an optimized qPCR assay. In the case of self-complementary vectors, ddPCR titers were on average 5-, 1.9-, and 2.3-fold higher than those determined by standard qPCR, optimized qPCR, and agarose gel assays, respectively. Droplet digital PCR-based genome titering was superior to qPCR in terms of both intra- and interassay precision and is more resistant to PCR inhibitors, a desirable feature for in-process monitoring of early-stage vector production and for vector genome biodistribution analysis in inhibitory tissues.

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.

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.

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.

Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer's disease: a prospective, open-label pilot study.

PubMed

Ohnuma, Tohru; Toda, Aiko; Kimoto, Ayako; Takebayashi, Yuto; Higashiyama, Ryoko; Tagata, Yuko; Ito, Masanobu; Ota, Tsuneyoshi; Shibata, Nobuto; Arai, Heii

2016-01-01

This is the first clinical trial of this type in Japan, designed to analyze two important aspects of Alzheimer's disease (AD) management using medium-chain triglycerides. Axona was administered for 3 months (40 g of powder containing 20 g of caprylic triglycerides). We used an indurating, four-step dose-titration method (from 10 to 40 g per day) for 7 days before the trial, and examined the tolerance and adverse effects of this intervention. We also investigated its effect on cognitive function in mild-to-moderate AD patients. This was a clinical intervention in 22 Japanese patients with sporadic AD at a mild-to-moderate stage (ten females, 12 males), mean age (± standard deviation) 63.9 (±8.5) years, Mini-Mental State Examination (MMSE) score, 10-25, seven patients were ApoE4-positive. During Axona administration, we examined changes in cognitive function by obtaining MMSE and AD assessment-scale scores. Intolerance and serum ketone concentrations were also examined. The tolerance of Axona was good, without severe gastrointestinal adverse effects. Axona did not improve cognitive function in our sample of AD patients, even in those patients without the ApoE4 allele. However, some ApoE4-negative patients with baseline MMSE score ≥14 showed improvement in their cognitive functions. The modified dose-titration method, starting with a low dose of Axona, decreased gastrointestinal adverse effects in Japanese patients. Axona might be effective for some relatively mildly affected patients with AD (with cognitive function MMSE score of ≥14 and lacking the ApoE4 allele).

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.

Determination of vanadium(V) by direct automatic potentiometric titration with EDTA using a chemically modified electrode as a potentiometric sensor.

PubMed

Quintar, S E; Santagata, J P; Cortinez, V A

2005-10-15

A chemically modified electrode (CME) was prepared and studied as a potentiometric sensor for the end-point detection in the automatic titration of vanadium(V) with EDTA. The CME was constructed with a paste prepared by mixing spectral-grade graphite powder, Nujol oil and N-2-naphthoyl-N-p-tolylhydroxamic acid (NTHA). Buffer systems, pH effects and the concentration range were studied. Interference ions were separated by applying a liquid-liquid extraction procedure. The CME did not require any special conditioning before using. The electrode was constructed with very inexpensive materials and was easily made. It could be continuously used, at least two months without removing the paste. Automatic potentiometric titration curves were obtained for V(V) within 5 x 10(-5) to 2 x 10(-3)M with acceptable accuracy and precision. The developed method was applied to V(V) determination in alloys for hip prosthesis.

Systemic errors in quantitative polymerase chain reaction titration of self-complementary adeno-associated viral vectors and improved alternative methods.

PubMed

Fagone, Paolo; Wright, J Fraser; Nathwani, Amit C; Nienhuis, Arthur W; Davidoff, Andrew M; Gray, John T

2012-02-01

Self-complementary AAV (scAAV) vector genomes contain a covalently closed hairpin derived from a mutated inverted terminal repeat that connects the two monomer single-stranded genomes into a head-to-head or tail-to-tail dimer. We found that during quantitative PCR (qPCR) this structure inhibits the amplification of proximal amplicons and causes the systemic underreporting of copy number by as much as 10-fold. We show that cleavage of scAAV vector genomes with restriction endonuclease to liberate amplicons from the covalently closed terminal hairpin restores quantitative amplification, and we implement this procedure in a simple, modified qPCR titration method for scAAV vectors. In addition, we developed and present an AAV genome titration procedure based on gel electrophoresis that requires minimal sample processing and has low interassay variability, and as such is well suited for the rigorous quality control demands of clinical vector production facilities.

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.

Effect of two-step and one-step surface conditioning of glass ceramic on adhesion strength of orthodontic bracket and effect of thermo-cycling on adhesion strength.

PubMed

Asiry, Moshabab A; AlShahrani, Ibrahim; Alaqeel, Samer M; Durgesh, Bangalore H; Ramakrishnaiah, Ravikumar

2018-08-01

The adhesion strength of orthodontic brackets bonded to dental glass ceramics was evaluated after ceramic surface was treated with two-step and one-step surface conditioning systems, and subjecting to thermo-cycling. A total of forty specimens were fabricated from silica based glass ceramic (lithium disilicate) by duplicating the buccal surface of maxillary first premolar. The specimens were randomly assigned to two experimental groups (n = 20), group one specimens were treated with two-step surface conditioning system (IPS ceramic etching gel™ and Monobond plus™) and group two specimens were treated with one-step surface conditioning system (Monobond etch and prime™). The surface roughness of the specimens after treatment with two-step and one-step surface conditioning system was measured using non-contact surface profilometer. Ten randomly selected specimens from each group were subjected to thermo-cycling and the remaining ten served as baseline. The shear bond strength of the specimens was measured using universal material testing machine. The adhesive remnant index score was calculated, and the results of surface roughness and bond strength were tabulated and subjected to analysis of variance and post hoc tukey's test at a significance level of p < 0.05. The results of the study showed that the specimens treated with two-step conditioning system had higher surface roughness and bond strength than one-step conditioning system. The majority of the specimens treated with both two-step and one-step conditioned specimens showed adhesive failure after subjecting thermo-cycling. Traditional two-step conditioning provides better bond strength. The clinical importance of the study is that, the silane promoted adhesion significantly reduces on exposure to thermo-cycling. Copyright © 2018 Elsevier Ltd. All rights reserved.

Accuracy, Precision, Ease-Of-Use, and Cost of Methods to Test Ebola-Relevant Chlorine Solutions

PubMed Central

Wells, Emma; Wolfe, Marlene K.; Murray, Anna; Lantagne, Daniele

2016-01-01

To prevent transmission in Ebola Virus Disease (EVD) outbreaks, it is recommended to disinfect living things (hands and people) with 0.05% chlorine solution and non-living things (surfaces, personal protective equipment, dead bodies) with 0.5% chlorine solution. In the current West African EVD outbreak, these solutions (manufactured from calcium hypochlorite (HTH), sodium dichloroisocyanurate (NaDCC), and sodium hypochlorite (NaOCl)) have been widely used in both Ebola Treatment Unit and community settings. To ensure solution quality, testing is necessary, however test method appropriateness for these Ebola-relevant concentrations has not previously been evaluated. We identified fourteen commercially-available methods to test Ebola-relevant chlorine solution concentrations, including two titration methods, four DPD dilution methods, and six test strips. We assessed these methods by: 1) determining accuracy and precision by measuring in quintuplicate five different 0.05% and 0.5% chlorine solutions manufactured from NaDCC, HTH, and NaOCl; 2) conducting volunteer testing to assess ease-of-use; and, 3) determining costs. Accuracy was greatest in titration methods (reference-12.4% error compared to reference method), then DPD dilution methods (2.4–19% error), then test strips (5.2–48% error); precision followed this same trend. Two methods had an accuracy of <10% error across all five chlorine solutions with good precision: Hach digital titration for 0.05% and 0.5% solutions (recommended for contexts with trained personnel and financial resources), and Serim test strips for 0.05% solutions (recommended for contexts where rapid, inexpensive, and low-training burden testing is needed). Measurement error from test methods not including pH adjustment varied significantly across the five chlorine solutions, which had pH values 5–11. Volunteers found test strip easiest and titration hardest; costs per 100 tests were $14–37 for test strips and $33–609 for titration. Given the ease-of-use and cost benefits of test strips, we recommend further development of test strips robust to pH variation and appropriate for Ebola-relevant chlorine solution concentrations. PMID:27243817

8-Hydroxyquinoline based push-pull azo dye: Novel colorimetric chemosensor for anion detection

NASA Astrophysics Data System (ADS)

Arslan, Ömer; Aydıner, Burcu; Yalçın, Ergin; Babür, Banu; Seferoğlu, Nurgül; Seferoğlu, Zeynel

2017-12-01

A novel colorimetric chemosensor based on push-pull dye (8HQA) was synthesized and characterized by using IR, 1H/13C NMR and HRMS for the purpose of recognition of anions and cations in DMSO. The absorption maxima of the chemosensor were determined in different solvents. The selectivity and sensitivity of 8HQA to anions were determined with spectrophotometric and 1H NMR titration techniques. The selectivity of 8HQA for studied anions (CN-, F-, Cl-, I-, AcO-, HSO4- and H2PO4-) was determined in DMSO. There is no selectivity between competing anions such as CN-, F- AcO- and H2PO4- at the stoichiometric ratio of 1:1 in UV-vis titrations experiments however, it was observed different color changes upon addition of CN-, F-, AcO- and H2PO4- to the DMSO solution. In addition, the chemosensor showed no colorimetric response for the following anions; Cl-, I- and HSO4- in DMSO. The colorimetric sensing ability of 8HQA was studied in the presence of chloride salts of different cations such as Ca2+, Mg2+, Cu2+, Co2+, Sn2+, Ni2+, Cd2+ and Hg2+. Upon the addition of 4 equiv of each of the cations showed bathochromic shifts except for Ca2+and Cu2+. Interestingly, no selectivity was observed in interaction with metal cations. In addition, the molecular and electronic structures of 8HQA, as well as the molecular complexes of 8HQA, formed with the anions, were obtained theoretically and confirmed by DFT and TD-DFT calculations.

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.

Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two-step triage protocol.

PubMed

Van Calster, B; Bobdiwala, S; Guha, S; Van Hoorde, K; Al-Memar, M; Harvey, R; Farren, J; Kirk, E; Condous, G; Sur, S; Stalder, C; Timmerman, D; Bourne, T

2016-11-01

A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step triage protocol to select PUL at high risk of ectopic pregnancy (EP), based on serum progesterone level at presentation (step 1) and the serum human chorionic gonadotropin (hCG) ratio, defined as the ratio of hCG at 48 h to hCG at presentation (step 2). This was a cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL data from two London-based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to assign PUL as low risk with high confidence (high negative predictive value (NPV)) while classifying most EP as high risk (high sensitivity). The first triage step assigned PUL as low risk using a threshold of serum progesterone at presentation. The remaining PUL were triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low risk as an estimated EP risk of < 5%. On validation, initial serum progesterone ≤ 2 nmol/L (step 1) classified 16.1% PUL as low risk. Second-step classification with the risk model selected an additional 46.0% of all PUL as low risk. Overall, the two-step protocol classified 62.1% of PUL as low risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low risk with 99.1% NPV and 94.9% sensitivity. PUL can be classified efficiently into being either high or low risk for complications using a two-step protocol involving initial progesterone and hCG levels and the hCG ratio. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Standard Free Droplet Digital Polymerase Chain Reaction as a New Tool for the Quality Control of High-Capacity Adenoviral Vectors in Small-Scale Preparations

PubMed Central

Boehme, Philip; Stellberger, Thorsten; Solanki, Manish; Zhang, Wenli; Schulz, Eric; Bergmann, Thorsten; Liu, Jing; Doerner, Johannes; Baiker, Armin E.

2015-01-01

Abstract High-capacity adenoviral vectors (HCAdVs) are promising tools for gene therapy as well as for genetic engineering. However, one limitation of the HCAdV vector system is the complex, time-consuming, and labor-intensive production process and the following quality control procedure. Since HCAdVs are deleted for all viral coding sequences, a helper virus (HV) is needed in the production process to provide the sequences for all viral proteins in trans. For the purification procedure of HCAdV, cesium chloride density gradient centrifugation is usually performed followed by buffer exchange using dialysis or comparable methods. However, performing these steps is technically difficult, potentially error-prone, and not scalable. Here, we establish a new protocol for small-scale production of HCAdV based on commercially available adenovirus purification systems and a standard method for the quality control of final HCAdV preparations. For titration of final vector preparations, we established a droplet digital polymerase chain reaction (ddPCR) that uses a standard free-end-point PCR in small droplets of defined volume. By using different probes, this method is capable of detecting and quantifying HCAdV and HV in one reaction independent of reference material, rendering this method attractive for accurately comparing viral titers between different laboratories. In summary, we demonstrate that it is possible to produce HCAdV in a small scale of sufficient quality and quantity to perform experiments in cell culture, and we established a reliable protocol for vector titration based on ddPCR. Our method significantly reduces time and required equipment to perform HCAdV production. In the future the ddPCR technology could be advantageous for titration of other viral vectors commonly used in gene therapy. PMID:25640117

Comparison of methods for acid quantification: impact of resist components on acid-generating efficiency

NASA Astrophysics Data System (ADS)

Cameron, James F.; Fradkin, Leslie; Moore, Kathryn; Pohlers, Gerd

2000-06-01

Chemically amplified deep UV (CA-DUV) positive resists are the enabling materials for manufacture of devices at and below 0.18 micrometer design rules in the semiconductor industry. CA-DUV resists are typically based on a combination of an acid labile polymer and a photoacid generator (PAG). Upon UV exposure, a catalytic amount of a strong Bronsted acid is released and is subsequently used in a post-exposure bake step to deprotect the acid labile polymer. Deprotection transforms the acid labile polymer into a base soluble polymer and ultimately enables positive tone image development in dilute aqueous base. As CA-DUV resist systems continue to mature and are used in increasingly demanding situations, it is critical to develop a fundamental understanding of how robust these materials are. One of the most important factors to quantify is how much acid is photogenerated in these systems at key exposure doses. For the purpose of quantifying photoacid generation several methods have been devised. These include spectrophotometric methods, ion conductivity methods and most recently an acid-base type titration similar to the standard addition method. This paper compares many of these techniques. First, comparisons between the most commonly used acid sensitive dye, tetrabromophenol blue sodium salt (TBPB) and a less common acid sensitive dye, Rhodamine B base (RB) are made in several resist systems. Second, the novel acid-base type titration based on the standard addition method is compared to the spectrophotometric titration method. During these studies, the make up of the resist system is probed as follows: the photoacid generator and resist additives are varied to understand the impact of each of these resist components on the acid generation process.

Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking

PubMed Central

Ross, Kathryn C.; Gubner, Noah R.; Tyndale, Rachel F.; Hawk, Larry W.; Lerman, Caryn; George, Tony P.; Cinciripini, Paul; Schnoll, Robert A.; Benowitz, Neal L.

2016-01-01

Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity. Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers. There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites. The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure. Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed. The results indicated that rate of nicotine metabolism is a more important factor influencing nicotine intake in White smokers. Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine. However, this relationship was not found in African Americans. Overall there was a greater step down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers. PMID:27180107

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

Integration and global analysis of isothermal titration calorimetry data for studying macromolecular interactions.

PubMed

Brautigam, Chad A; Zhao, Huaying; Vargas, Carolyn; Keller, Sandro; Schuck, Peter

2016-05-01

Isothermal titration calorimetry (ITC) is a powerful and widely used method to measure the energetics of macromolecular interactions by recording a thermogram of differential heating power during a titration. However, traditional ITC analysis is limited by stochastic thermogram noise and by the limited information content of a single titration experiment. Here we present a protocol for bias-free thermogram integration based on automated shape analysis of the injection peaks, followed by combination of isotherms from different calorimetric titration experiments into a global analysis, statistical analysis of binding parameters and graphical presentation of the results. This is performed using the integrated public-domain software packages NITPIC, SEDPHAT and GUSSI. The recently developed low-noise thermogram integration approach and global analysis allow for more precise parameter estimates and more reliable quantification of multisite and multicomponent cooperative and competitive interactions. Titration experiments typically take 1-2.5 h each, and global analysis usually takes 10-20 min.

Index Fund Selections with GAs and Classifications Based on Turnover

NASA Astrophysics Data System (ADS)

Orito, Yukiko; Motoyama, Takaaki; Yamazaki, Genji

It is well known that index fund selections are important for the risk hedge of investment in a stock market. The`selection’means that for`stock index futures’, n companies of all ones in the market are selected. For index fund selections, Orito et al.(6) proposed a method consisting of the following two steps : Step 1 is to select N companies in the market with a heuristic rule based on the coefficient of determination between the return rate of each company in the market and the increasing rate of the stock price index. Step 2 is to construct a group of n companies by applying genetic algorithms to the set of N companies. We note that the rule of Step 1 is not unique. The accuracy of the results using their method depends on the length of time data (price data) in the experiments. The main purpose of this paper is to introduce a more`effective rule’for Step 1. The rule is based on turnover. The method consisting of Step 1 based on turnover and Step 2 is examined with numerical experiments for the 1st Section of Tokyo Stock Exchange. The results show that with our method, it is possible to construct the more effective index fund than the results of Orito et al.(6). The accuracy of the results using our method depends little on the length of time data (turnover data). The method especially works well when the increasing rate of the stock price index over a period can be viewed as a linear time series data.

Adsorption process to recover hydrogen from feed gas mixtures having low hydrogen concentration

DOEpatents

Golden, Timothy Christopher; Weist, Jr., Edward Landis; Hufton, Jeffrey Raymond; Novosat, Paul Anthony

2010-04-13

A process for selectively separating hydrogen from at least one more strongly adsorbable component in a plurality of adsorption beds to produce a hydrogen-rich product gas from a low hydrogen concentration feed with a high recovery rate. Each of the plurality of adsorption beds subjected to a repetitive cycle. The process comprises an adsorption step for producing the hydrogen-rich product from a feed gas mixture comprising 5% to 50% hydrogen, at least two pressure equalization by void space gas withdrawal steps, a provide purge step resulting in a first pressure decrease, a blowdown step resulting in a second pressure decrease, a purge step, at least two pressure equalization by void space gas introduction steps, and a repressurization step. The second pressure decrease is at least 2 times greater than the first pressure decrease.

Multi-site binding of epigallocatechin gallate to human serum albumin measured by NMR and isothermal titration calorimetry

PubMed Central

Eaton, Joshua D.

2017-01-01

The affinity of epigallocatechin gallate (EGCG) for human serum albumin (HSA) was measured in physiological conditions using NMR and isothermal titration calorimetry (ITC). NMR estimated the Ka (self-dissociation constant) of EGCG as 50 mM. NMR showed two binding events: strong (n1=1.8 ± 0.2; Kd1 =19 ± 12 μM) and weak (n2∼20; Kd2 =40 ± 20 mM). ITC also showed two binding events: strong (n1=2.5 ± 0.03; Kd1 =21.6 ± 4.0 μM) and weak (n2=9 ± 1; Kd2 =22 ± 4 mM). The two techniques are consistent, with an unexpectedly high number of bound EGCG. The strong binding is consistent with binding in the two Sudlow pockets. These results imply that almost all EGCG is transported in the blood bound to albumin and explains the wide tissue distribution and chemical stability of EGCG in vivo. PMID:28424370

Measurement of Nanomolar Dissociation Constants by Titration Calorimetry and Thermal Shift Assay – Radicicol Binding to Hsp90 and Ethoxzolamide Binding to CAII

PubMed Central

Zubrienė, Asta; Matulienė, Jurgita; Baranauskienė, Lina; Jachno, Jelena; Torresan, Jolanta; Michailovienė, Vilma; Cimmperman, Piotras; Matulis, Daumantas

2009-01-01

The analysis of tight protein-ligand binding reactions by isothermal titration calorimetry (ITC) and thermal shift assay (TSA) is presented. The binding of radicicol to the N-terminal domain of human heat shock protein 90 (Hsp90αN) and the binding of ethoxzolamide to human carbonic anhydrase (hCAII) were too strong to be measured accurately by direct ITC titration and therefore were measured by displacement ITC and by observing the temperature-denaturation transitions of ligand-free and ligand-bound protein. Stabilization of both proteins by their ligands was profound, increasing the melting temperature by more than 10 ºC, depending on ligand concentration. Analysis of the melting temperature dependence on the protein and ligand concentrations yielded dissociation constants equal to 1 nM and 2 nM for Hsp90αN-radicicol and hCAII-ethoxzolamide, respectively. The ligand-free and ligand-bound protein fractions melt separately, and two melting transitions are observed. This phenomenon is especially pronounced when the ligand concentration is equal to about half the protein concentration. The analysis compares ITC and TSA data, accounts for two transitions and yields the ligand binding constant and the parameters of protein stability, including the Gibbs free energy and the enthalpy of unfolding. PMID:19582223

Electrohydrodynamic properties of succinoglycan as probed by fluorescence correlation spectroscopy, potentiometric titration and capillary electrophoresis.

PubMed

Duval, Jérôme F L; Slaveykova, Vera I; Hosse, Monika; Buffle, Jacques; Wilkinson, Kevin J

2006-10-01

The electrostatic, hydrodynamic and conformational properties of aqueous solutions of succinoglycan have been analyzed by fluorescence correlation spectroscopy (FCS), proton titration, and capillary electrophoresis (CE) over a large range of pH values and electrolyte (NaCl) concentrations. Using the theoretical formalism developed previously for the electrokinetic properties of soft, permeable particles, a quantitative analysis for the electro-hydrodynamics of succinoglycan is performed by taking into account, in a self-consistent manner, the measured values of the diffusion coefficients, electric charge densities, and electrophoretic mobilities. For that purpose, two limiting conformations for the polysaccharide in solution are tested, i.e. succinoglycan behaves as (i) a spherical, random coil polymer or (ii) a rodlike particle with charged lateral chains. The results show that satisfactory modeling of the titration data for ionic strengths larger than 50 mM can be accomplished using both geometries over the entire range of pH values. Electrophoretic mobilities measured for sufficiently large pH values (pH > 5-6) are in line with predictions based on either model. The best manner to discriminate between these two conceptual models is briefly discussed. For low pH values (pH < 5), both models indicate aggregation, resulting in an increase of the hydrodynamic permeability and a decrease of the diffusion coefficient.

Effects of system net charge and electrostatic truncation on all-atom constant pH molecular dynamics †

PubMed Central

Chen, Wei; Shen, Jana K.

2014-01-01

Constant pH molecular dynamics offers a means to rigorously study the effects of solution pH on dynamical processes. Here we address two critical questions arising from the most recent developments of the all-atom continuous constant pH molecular dynamics (CpHMD) method: 1) What is the effect of spatial electrostatic truncation on the sampling of protonation states? 2) Is the enforcement of electrical neutrality necessary for constant pH simulations? We first examined how the generalized reaction field and force shifting schemes modify the electrostatic forces on the titration coordinates. Free energy simulations of model compounds were then carried out to delineate the errors in the deprotonation free energy and salt-bridge stability due to electrostatic truncation and system net charge. Finally, CpHMD titration of a mini-protein HP36 was used to understand the manifestation of the two types of errors in the calculated pK a values. The major finding is that enforcing charge neutrality under all pH conditions and at all time via co-titrating ions significantly improves the accuracy of protonation-state sampling. We suggest that such finding is also relevant for simulations with particle-mesh Ewald, considering the known artifacts due to charge-compensating background plasma. PMID:25142416

Nonlinear Analyte Concentration Gradients for One-Step Kinetic Analysis Employing Optical Microring Resonators

PubMed Central

Marty, Michael T.; Kuhnline Sloan, Courtney D.; Bailey, Ryan C.; Sligar, Stephen G.

2012-01-01

Conventional methods to probe the binding kinetics of macromolecules at biosensor surfaces employ a stepwise titration of analyte concentrations and measure the association and dissociation to the immobilized ligand at each concentration level. It has previously been shown that kinetic rates can be measured in a single step by monitoring binding as the analyte concentration increases over time in a linear gradient. We report here the application of nonlinear analyte concentration gradients for determining kinetic rates and equilibrium binding affinities in a single experiment. A versatile nonlinear gradient maker is presented, which is easily applied to microfluidic systems. Simulations validate that accurate kinetic rates can be extracted for a wide range of association and dissociation rates, gradient slopes and curvatures, and with models for mass transport. The nonlinear analyte gradient method is demonstrated with a silicon photonic microring resonator platform to measure prostate specific antigen-antibody binding kinetics. PMID:22686186

Synthesis of a thiol-β-cyclodextrin, a potential agent for controlling enzymatic browning in fruits and vegetables.

PubMed

Manta, Carmen; Peralta-Altier, Gabriela; Gioia, Larissa; Méndez, María F; Seoane, Gustavo; Ovsejevi, Karen

2013-11-27

A thiol-β-cyclodextrin was synthesized by a simple and environmentally friendly three-step method comprising epoxy activation of β-cyclodextrin, thiosulfate-mediated oxirane opening, and further reduction of the S-alkyl thiosulfate to a thiol group. The final step was optimized by using thiopropyl-agarose, a solid phase reducing agent with many advantages over soluble ones. β-Cyclodextrin thiolation was confirmed by titration with a thiol-reactive reagent, NMR studies, and MALDI-TOF/TOF. Thiolated cyclodextrin had an average value of one thiol group per molecule. Thiol-β-cyclodextrin proved to be an excellent agent for controlling polyphenol oxidase activity. This copper-containing enzyme is responsible for browning in fruits and vegetables. Under the same conditions, thiol-β-cyclodextrin generated a reductive microenvironment that increased the antibrowning effect on Red Delicious apples compared to unmodified β-cyclodextrin.

Nonlinear analyte concentration gradients for one-step kinetic analysis employing optical microring resonators.

PubMed

Marty, Michael T; Sloan, Courtney D Kuhnline; Bailey, Ryan C; Sligar, Stephen G

2012-07-03

Conventional methods to probe the binding kinetics of macromolecules at biosensor surfaces employ a stepwise titration of analyte concentrations and measure the association and dissociation to the immobilized ligand at each concentration level. It has previously been shown that kinetic rates can be measured in a single step by monitoring binding as the analyte concentration increases over time in a linear gradient. We report here the application of nonlinear analyte concentration gradients for determining kinetic rates and equilibrium binding affinities in a single experiment. A versatile nonlinear gradient maker is presented, which is easily applied to microfluidic systems. Simulations validate that accurate kinetic rates can be extracted for a wide range of association and dissociation rates, gradient slopes, and curvatures, and with models for mass transport. The nonlinear analyte gradient method is demonstrated with a silicon photonic microring resonator platform to measure prostate specific antigen-antibody binding kinetics.

Gas Separation Using Organic-Vapor-Resistent Membranes In Conjunctin With Organic-Vapor-Selective Membranes

DOEpatents

Baker, Richard W.; Pinnau, Ingo; He, Zhenjie; Da Costa, Andre R.; Daniels, Ramin; Amo, Karl D.; Wijmans, Johannes G.

2003-06-03

A process for treating a gas mixture containing at least an organic compound gas or vapor and a second gas, such as natural gas, refinery off-gas or air. The process uses two sequential membrane separation steps, one using membrane selective for the organic compound over the second gas, the other selective for the second gas over the organic vapor. The second-gas-selective membranes use a selective layer made from a polymer having repeating units of a fluorinated polymer, and demonstrate good resistance to plasticization by the organic components in the gas mixture under treatment, and good recovery after exposure to liquid aromatic hydrocarbons. The membrane steps can be combined in either order.

Potentiometric titration of polyhexamethylene biguanide hydrochloride with potassium poly(vinyl sulfate) solution using a cationic surfactant-selective electrode.

PubMed

Masadome, Takashi; Yamagishi, Yuichi; Takano, Masaki; Hattori, Toshiaki

2008-03-01

A potentiometric titration method using a cationic surfactant as an indicator cation and a plasticized poly(vinyl chloride) membrane electrode sensitive to the cationic surfactant is proposed for the determination of polyhexamethylene biguanide hydrochloride (PHMB-HCl), which is a cationic polyelectrolyte. A sample solution of PHMB-HCl containing an indicator cation (hexadecyltrimethylammonium ion, HTA) was titrated with a standard solution of an anionic polyelectrolyte, potassium poly(vinyl sulfate) (PVSK). The end-point was detected as a sharp potential change due to an abrupt decrease in the concentration of the indicator cation, HTA, which is caused by its association with PVSK. The effects of the concentrations of HTA ion and coexisting electrolytes in the sample solution on the degree of the potential change at the end-point were examined. A linear relationship between the concentration of PHMB-HCl and the end-point volume of the titrant exists in the concentration range from 2.0 x 10(-5) to 4.0 x 10(-4) M in the case that the concentration of HTA is 1.0 x 10(-5) M, and that from 1.0 x 10(-6) to 1.2 x 10(-5) M in the case that the concentration of HTA is 5.0 x 10(-6) M, respectively. The proposed method was applied to the determination of PHMB-HCl in some contact-lens detergents.

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.

[Treatment of pain with peridural administration of opioids].

PubMed

Chrubasik, S; Senninger, N; Chrubasik, J

1996-07-01

The advantages and disadvantages associated with epidural opioids require careful selection of the opioid and its dosage. There is presently no ideal opioid available for epidural use. Comparative pharmacokinetic data help to select the appropriate epidural opioid. Morphine (provided it is given in small doses and volumes) is very appropriate for epidural pain treatment, especially for longer periods of treatment, due to excellent analgesia and very low systemic morphine concentrations. The faster onset of analgesia with epidural pethidine, alfentanil und fentanyl make these opioids recommendable. However, due to the increased risk of respiratory depression during continuous treatment, these drugs should not be given over extended periods. Epidural administration of methadone, sufentanil und buprenorphine cannot be recommended since the advantages over systemic use do not outweigh the risks. Epidural tramadol may be useful in clinical routine, if opioids are not available and supervision of the patient is not guaranteed, because tramadol is not restricted by law and has a low potential for central depressive effects. The safety of the patients should be paramount. If patients are harmed by inappropriate opioids or dose regimens this will discredit a valuable for treating postoperative pain. Postoperative epidural dosages should be as low as possible and be titrated to the patient's individual needs for analgesia. Epidural morphine treatment is an alternative to step 4 of the WHO treatment regimen for patients with intractable pain or those suffering from systemic opioid side effects. Careful selection of patients helps to increase successful treatment. If implantable devices (ports or pumps, according to the life expectancy) are employed, the intrathecal route of administration is preferable to the epidural route, as the latter has a 10 times higher morphine dose requirement.

Structural Reorganization and the Cooperative Binding of Single-stranded Telomere DNA in Sterkiella nova*

PubMed Central

Buczek, Pawel; Horvath, Martin P.

2009-01-01

In Sterkiella nova, α and β telomere proteins bind cooperatively with single-stranded DNA to form a ternary α·β·DNA complex. Association of telomere protein subunits is DNA-dependent, and α-β association enhances DNA affinity. To further understand the molecular basis for binding cooperativity, we characterized several possible stepwise assembly pathways using isothermal titration calorimetry. In one path, α and DNA first form a stable α·DNA complex followed by addition of β in a second step. Binding energy accumulates with nearly equal free energy of association for each of these steps. Heat capacity is nonetheless dramatically different with ΔCp = −305 ± 3 cal mol−1 K−1 for α binding with DNA and ΔCp = −2010 ± 20 cal mol−1 K−1 for addition of β to complete the α·β·DNA complex. By examining alternate routes including titration of single-stranded DNA with a preformed α·β complex, a significant portion of binding energy and heat capacity could be assigned to structural reorganization involving protein-protein interactions and repositioning of the DNA. Structural reorganization probably affords a mechanism to regulate high affinity binding of telomere single-stranded DNA with important implications for telomere biology. Regulation of telomere complex dissociation is thought to involve post-translational modifications in the lysine-rich C-terminal portion of β. We observed no difference in binding energetics or crystal structure when comparing complexes prepared with full-length β or a C-terminally truncated form, supporting interesting parallels between the intrinsically disordered regions of histones and this portion of β. PMID:17082188

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.

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

Novel aminobenzanthrone dyes for amyloid fibril detection

NASA Astrophysics Data System (ADS)

Vus, Kateryna; Trusova, Valeriya; Gorbenko, Galyna; Kirilova, Elena; Kirilov, Georgiy; Kalnina, Inta; Kinnunen, Paavo

2012-04-01

A series of novel fluorescent aminobenzanthrone dyes have been tested for their ability to identify and characterize the oligomeric and fibrillar aggregates of lysozyme. The parameters of the dye binding to native, oligomeric and fibrillar protein have been calculated from the results of fluorimetric titration. Furthermore, several additional quantities reflecting the preference of the probe to either pre-fibrillar or fibrillar protein aggregates, have been evaluated. Based on the comparative analysis of the recovered parameters, AM4 was recommended for selective detection of protein pre-fibrillar assemblies, while the dyes AM1, AM2, AM3 were selected as the most prospective amyloid tracers.

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.

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.

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.

Immobilization of Chlorosulfonyl-Calix[4]arene onto the surface of silica gel through the directly estrification

NASA Astrophysics Data System (ADS)

Taghvaei-Ganjali, Saeed; Zadmard, Reza; Saber-Tehrani, Mandana

2012-06-01

For the first time Chlorosulfonyl-Calix[4]arene has been chemically bonded to silica gel through the directly estrification without silane coupling agent to prepare Chlorosulfonyl-Calix[4]arene-bonded silica gel. Sample characterization was performed by various techniques such as elemental analysis, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDAX), powder X-ray diffraction (XRD), N2 adsorption-desorption, thermal gravimetric analysis (TGA), 29Si CP/MAS spectroscopy and acid-base titration. All data approve the successful incorporation of organic group via covalent bond. From the comparison between sulfur content determined by elemental analysis and the number of H+ determined by acid-base titration, it was shown that two ester units took place onto the new synthesized sample and two acidic sites exist on the surface.

Spectrophotometric Titration of a Mixture of Calcium and Magnesium.

ERIC Educational Resources Information Center

Fulton, Robert; And Others

1986-01-01

Describes a spectrophotometric titration experiment which uses a manual titration spectrophotometer and manually operated buret, rather than special instrumentation. Identifies the equipment, materials, and procedures needed for the completion of the experiment. Recommends the use of this experiment in introductory quantitative analysis…

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

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.

A Microscale Spectrophotometric Determination of Water Hardness

NASA Astrophysics Data System (ADS)

Gordon, James S.

2001-08-01

A spectrophotometric titration was performed to determine water hardness. The titration incorporated the traditional titration method employing EDTA as the titrant and calmagite as the indicator. The microscale experiment was carried out in a spectrometer cuvette and made use of a Texas Instruments (TI-83) calculator interfaced through a TI Calculator-Based Laboratory system to a Vernier colorimeter as the detector. Monitoring at 635 nm, one of the colorimeter's fixed wavelengths, was well suited for this analysis. Agreement was found with results from traditional titrations.

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

The accuracy of autotitrating CPAP-determined residual apnea-hypopnea index.

PubMed

Cilli, Aykut; Uzun, Rusen; Bilge, Ugur

2013-03-01

Autotitrating continuous positive airway pressure (auto-CPAP) devices not only titrate CPAP pressures but also measure residual respiratory events. The aim of the present study was to determine the accuracy of auto-CPAP-derived residual apnea-hypopnea index (AHI). We studied 137 consecutive patients (72.3% men) with obstructive sleep apnea from January 2008 to December 2010 who underwent in-laboratory overnight polysomnography (PSG) using auto-CPAP. We excluded patients with comorbidities like congestive heart disease, chronic obstructive pulmonary disease, or hypoventilation syndromes and patients with central sleep apnea. Residual AHI obtained from the auto-CPAP device by smart card (CPAP-AHI) was compared simultaneously with AHI from an overnight PSG on auto-CPAP (PSG-AHI) using Bland-Altman analysis and Wilcoxon signed-rank test. The mean AHI on the diagnostic study was 45.08 ± 1.8. During the titration, auto-CPAP markedly suppressed the respiratory events (PSG-AHI, 3.40 ± 0.20). On the other hand, CPAP-AHI was 3.35 ± 0.17. Bland-Altman analysis showed good agreement between auto-CPAP-AHI and PSG-AHI (AHI mean difference of 0.05, and the limits of agreement for the AHI were from +4.9 to -4.8). Two methods have also been compared with paired samples t test and no statistically significant difference was found (p > 0.05). Auto-CPAP can identify residual respiratory events equivalent to the use of PSG in a selected population.

Initial Crisis Reaction and Poliheuristic Theory

ERIC Educational Resources Information Center

DeRouen, Karl, Jr.; Sprecher, Christopher

2004-01-01

Poliheuristic (PH) theory models foreign policy decisions using a two-stage process. The first step eliminates alternatives on the basis of a simplifying heuristic. The second step involves a selection from among the remaining alternatives and can employ a more rational and compensatory means of processing information. The PH model posits that…

Titanium (III) cation selective electrode based on synthesized tris(2pyridyl) methylamine ionophore and its application in water samples

NASA Astrophysics Data System (ADS)

Rezayi, Majid; Karazhian, Reza; Abdollahi, Yadollah; Narimani, Leila; Sany, Seyedeh Belin Tavakoly; Ahmadzadeh, Saeid; Alias, Yatimah

2014-04-01

The introduction of low detection limit ion selective electrodes (ISEs) may well pave the way for the determination of trace targets of cationic compounds. This research focuses on the detection of titanium (III) cation using a new PVC-membrane sensor based on synthesized tris(2pyridyl) methylamine (tpm) ionophore. The application and validation of the proposed sensor was done using potentiometric titration, inductively coupled plasma atomic emission spectrometry (ICP-AES), and atomic absorption spectrometry (AAS). The membrane sensor exhibited a Nernstian response to the titanium (III) cation over a concentration range of 1.0 × 10-6-1.0 × 10-2 M and pH range from 1-2.5. The Nernstian slope, the lower of detection (LOD), and the response time (t95%) of the proposed sensor were 29.17 +/- 0.24 mV/dec, 7.9 × 10-7 M, and 20 s, respectively. The direct determination of 4-39 μg/ml of titanium (III) standard solution showed an average recovery of 94.60 and a mean relative standard deviation of 1.8 at 100.0 μg/ml. Finally, the utilization of the electrodes as end-point indicators for potentiometric titration with EDTA solutions for titanium (III) sensor was successfully carried out.

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.

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.

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

Analytical electron tomography mapping of the SiCporeoxidation at the nanoscale

NASA Astrophysics Data System (ADS)

Florea, Ileana; Ersen, Ovidiu; Hirlimann, Charles; Roiban, Lucian; Deneuve, Adrien; Houllé, Matthieu; Janowska, Izabela; Nguyen, Patrick; Pham, Charlotte; Pham-Huu, Cuong

2010-12-01

Silicon carbide is a ceramic material that has been widely studied because of its potential applications, ranging from electronics to heterogeneous catalysis. Recently, a new type of SiC materials with a medium specific surface area and thermal conductivity, called β-SiC, has attracted overgrowing interest as a new class of catalyst support in several catalytic reactions. A primary electron tomography study, performed in usual mode, has revealed a dual surface structure defined by two types of porosities made of networks of connected channels with sizes larger than 50 nm and ink-bottled pores with sizes spanning from 4 to 50 nm. Depending on the solvent nature, metal nanoparticles could be selectively deposited inside one of the two porosities, a fact that illustrates a selective wetting titration of the two types of surfaces by different liquids. The explaining hypothesis that has been put forward was that this selectivity against solvents is related to the pore surface oxidation degree of the two types of pores. A new technique of analytical electron tomography, where the series of projections used to reconstruct the volume of an object is recorded in energy filtered mode (EFTEM), has been implemented to map the poreoxidation state and to correlate it with the morphology and the accessibility of the porous network. Applied, for the first time, at a nanoscale resolution, this technique allowed us to obtain 3D elemental maps of different elements present in the analysed porous grains, in particular oxygen; we found thus that the interconnected channelpores are more rapidly oxidized than the ink-bottled ones. Alternatively, our study highlights the great interest of this method that opens the way for obtaining precise information on the chemical composition of a 3D surface at a nanometer scale.Silicon carbide is a ceramic material that has been widely studied because of its potential applications, ranging from electronics to heterogeneous catalysis. Recently, a new type of SiC materials with a medium specific surface area and thermal conductivity, called β-SiC, has attracted overgrowing interest as a new class of catalyst support in several catalytic reactions. A primary electron tomography study, performed in usual mode, has revealed a dual surface structure defined by two types of porosities made of networks of connected channels with sizes larger than 50 nm and ink-bottled pores with sizes spanning from 4 to 50 nm. Depending on the solvent nature, metal nanoparticles could be selectively deposited inside one of the two porosities, a fact that illustrates a selective wetting titration of the two types of surfaces by different liquids. The explaining hypothesis that has been put forward was that this selectivity against solvents is related to the pore surface oxidation degree of the two types of pores. A new technique of analytical electron tomography, where the series of projections used to reconstruct the volume of an object is recorded in energy filtered mode (EFTEM), has been implemented to map the poreoxidation state and to correlate it with the morphology and the accessibility of the porous network. Applied, for the first time, at a nanoscale resolution, this technique allowed us to obtain 3D elemental maps of different elements present in the analysed porous grains, in particular oxygen; we found thus that the interconnected channelpores are more rapidly oxidized than the ink-bottled ones. Alternatively, our study highlights the great interest of this method that opens the way for obtaining precise information on the chemical composition of a 3D surface at a nanometer scale. Electronic supplementary information (ESI) available: SI-1-SI-4. See DOI: 10.1039/c0nr00449a

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)

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.

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.

Two-dimensional solid-phase extraction strategy for the selective enrichment of aminoglycosides in milk.

PubMed

Shen, Aijin; Wei, Jie; Yan, Jingyu; Jin, Gaowa; Ding, Junjie; Yang, Bingcheng; Guo, Zhimou; Zhang, Feifang; Liang, Xinmiao

2017-03-01

An orthogonal two-dimensional solid-phase extraction strategy was established for the selective enrichment of three aminoglycosides including spectinomycin, streptomycin, and dihydrostreptomycin in milk. A reversed-phase liquid chromatography material (C 18 ) and a weak cation-exchange material (TGA) were integrated in a single solid-phase extraction cartridge. The feasibility of two-dimensional clean-up procedure that experienced two-step adsorption, two-step rinsing, and two-step elution was systematically investigated. Based on the orthogonality of reversed-phase and weak cation-exchange procedures, the two-dimensional solid-phase extraction strategy could minimize the interference from the hydrophobic matrix existing in traditional reversed-phase solid-phase extraction. In addition, high ionic strength in the extracts could be effectively removed before the second dimension of weak cation-exchange solid-phase extraction. Combined with liquid chromatography and tandem mass spectrometry, the optimized procedure was validated according to the European Union Commission directive 2002/657/EC. A good performance was achieved in terms of linearity, recovery, precision, decision limit, and detection capability in milk. Finally, the optimized two-dimensional clean-up procedure incorporated with liquid chromatography and tandem mass spectrometry was successfully applied to the rapid monitoring of aminoglycoside residues in milk. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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 phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors.

PubMed

Aghajanian, Carol; Bell-McGuinn, Katherine M; Burris, Howard A; Siu, Lillian L; Stayner, Lee-Ann; Wheler, Jennifer J; Hong, David S; Kurkjian, Carla; Pant, Shubham; Santiago-Walker, Ademi; Gauvin, Jennifer L; Antal, Joyce M; Opalinska, Joanna B; Morris, Shannon R; Infante, Jeffrey R

2018-04-03

Background We sought to determine the recommended phase II dose (RP2D) and schedule of GSK2141795, an oral pan-AKT kinase inhibitor. Patients and Methods Patients with solid tumors were enrolled in the dose-escalation phase. Pharmacokinetic (PK) analysis after a single dose (Cycle 0) informed dose escalation using accelerated dose titration. Once one grade 2 toxicity or dose-limiting toxicity was observed in Cycle 1, the accelerated dose titration was terminated and a 3 + 3 dose escalation was started. Continuous daily dosing was evaluated along with two intermittent regimens (7 days on/7 days off and 3 times per week). In the expansion phase at RP2D, patients with endometrial or prostate cancer, as well as those with select tumor types with a PIK3CA mutation, AKT mutation or PTEN loss, were enrolled. Patients were evaluated for adverse events (AEs), PK parameters, blood glucose and insulin levels, and tumor response. Results The RP2D of GSK2141795 for once-daily dosing is 75 mg. The most common (>10%) treatment-related AEs included diarrhea, fatigue, vomiting, and decreased appetite. Most AEs were low grade. The frequency of hyperglycemia increased with dose; however, at the RP2D, grade 3 hyperglycemia was only reported in 4% of patients and no grade 4 events were observed. PK characteristics were favorable, with a prolonged half-life and low peak-to-trough ratio. There were two partial responses at the RP2D in patients with either a PIK3CA mutation or PTEN loss. Conclusion GSK2141795 was safe and well-tolerated, with clinical activity seen as monotherapy at the RP2D of 75 mg daily. NCT00920257.

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

Ahn, Sol; Thornburg, Nicholas E.; Li, Zhanyong

In this study by developing structurally well-defined, supported oxide catalysts remains a significant challenge. Here, we report the grafting of Nb(V) oxide sites onto the nodes of the Zr-based metal organic framework (MOF) NU-1000 as a stable, well-defined catalyst support. Nb(V) oxide was deposited with loadings up to 1.6 mmol/g via two post-synthetic methods: atomic layer deposition in a MOF (AIM), and solution-phase grafting in a MOF (SIM). Difference envelope density (DED) measurements indicated that the two synthetic methods resulted in different local structures of the Nb(V) ions within NU-1000. Despite their high Nb(V) loadings, which were equivalent to >60%more » surface coverage, nearly all Nb(V) sites of the MOF-supported catalysts were active sites for alkene epoxidation, as confirmed by phenylphosphonic acid titration. The MOF-supported catalysts were more selective than the control Nb-ZrO 2 catalyst for cyclohexene epoxidation with aqueous H 2O 2, and were far more active on a gravimetric basis.« less

Stable metal–organic framework-supported niobium catalysts

DOE PAGES

Ahn, Sol; Thornburg, Nicholas E.; Li, Zhanyong; ...

2016-10-31

In this study by developing structurally well-defined, supported oxide catalysts remains a significant challenge. Here, we report the grafting of Nb(V) oxide sites onto the nodes of the Zr-based metal organic framework (MOF) NU-1000 as a stable, well-defined catalyst support. Nb(V) oxide was deposited with loadings up to 1.6 mmol/g via two post-synthetic methods: atomic layer deposition in a MOF (AIM), and solution-phase grafting in a MOF (SIM). Difference envelope density (DED) measurements indicated that the two synthetic methods resulted in different local structures of the Nb(V) ions within NU-1000. Despite their high Nb(V) loadings, which were equivalent to >60%more » surface coverage, nearly all Nb(V) sites of the MOF-supported catalysts were active sites for alkene epoxidation, as confirmed by phenylphosphonic acid titration. The MOF-supported catalysts were more selective than the control Nb-ZrO 2 catalyst for cyclohexene epoxidation with aqueous H 2O 2, and were far more active on a gravimetric basis.« less

Role of Arginine 293 and Glutamine 288 in Communication between Catalytic and Allosteric Sites in Yeast Ribonucleotide Reductase

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

Ahmad, Md. Faiz; Kaushal, Prem Singh; Wan, Qun

2012-11-01

Ribonucleotide reductases (RRs) catalyze the rate-limiting step of de novo deoxynucleotide (dNTP) synthesis. Eukaryotic RRs consist of two proteins, RR1 ({alpha}) that contains the catalytic site and RR2 ({beta}) that houses a diferric-tyrosyl radical essential for ribonucleoside diphosphate reduction. Biochemical analysis has been combined with isothermal titration calorimetry (ITC), X-ray crystallography and yeast genetics to elucidate the roles of two loop 2 mutations R293A and Q288A in Saccharomyces cerevisiae RR1 (ScRR1). These mutations, R293A and Q288A, cause lethality and severe S phase defects, respectively, in cells that use ScRR1 as the sole source of RR1 activity. Compared to the wild-typemore » enzyme activity, R293A and Q288A mutants show 4% and 15%, respectively, for ADP reduction, whereas they are 20% and 23%, respectively, for CDP reduction. ITC data showed that R293A ScRR1 is unable to bind ADP and binds CDP with 2-fold lower affinity compared to wild-type ScRR1. With the Q288A ScRR1 mutant, there is a 6-fold loss of affinity for ADP binding and a 2-fold loss of affinity for CDP compared to the wild type. X-ray structures of R293A ScRR1 complexed with dGTP and AMPPNP-CDP [AMPPNP, adenosine 5-({beta},{gamma}-imido)triphosphate tetralithium salt] reveal that ADP is not bound at the catalytic site, and CDP binds farther from the catalytic site compared to wild type. Our in vivo functional analyses demonstrated that R293A cannot support mitotic growth, whereas Q288A can, albeit with a severe S phase defect. Taken together, our structure, activity, ITC and in vivo data reveal that the arginine 293 and glutamine 288 residues of ScRR1 are crucial in facilitating ADP and CDP substrate selection.« less

Field measurement of alkalinity and pH

USGS Publications Warehouse

Barnes, Ivan

1964-01-01

The behavior of electrometric pH equipment under field conditions departs from the behavior predicted from Nernst's law. The response is a linear function of pH, and hence measured pH values may be corrected to true pH if the instrument is calibrated with two reference solutions for each measurement. Alkalinity titrations may also be made in terms of true pH. Standard methods, such as colorimetric titrations, were rejected as unreliable or too cumbersome for rapid field use. The true pH of the end point of the alkalinity titration as a function of temperature, ionic strength, and total alkalinity has been calculated. Total alkalinity in potable waters is the most important factor influencing the end point pH, which varies from 5.38 (0 ? C, 5 ppm (parts per million) HC0a-) to 4.32 (300 ppm HC0a-,35 ? C), for the ranges of variables considered. With proper precautions, the pH may be determined to =i:0.02 pH and the alkalinity to =i:0.6 ppm HCO3- for many naturally occurring bodies of fresh water.

Application of Computers for Experiment Design, Data Acquisition, and Analysis in the Chemistry Laboratory

DTIC Science & Technology

1990-05-01

Obtain Thermistor Operating Characteristics ................................. 82 25. Ag+/Ci" Thermometric Titration ........................... 85 26...Experiment Program for Thermometric Titrations ............... 85 27. Appearance of the Spreadsheet in the Analysis Mode ............ 86 28...rate experiments, carbon dioxide exhalation monitoring, stream turbidity measurement, photosynthesis monitoring, pendulum timing, thermometric titrations

Thermodynamic Basis of Selectivity in the Interactions of Tissue Inhibitors of Metalloproteinases N-domains with Matrix Metalloproteinases-1, -3, and -14*

PubMed Central

Zou, Haiyin; Wu, Ying

2016-01-01

The four tissue inhibitors of metalloproteinases (TIMPs) are potent inhibitors of the many matrixins (MMPs), except that TIMP1 weakly inhibits some MMPs, including MMP14. The broad-spectrum inhibition of MMPs by TIMPs and their N-domains (NTIMPs) is consistent with the previous isothermal titration calorimetric finding that their interactions are entropy-driven but differ in contributions from solvent and conformational entropy (ΔSsolv, ΔSconf), estimated using heat capacity changes (ΔCp). Selective engineered NTIMPs have potential applications for treating MMP-related diseases, including cancer and cardiomyopathy. Here we report isothermal titration calorimetric studies of the effects of selectivity-modifying mutations in NTIMP1 and NTIMP2 on the thermodynamics of their interactions with MMP1, MMP3, and MMP14. The weak inhibition of MMP14 by NTIMP1 reflects a large conformational entropy penalty for binding. The T98L mutation, peripheral to the NTIMP1 reactive site, enhances binding by increasing ΔSsolv but also reduces ΔSconf. However, the same mutation increases NTIMP1 binding to MMP3 in an interaction that has an unusual positive ΔCp. This indicates a decrease in solvent entropy compensated by increased conformational entropy, possibly reflecting interactions involving alternative conformers. The NTIMP2 mutant, S2D/S4A is a selective MMP1 inhibitor through electrostatic effects of a unique MMP-1 arginine. Asp-2 increases reactive site polarity, reducing ΔCp, but increases conformational entropy to maintain strong binding to MMP1. There is a strong negative correlation between ΔSsolv and ΔSconf for all characterized interactions, but the data for each MMP have characteristic ranges, reflecting intrinsic differences in the structures and dynamics of their free and inhibitor-bound forms. PMID:27033700

Comparison of methods for accurate end-point detection of potentiometric titrations

NASA Astrophysics Data System (ADS)

Villela, R. L. A.; Borges, P. P.; Vyskočil, L.

2015-01-01

Detection of the end point in potentiometric titrations has wide application on experiments that demand very low measurement uncertainties mainly for certifying reference materials. Simulations of experimental coulometric titration data and consequential error analysis of the end-point values were conducted using a programming code. These simulations revealed that the Levenberg-Marquardt method is in general more accurate than the traditional second derivative technique used currently as end-point detection for potentiometric titrations. Performance of the methods will be compared and presented in this paper.

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.

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 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

Counting Active Sites on Titanium Oxide-Silica Catalysts for Hydrogen Peroxide Activation through In Situ Poisoning with Phenylphosphonic Acid

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

Eaton, Todd R.; Boston, Andrew M.; Thompson, Anthony B.

2015-06-04

Quantifying specific active sites in supported catalysts improves our understanding and assists in rational design. Supported oxides can undergo significant structural changes as surface densities increase from site-isolated cations to monolayers and crystallites, which changes the number of kinetically relevant sites. Herein, TiO x domains are titrated on TiO x–SiO 2 selectively with phenylphosphonic acid (PPA). An ex situ method quantifies all fluid-accessible TiO x, whereas an in situ titration during cis-cyclooctene epoxidation provides previously unavailable values for the number of tetrahedral Ti sites on which H 2O 2 activation occurs. We use this method to determine the active sitemore » densities of 22 different catalysts with different synthesis methods, loadings, and characteristic spectra and find a single intrinsic turnover frequency for cis-cyclooctene epoxidation of (40±7) h -1. This simple method gives molecular-level insight into catalyst structure that is otherwise hidden when bulk techniques are used.« less

Inverting the planning gradient: adjustment of grasps to late segments of multi-step object manipulations.

PubMed

Mathew, Hanna; Kunde, Wilfried; Herbort, Oliver

2017-05-01

When someone grasps an object, the grasp depends on the intended object manipulation and usually facilitates it. If several object manipulation steps are planned, the first step has been reported to primarily determine the grasp selection. We address whether the grasp can be aligned to the second step, if the second step's requirements exceed those of the first step. Participants grasped and rotated a dial first by a small extent and then by various extents in the opposite direction, without releasing the dial. On average, when the requirements of the first and the second step were similar, participants mostly aligned the grasp to the first step. When the requirements of the second step were considerably higher, participants aligned the grasp to the second step, even though the first step still had a considerable impact. Participants employed two different strategies. One subgroup initially aligned the grasp to the first step and then ceased adjusting the grasp to either step. Another group also initially aligned the grasp to the first step and then switched to aligning it primarily to the second step. The data suggest that participants are more likely to switch to the latter strategy when they experienced more awkward arm postures. In summary, grasp selections for multi-step object manipulations can be aligned to the second object manipulation step, if the requirements of this step clearly exceed those of the first step and if participants have some experience with the task.

A Plan for: A Consumer Conference for Older Adults.

ERIC Educational Resources Information Center

Zarakov, Selma

This document provides a step-by-step description of the planning and implementation of a two day consumer concerns conference for older adults held at Palomar Community College (California). The bulk of the document is made up of practical discussions of such planning phases as facility selection and decoration, conference publicity, snack and…

Comparison of commercial analytical techniques for measuring chlorine dioxide in urban desalinated drinking water.

PubMed

Ammar, T A; Abid, K Y; El-Bindary, A A; El-Sonbati, A Z

2015-12-01

Most drinking water industries are closely examining options to maintain a certain level of disinfectant residual through the entire distribution system. Chlorine dioxide is one of the promising disinfectants that is usually used as a secondary disinfectant, whereas the selection of the proper monitoring analytical technique to ensure disinfection and regulatory compliance has been debated within the industry. This research endeavored to objectively compare the performance of commercially available analytical techniques used for chlorine dioxide measurements (namely, chronoamperometry, DPD (N,N-diethyl-p-phenylenediamine), Lissamine Green B (LGB WET) and amperometric titration), to determine the superior technique. The commonly available commercial analytical techniques were evaluated over a wide range of chlorine dioxide concentrations. In reference to pre-defined criteria, the superior analytical technique was determined. To discern the effectiveness of such superior technique, various factors, such as sample temperature, high ionic strength, and other interferences that might influence the performance were examined. Among the four techniques, chronoamperometry technique indicates a significant level of accuracy and precision. Furthermore, the various influencing factors studied did not diminish the technique's performance where it was fairly adequate in all matrices. This study is a step towards proper disinfection monitoring and it confidently assists engineers with chlorine dioxide disinfection system planning and management.

Reproducibility of NMR Analysis of Urine Samples: Impact of Sample Preparation, Storage Conditions, and Animal Health Status

PubMed Central

Schreier, Christina; Kremer, Werner; Huber, Fritz; Neumann, Sindy; Pagel, Philipp; Lienemann, Kai; Pestel, Sabine

2013-01-01

Introduction. Spectroscopic analysis of urine samples from laboratory animals can be used to predict the efficacy and side effects of drugs. This employs methods combining 1H NMR spectroscopy with quantification of biomarkers or with multivariate data analysis. The most critical steps in data evaluation are analytical reproducibility of NMR data (collection, storage, and processing) and the health status of the animals, which may influence urine pH and osmolarity. Methods. We treated rats with a solvent, a diuretic, or a nephrotoxicant and collected urine samples. Samples were titrated to pH 3 to 9, or salt concentrations increased up to 20-fold. The effects of storage conditions and freeze-thaw cycles were monitored. Selected metabolites and multivariate data analysis were evaluated after 1H NMR spectroscopy. Results. We showed that variation of pH from 3 to 9 and increases in osmolarity up to 6-fold had no effect on the quantification of the metabolites or on multivariate data analysis. Storage led to changes after 14 days at 4°C or after 12 months at −20°C, independent of sample composition. Multiple freeze-thaw cycles did not affect data analysis. Conclusion. Reproducibility of NMR measurements is not dependent on sample composition under physiological or pathological conditions. PMID:23865070

Reproducibility of NMR analysis of urine samples: impact of sample preparation, storage conditions, and animal health status.

PubMed

Schreier, Christina; Kremer, Werner; Huber, Fritz; Neumann, Sindy; Pagel, Philipp; Lienemann, Kai; Pestel, Sabine

2013-01-01

Spectroscopic analysis of urine samples from laboratory animals can be used to predict the efficacy and side effects of drugs. This employs methods combining (1)H NMR spectroscopy with quantification of biomarkers or with multivariate data analysis. The most critical steps in data evaluation are analytical reproducibility of NMR data (collection, storage, and processing) and the health status of the animals, which may influence urine pH and osmolarity. We treated rats with a solvent, a diuretic, or a nephrotoxicant and collected urine samples. Samples were titrated to pH 3 to 9, or salt concentrations increased up to 20-fold. The effects of storage conditions and freeze-thaw cycles were monitored. Selected metabolites and multivariate data analysis were evaluated after (1)H NMR spectroscopy. We showed that variation of pH from 3 to 9 and increases in osmolarity up to 6-fold had no effect on the quantification of the metabolites or on multivariate data analysis. Storage led to changes after 14 days at 4°C or after 12 months at -20°C, independent of sample composition. Multiple freeze-thaw cycles did not affect data analysis. Reproducibility of NMR measurements is not dependent on sample composition under physiological or pathological conditions.

Energetics of phosphate binding to ammonium and guanidinium containing metallo-receptors in water.

PubMed

Tobey, Suzanne L; Anslyn, Eric V

2003-12-03

The design and synthesis of receptors containing a Cu(II) binding site with appended ammonium groups (1) and guanidinium groups (2), along with thermodynamics analyses of anion binding, are reported. Both receptors 1 and 2 show high affinities (10(4) M(-1)) and selectivities for phosphate over other anions in 98:2 water:methanol at biological pH. The binding of the host-guest pairs is proposed to proceed through ion-pairing interactions between the charged functional groups on both the host and the guest. The affinities and selectivities for oxyanions were determined using UV/vis titration techniques. Additionally, thermodynamic investigations indicate that the 1:phosphate complex is primarily entropy driven, while the 2:phosphate complex displays both favorable enthalpy and entropy changes. The thermodynamic data for binding provide a picture of the roles of the host, guest, counterions, and solvent. The difference in the entropy and enthalpy driving forces for the ammonium and guanidinium containing hosts are postulated to derive primarily from differences in the solvation shell of these two groups.

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.

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.

Report of the Fifth Biennial Conference on Chemical Education: Content.

ERIC Educational Resources Information Center

Journal of Chemical Education, 1979

1979-01-01

Two papers are reported on, one dealing with a course on inorganic reaction mechanisms for college seniors, and the other on the set-up necessary to provide students with an automatic potentiometric titration facility. (BB)

Agents Within our Midst

DTIC Science & Technology

2012-03-14

agents; and the development of bio -monitoring protocols for civilian and service personnel during a chemical attack. These efforts have resulted in greater...produced by staphylococcal bacteria that is and is classified as a CDC select agent which has the potential to be used as a biological weapon .1...NMR chemical shift perturbation titrations with Fab (fragment, antigen binding regions) domains of 20B1, 14G8, and 6D3 using deuterated (2H) SEB

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...

Ascorbic Acid as a Standard for Iodometric Titrations. An Analytical Experiment for General Chemistry

NASA Astrophysics Data System (ADS)

Silva, Cesar R.; Simoni, Jose A.; Collins, Carol H.; Volpe, Pedro L. O.

1999-10-01

Ascorbic acid is suggested as the weighable compound for the standardization of iodine solutions in an analytical experiment in general chemistry. The experiment involves an iodometric titration in which iodine reacts with ascorbic acid, oxidizing it to dehydroascorbic acid. The redox titration endpoint is determined by the first iodine excess that is complexed with starch, giving a deep blue-violet color. The results of the titration of iodine solution using ascorbic acid as a calibration standard were compared with the results acquired by the classic method using a standardized solution of sodium thiosulfate. The standardization of the iodine solution using ascorbic acid was accurate and precise, with the advantages of saving time and avoiding mistakes due to solution preparation. The colorless ascorbic acid solution gives a very clear and sharp titration end point with starch. It was shown by thermogravimetric analysis that ascorbic acid can be dried at 393 K for 2 h without decomposition. This experiment allows general chemistry students to perform an iodometric titration during a single laboratory period, determining with precision the content of vitamin C in pharmaceutical formulations.

Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease

PubMed Central

Bushinsky, David A.; Kitzman, Dalane W.; Ruschitzka, Frank; Metra, Marco; Filippatos, Gerasimos; Rossignol, Patrick; Du Mond, Charles; Garza, Dahlia; Berman, Lance; Lainscak, Mitja

2018-01-01

Abstract Aims Hyperkalaemia risk precludes optimal renin–angiotensin–aldosterone system inhibitor use in patients with heart failure (HF), particularly those with chronic kidney disease (CKD). Patiromer is a sodium‐free, non‐absorbed potassium (K+)‐binding polymer approved for the treatment of hyperkalaemia. In PEARL‐HF, patiromer 25.2 g (fixed dose) prevented hyperkalaemia in HF patients with or without CKD initiating spironolactone. The current study evaluated the effectiveness of a lower starting dose of patiromer (16.4 g/day) followed by individualized titration in preventing hyperkalaemia and hypokalaemia when initiating spironolactone. Methods and results This open‐label 8‐week study enrolled 63 patients with CKD, serum K+ 4.3–5.1 mEq/L, and chronic HF, who, based on investigator opinion, should receive spironolactone. Eligible patients started spironolactone 25 mg/day and patiromer 16.8 g/day (divided into two doses), with patiromer titrated to maintain serum K+ 4.0–5.1 mEq/L. Mean (standard deviation) serum K+ was 4.78 (0.51) mEq/L at baseline; weekly values were 4.48–4.70 mEq/L during treatment. Serum K+ of 3.5–5.5 mEq/L at the end of study treatment (primary endpoint) was achieved by 57 (90.5%) patients; 53 (84.1%) had serum K+ 4.0–5.1 mEq/L. One patient (1.6%) developed hypokalaemia, and two patients (3.2%) developed hypomagnesaemia. Spironolactone was increased to 50 mg/day in all patients; 43 (68%) patients required one or more patiromer dose titration. Adverse events (AEs) occurred in 36 (57.1%) patients, with a low rate of discontinuations [four (6.3%) patients]. The most common AE was mild to moderate abdominal discomfort [four (6.3%) patients]. Conclusions In this open‐label study, patiromer 16.8 g/day followed by individualized titration maintained serum K+ within the target range in the majority of patients with HF and CKD, all of whom were uptitrated to spironolactone 50 mg/day, patiromer was well tolerated, with a low incidence of hyperkalaemia, hypokalaemia, and hypomagnesaemia. PMID:29369537

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.

Alterations in Topoisomerase IV and DNA Gyrase in Quinolone-Resistant Mutants of Mycoplasma hominis Obtained In Vitro

PubMed Central

Bébéar, Cécile M.; Renaudin, Hélène; Charron, Alain; Bové, Joseph M.; Bébéar, Christiane; Renaudin, Joel

1998-01-01

Mycoplasma hominis mutants were selected stepwise for resistance to ofloxacin and sparfloxacin, and their gyrA, gyrB, parC, and parE quinolone resistance-determining regions were characterized. For ofloxacin, four rounds of selection yielded six first-, six second-, five third-, and two fourth-step mutants. The first-step mutants harbored a single Asp426→Asn substitution in ParE. GyrA changes (Ser83→Leu or Trp) were found only from the third round of selection. With sparfloxacin, three rounds of selection generated 4 first-, 7 second-, and 10 third-step mutants. In contrast to ofloxacin resistance, GyrA mutations (Ser83→Leu or Ser84→Trp) were detected in the first-step mutants prior to ParC changes (Glu84→Lys), which appeared only after the second round of selection. Further analysis of eight multistep-selected mutants of M. hominis that were previously described (2) revealed that they carried mutations in ParE (Asp426→Asn), GyrA (Ser83→Leu) and ParE (Asp426→Asn), GyrA (Ser83→Leu) and ParC (Ser80→Ile), or ParC (Ser80→Ile) alone, depending on the fluoroquinolone used for selection, i.e., ciprofloxacin, norfloxacin, ofloxacin, or pefloxacin, respectively. These data indicate that in M. hominis DNA gyrase is the primary target of sparfloxacin whereas topoisomerase IV is the primary target of pefloxacin, ofloxacin, and ciprofloxacin. PMID:9736554

Influence of defoliation date and gin-drying temperature on oven moisture and KFT water within cotton cultivars

USDA-ARS?s Scientific Manuscript database

Water measured in lint cotton by Karl Fischer Titration was compared to moisture content measured by standard oven-drying in two cultivars. The cultivars had been defoliated at different times and ginned at two possible temperatures. Ginned lint was further processed to produce mechanically cleaned,...

Kinetic mechanism of the dimeric ATP sulfurylase from plants

PubMed Central

Ravilious, Geoffrey E.; Herrmann, Jonathan; Goo Lee, Soon; Westfall, Corey S.; Jez, Joseph M.

2013-01-01

In plants, sulfur must be obtained from the environment and assimilated into usable forms for metabolism. ATP sulfurylase catalyses the thermodynamically unfavourable formation of a mixed phosphosulfate anhydride in APS (adenosine 5′-phosphosulfate) from ATP and sulfate as the first committed step of sulfur assimilation in plants. In contrast to the multi-functional, allosterically regulated ATP sulfurylases from bacteria, fungi and mammals, the plant enzyme functions as a mono-functional, non-allosteric homodimer. Owing to these differences, here we examine the kinetic mechanism of soybean ATP sulfurylase [GmATPS1 (Glycine max (soybean) ATP sulfurylase isoform 1)]. For the forward reaction (APS synthesis), initial velocity methods indicate a single-displacement mechanism. Dead-end inhibition studies with chlorate showed competitive inhibition versus sulfate and non-competitive inhibition versus APS. Initial velocity studies of the reverse reaction (ATP synthesis) demonstrate a sequential mechanism with global fitting analysis suggesting an ordered binding of substrates. ITC (isothermal titration calorimetry) showed tight binding of APS to GmATPS1. In contrast, binding of PPi (pyrophosphate) to GmATPS1 was not detected, although titration of the E•APS complex with PPi in the absence of magnesium displayed ternary complex formation. These results suggest a kinetic mechanism in which ATP and APS are the first substrates bound in the forward and reverse reactions, respectively. PMID:23789618

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.

Competitive adsorption of dyes and heavy metals on zeolitic structures.

PubMed

Hernández-Montoya, V; Pérez-Cruz, M A; Mendoza-Castillo, D I; Moreno-Virgen, M R; Bonilla-Petriciolet, A

2013-02-15

The adsorption of Acid blue 25, basic blue 9, basic violet 3, Pb(2+), Ni(2+), Zn(2+) and Cd(2+) ions has been studied in single and dye-metal binary solutions using two mineral materials: Clinoptilolite (CL) and ER (Erionite). These zeolites were characterized by FT-IR spectroscopy; potentiometric titration and nitrogen adsorption isotherms at 77 K to obtain their textural parameters. Results indicated that ER has an acidic character and a high specific surface (401 m(2) g(-1)) in contrast with the zeolite CL (21 m(2) g(-1)). Surprisingly, the removal of dyes was very similar for the two zeolites and they showed a considerable selectivity by the basic dyes in comparison with the acid dyes. In the case of heavy metals, ER was more effective in the adsorption process showing a selectivity of: Pb(2+) > Ni(2+) > Zn(2+) > Cd(2+). In the multicomponent adsorption experiments an antagonistic effect was observed in the removal of basic dyes and heavy metals. Particularly, the adsorbed amount of basic violet 3 decreased more significantly when the heavy metals are presents in contrast with the basic blue 9. Copyright © 2012 Elsevier Ltd. All rights reserved.

Does a microprocessor-controlled prosthetic knee affect stair ascent strategies in persons with transfemoral amputation?

PubMed

Aldridge Whitehead, Jennifer M; Wolf, Erik J; Scoville, Charles R; Wilken, Jason M

2014-10-01

Stair ascent can be difficult for individuals with transfemoral amputation because of the loss of knee function. Most individuals with transfemoral amputation use either a step-to-step (nonreciprocal, advancing one stair at a time) or skip-step strategy (nonreciprocal, advancing two stairs at a time), rather than a step-over-step (reciprocal) strategy, because step-to-step and skip-step allow the leading intact limb to do the majority of work. A new microprocessor-controlled knee (Ottobock X2(®)) uses flexion/extension resistance to allow step-over-step stair ascent. We compared self-selected stair ascent strategies between conventional and X2(®) prosthetic knees, examined between-limb differences, and differentiated stair ascent mechanics between X2(®) users and individuals without amputation. We also determined which factors are associated with differences in knee position during initial contact and swing within X2(®) users. Fourteen individuals with transfemoral amputation participated in stair ascent sessions while using conventional and X2(®) knees. Ten individuals without amputation also completed a stair ascent session. Lower-extremity stair ascent joint angles, moment, and powers and ground reaction forces were calculated using inverse dynamics during self-selected strategy and cadence and controlled cadence using a step-over-step strategy. One individual with amputation self-selected a step-over-step strategy while using a conventional knee, while 10 individuals self-selected a step-over-step strategy while using X2(®) knees. Individuals with amputation used greater prosthetic knee flexion during initial contact (32.5°, p = 0.003) and swing (68.2°, p = 0.001) with higher intersubject variability while using X2(®) knees compared to conventional knees (initial contact: 1.6°, swing: 6.2°). The increased prosthetic knee flexion while using X2(®) knees normalized knee kinematics to individuals without amputation during swing (88.4°, p = 0.179) but not during initial contact (65.7°, p = 0.002). Prosthetic knee flexion during initial contact and swing were positively correlated with prosthetic limb hip power during pull-up (r = 0.641, p = 0.046) and push-up/early swing (r = 0.993, p < 0.001), respectively. Participants with transfemoral amputation were more likely to self-select a step-over-step strategy similar to individuals without amputation while using X2(®) knees than conventional prostheses. Additionally, the increased prosthetic knee flexion used with X2(®) knees placed large power demands on the hip during pull-up and push-up/early swing. A modified strategy that uses less knee flexion can be used to allow step-over-step ascent in individuals with less hip strength.

Joint L2,1 Norm and Fisher Discrimination Constrained Feature Selection for Rational Synthesis of Microporous Aluminophosphates.

PubMed

Qi, Miao; Wang, Ting; Yi, Yugen; Gao, Na; Kong, Jun; Wang, Jianzhong

2017-04-01

Feature selection has been regarded as an effective tool to help researchers understand the generating process of data. For mining the synthesis mechanism of microporous AlPOs, this paper proposes a novel feature selection method by joint l 2,1 norm and Fisher discrimination constraints (JNFDC). In order to obtain more effective feature subset, the proposed method can be achieved in two steps. The first step is to rank the features according to sparse and discriminative constraints. The second step is to establish predictive model with the ranked features, and select the most significant features in the light of the contribution of improving the predictive accuracy. To the best of our knowledge, JNFDC is the first work which employs the sparse representation theory to explore the synthesis mechanism of six kinds of pore rings. Numerical simulations demonstrate that our proposed method can select significant features affecting the specified structural property and improve the predictive accuracy. Moreover, comparison results show that JNFDC can obtain better predictive performances than some other state-of-the-art feature selection methods. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Designing of a fluoride selective receptor through molecular orbital engineering

NASA Astrophysics Data System (ADS)

Mishra, Rakesh K.; Kumar, Virendra; Diwan, Uzra; Upadhyay, K. K.; Roy Chowdhury, P. K.

2012-11-01

The stepwise substitution of appropriate groups over the 3-[(2,4-dinitro-phenyl)-hydrazono]-butyric acid ethyl ester (R3) lead receptor R1 which showed selectivity towards fluoride in DMSO. The UV-vis and 1H NMR titration studies revealed the details of the binding between receptor R1 and fluoride. The receptor R1 also recognized fluoride in a toothpaste solution to as low as 50 ppm. The theoretical simulations of recognition event at Density Functional Theory (DFT) level using B3LYP/6-31G** basis set and polarizable continuum model (PCM) approach lead a semi-quantitative match with the experimental results.

Fluorenone based fluorescent probe for selective "turn-on" detection of pyrophosphate and alanine

NASA Astrophysics Data System (ADS)

Daniel Thangadurai, T.; Nithya, I.; Manjubaashini, N.; Bhuvanesh, N.; Bharathi, G.; Nandhakumar, R.; Nataraj, D.

2018-06-01

To sense biologically important entities with different size and dimensions, a fluorenone based fluorescent receptor was designed and synthesized. Probe 1 displayed a distinct fluorescence enhancement emission at 565 nm for pyrophosphate and 530 nm for alanine in polar solvent. The fluorescence titration experiments confirm 1:1 stoichiometric ratio with high-binding constant and very low limit of detection (LoD) values. Receptor 1 showed a highly selective and sensitive recognition to HP2O73 - and to alanine over other competitive anions and amino acids. In addition, the fluorescence lifetime measurement and reversible binding study results support the practical importance of 1.

Highly selective fluorescence turn-on sensor for fluoride detection.

PubMed

Sui, Binglin; Kim, Bosung; Zhang, Yuanwei; Frazer, Andrew; Belfield, Kevin D

2013-04-24

Through click chemistry, triazole and triazolium groups have been explored to recognize anions through C-H···A(-) hydrogen-bonding complexion. Herein, we demonstrate evidence of fluoride-induced deprotonation of a C-H bond and its application in fluoride detection. The combination of fluorene and triazolium units produced a highly selective fluorescence turn-on prototype sensor for fluoride. The interactions between the C-H bond and F(-) were studied by fluorescence spectroscopy and (1)H NMR titrations. Test papers were prepared to detect fluoride in aqueous media at concentrations down to 1.9 ppm, important for estimating whether the fluoride concentration in drinking water is at a safe level.

Method for photo-altering a biological system to improve biological effect

DOEpatents

Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

2000-08-01

Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

Microbiological profiles, pH, and titratable acidity of chorizo and salchichón (two Spanish dry fermented sausages) manufactured with ostrich, deer, or pork meat.

PubMed

Capita, Rosa; Llorente-Marigómez, Sandra; Prieto, Miguel; Alonso-Calleja, Carlos

2006-05-01

Microbial counts, pH, and titratable acidity were determined in 102 Spanish dry fermented sausages (chorizo and salchichón) made with ostrich, deer, or pork meat. Average microbial counts (log CFU per gram) varied from 5.46 +/- 0.24 to 8.25 +/- 0.80 (total viable counts), from 4.79 +/- 0.36 to 7.99 +/- 0.20 (psychrotrophs), from 0.00 +/- 0.00 to 0.99 +/- 1.10 (undetectable values were assumed to be zero) (Enterobacteriaceae), from 0.00 +/- 0.00 to 4.27 +/- 1.47 (enterococci), from 5.15 +/- 1.15 to 8.46 +/- 0.49 (lactic acid bacteria), from 3.08 +/- 0.44 to 6.59 +/- 1.76 (Micrococcaceae), from 2.27 +/- 1.53 to 5.11 +/- 1.81 (molds and yeasts), from 0.00 +/- 0.00 to 2.25 +/- 0.81 (pseudomonads), and from 0.00 +/- 0.00 to 2.78 +/- 0.46 (Brochothrix thermosphacta). Average pH and titratable acidity varied from 5.07 +/- 0.25 to 5.63 +/- 0.51 (pH units) and from 0.30 +/- 0.01 to 0.86 +/- 0.19 (% lactic acid). Both type of sausage (P < 0.05) and species of meat (P < 0.001) influenced microbial counts. Salchich6n samples showed lower average values than chorizo samples for most microbial groups (significant for Enterobacteriaceae, lactic acid bacteria, and B. thermosphacta) and titratable acidity. Sausages made from pork showed the highest microbial loads for total viable counts, psychrotrophs, Enterobacteriaceae, enterococci, lactic acid bacteria, and yeasts and molds. Higher counts were observed only for pseudomonads in ostrich sausages. B. thermosphacta levels were similar for all species of meat. The highest average pH value was observed in sausages made from ostrich meat, and the lowest titratable acidity level was found in pork sausages.

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.

Acid-base titrations of functional groups on the surface of the thermophilic bacterium Anoxybacillus flavithermus: comparing a chemical equilibrium model with ATR-IR spectroscopic data.

PubMed

Heinrich, Hannah T M; Bremer, Phil J; Daughney, Christopher J; McQuillan, A James

2007-02-27

Acid-base functional groups at the surface of Anoxybacillus flavithermus (AF) were assigned from the modeling of batch titration data of bacterial suspensions and compared with those determined from in situ infrared spectroscopic titration analysis. The computer program FITMOD was used to generate a two-site Donnan model (site 1: pKa = 3.26, wet concn = 2.46 x 10(-4) mol g(-1); site 2: pKa = 6.12, wet concn = 6.55 x 10(-5) mol g(-1)), which was able to describe data for whole exponential phase cells from both batch acid-base titrations at 0.01 M ionic strength and electrophoretic mobility measurements over a range of different pH values and ionic strengths. In agreement with information on the composition of bacterial cell walls and a considerable body of modeling literature, site 1 of the model was assigned to carboxyl groups, and site 2 was assigned to amino groups. pH difference IR spectra acquired by in situ attenuated total reflection infrared (ATR-IR) spectroscopy confirmed the presence of carboxyl groups. The spectra appear to show a carboxyl pKa in the 3.3-4.0 range. Further peaks were assigned to phosphodiester groups, which deprotonated at slightly lower pH. The presence of amino groups could not be confirmed or discounted by IR spectroscopy, but a positively charged group corresponding to site 2 was implicated by electrophoretic mobility data. Carboxyl group speciation over a pH range of 2.3-10.3 at two different ionic strengths was further compared to modeling predictions. While model predictions were strongly influenced by the ionic strength change, pH difference IR data showed no significant change. This meant that modeling predictions agreed reasonably well with the IR data for 0.5 M ionic strength but not for 0.01 M ionic strength.

A method to switch from oral dopamine agonists to rotigotine in patients with restless legs syndrome and mild augmentation.

PubMed

Winkelman, John W; Mackie, Susan E; Mei, Leslie A; Platt, Samuel; Schoerning, Laura

2016-08-01

We examined the short- and long-term efficacy and tolerability of a cross-titration algorithm from oral dopamine agonists to the rotigotine transdermal patch in patients dissatisfied with their restless legs syndrome (RLS) treatment, predominantly with mild augmentation. Patients with RLS (n = 20) were recruited at a single site. The cross-titration consisted of decreasing oral dopaminergic agents (ropinirole by 1 mg or pramipexole by 0.25 mg) and increasing rotigotine by 1 mg every two days. Efficacy and adverse events (AEs) were assessed at one, three, six and 12 months after the switch. Patients had moderate-severe RLS symptoms at the baseline (mean international restless legs syndrome (IRLS) score 19.4 ± 5.5); 85% had augmentation and 45% reported afternoon RLS symptoms. The baseline mean pramipexole equivalent dose was 0.6 ± 0.3 mg. At Week 5, 85% (17/20) had successfully switched from their oral dopamine agonist to rotigotine (mean dose 2.5 ± 0.6 mg; change in IRLS score: -6.7 ± 8.4, p = 0.002); 14 patients were CGI-I responders (much or very much improved). Three patients withdrew due to lack of efficacy. Twelve months after cross-titration, 10 patients continued on rotigotine, of whom four required either higher doses of rotigotine or supplemental RLS medication compared with their optimal Week 5 dose; five patients withdrew due to AEs and two due to lack of efficacy. A cross-titration to rotigotine was efficacious after five weeks in 70% of patients dissatisfied with RLS treatment, most of whom had mild augmentation. At one year following the medication switch, 50% had discontinued rotigotine due to lack of continued efficacy or side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

The Computer Bulletin Board. Modified Gran Plots of Very Weak Acids on a Spreadsheet.

ERIC Educational Resources Information Center

Chau, F. T.; And Others

1990-01-01

Presented are two applications of computer technology to chemistry instruction: the use of a spreadsheet program to analyze acid-base titration curves and the use of database software to catalog stockroom inventories. (CW)

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…

Quantitative Analysis of Sulfate in Water by Indirect EDTA Titration

ERIC Educational Resources Information Center

Belle-Oudry, Deirdre

2008-01-01

The determination of sulfate concentration in water by indirect EDTA titration is an instructive experiment that is easily implemented in an analytical chemistry laboratory course. A water sample is treated with excess barium chloride to precipitate sulfate ions as BaSO[subscript 4](s). The unprecipitated barium ions are then titrated with EDTA.…

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.

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…

Thermodynamics and solvent linkage of macromolecule-ligand interactions

PubMed Central

Duff, Michael R.; Howell, Elizabeth E.

2014-01-01

Binding involves two steps, desolvation and association. While water is ubiquitous and occurs at high concentration, it is typically ignored. In vitro experiments typically use infinite dilution conditions, while in vivo, the concentration of water is decreased due to the presence of high concentrations of molecules in the cellular milieu. This review discusses isothermal titration calorimetry approaches that address the role of water in binding. For example, use of D2O allows the contribution of solvent reorganization to the enthalpy component to be assessed. Further, the addition of osmolytes will decrease the water activity of a solution and allow effects on Ka to be determined. In most cases, binding becomes tighter in the presence of osmolytes as the desolvation penalty associated with binding is minimized. In other cases, the osmolytes prefer to interact with the ligand or protein, and if their removal is more difficult than shedding water, then binding can be weakened. These complicating layers can be discerned by different slopes in ln(Ka) vs osmolality plots and by differential scanning calorimetry in the presence of the osmolyte. PMID:25462561

Accumulation of phosphatidylcholine on gut mucosal surface is not dominated by electrostatic interactions.

PubMed

Korytowski, Agatha; Abuillan, Wasim; Amadei, Federico; Makky, Ali; Gumiero, Andrea; Sinning, Irmgard; Gauss, Annika; Stremmel, Wolfgang; Tanaka, Motomu

2017-05-01

The accumulation of phosphatidylcholine (PC) in the intestinal mucus layer is crucial for the protection of colon epithelia from the bacterial attack. It has been reported that the depletion of PC is a distinct feature of ulcerative colitis. Here we addressed the question how PC interacts with its binding proteins, the mucins, which may establish the hydrophobic barrier against colonic microbiota. In the first step, the interactions of dioleoylphosphatidylcholine (DOPC) with two mucin preparations from porcine stomach, have been studied using dynamic light scattering, zeta potential measurement, and Langmuir isotherms, suggesting that mucin binds to the surface of DOPC vesicles. The enthalpy of mucin-PC interaction could be determined by isothermal titration calorimetry. The high affinity to PC found for both mucin types seems reasonable, as they mainly consist of mucin 2, a major constituent of the flowing mucus. Moreover, by the systematic variation of net charges, we concluded that the zwitterionic DOPC has the strongest binding affinity that cannot be explained within the electrostatic interactions between charged molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Highly efficient binuclear ruthenium catalyst for water oxidation.

PubMed

Sander, Anett C; Maji, Somnath; Francàs, Laia; Böhnisch, Torben; Dechert, Sebastian; Llobet, Antoni; Meyer, Franc

2015-05-22

Water splitting is one of the key steps in the conversion of sunlight into a usable renewable energy carrier such as dihydrogen or more complex chemical fuels. Developing rugged and highly efficient catalysts for the oxidative part of water splitting, the water oxidation reaction generating dioxygen, is a major challenge in the field. Herein, we introduce a new, and rationally designed, pyrazolate-based diruthenium complex with the highest activity in water oxidation catalysis for binuclear systems reported to date. Single-crystal X-ray diffraction showed favorable preorganization of the metal ions, well suited for binding two water molecules at a distance adequate for OO bond formation; redox titrations as well as spectroelectrochemistry allowed characterization of the system in several oxidation states. Low oxidation potentials reflect the trianionic character of the elaborate compartmental pyrazolate ligand furnished with peripheral carboxylate groups. Water oxidation has been mediated both by a chemical oxidant (Ce(IV) )-by means of manometry and a Clark electrode for monitoring the dioxygen production-and electrochemically with impressive activities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermodynamics and solvent linkage of macromolecule–ligand interactions

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

Duff, Michael R.; Howell, Elizabeth E.

Binding involves two steps, desolvation and association. While water is ubiquitous and occurs at high concentration, it is typically ignored. In vitro experiments typically use infinite dilution conditions, while in vivo, the concentration of water is decreased due to the presence of high concentrations of molecules in the cellular milieu. Our paper discusses isothermal titration calorimetry approaches that address the role of water in binding. For example, use of D2O allows the contribution of solvent reorganization to the enthalpy component to be assessed. Furthermore, the addition of osmolytes will decrease the water activity of a solution and allow effects onmore » Ka to be determined. In most cases, binding becomes tighter in the presence of osmolytes as the desolvation penalty associated with binding is minimized. In other cases, the osmolytes prefer to interact with the ligand or protein, and if their removal is more difficult than shedding water, then binding can be weakened. Lastly, these complicating layers can be discerned by different slopes in ln(Ka) vs osmolality plots and by differential scanning calorimetry in the presence of the osmolyte.« less

Microprocessor-controlled hemodynamics: a step towards improved efficiency and safety.

PubMed

Keogh, B E; Jacobs, J; Royston, D; Taylor, K M

1989-02-01

Manual titration of sodium nitroprusside (SNP) is widely used for treatment of hypertension following cardiac surgery. This study compared conventional manual control with control by a research prototype of an automatic infusion module based on a proportional plus integral plus derivative (PID) negative feedback loop. Two groups of coronary artery bypass patients requiring SNP for postoperative hypertension were studied prospectively. In the first group, hypertension was controlled by manual adjustment of the SNP infusion rate, and in the second, the infusion rate was controlled automatically. The actual and desired mean arterial pressures (MAP) over consecutive ten-second epochs were recorded during the period of infusion. The MAP was maintained within 10% of the desired MAP 45.8% of the time in the manual group, compared with 90.0% in the automatic group, and the mean percent error in the automatic group was significantly less than in the manual group (P less than 0.01). It is concluded that adoption of such systems will result in improved patient safety and may facilitate more effective distribution of nursing staff within intensive care units.

Thermodynamics and solvent linkage of macromolecule–ligand interactions

DOE PAGES

Duff, Michael R.; Howell, Elizabeth E.

2014-11-21

Binding involves two steps, desolvation and association. While water is ubiquitous and occurs at high concentration, it is typically ignored. In vitro experiments typically use infinite dilution conditions, while in vivo, the concentration of water is decreased due to the presence of high concentrations of molecules in the cellular milieu. Our paper discusses isothermal titration calorimetry approaches that address the role of water in binding. For example, use of D2O allows the contribution of solvent reorganization to the enthalpy component to be assessed. Furthermore, the addition of osmolytes will decrease the water activity of a solution and allow effects onmore » Ka to be determined. In most cases, binding becomes tighter in the presence of osmolytes as the desolvation penalty associated with binding is minimized. In other cases, the osmolytes prefer to interact with the ligand or protein, and if their removal is more difficult than shedding water, then binding can be weakened. Lastly, these complicating layers can be discerned by different slopes in ln(Ka) vs osmolality plots and by differential scanning calorimetry in the presence of the osmolyte.« less

Yoghurts with addition of selected vegetables: acidity, antioxidant properties and sensory quality.

PubMed

Najgebauer-Lejko, Dorota; Grega, Tadeusz; Tabaszewska, Małgorzata

2014-01-01

Yoghurt is a fermented milk of unique sensory, nutritive and dietetic value offered in a variety of types and in different flavours. Vegetables belong to the group of food products rich in antioxidant substances (e.g., vitamin C, carotenoids, tocopherols, polyphenols) which regular consumption lowers the risk of many diseases including cancers and cardiovascular disorders. The aim of the present work was to manufacture and assess the acidity, sensory quality and antioxidant capacity of yoghurts with addition of selected vegetables during 2-week refrigerated storage. The vegetable preparations (carrot, pumpkin, broccoli and red sweet pepper) were added to the cow's milk fermented using DVS type yoghurt culture after initial cooling to 15-20°C in the amount of 10% (w/w). The following analyses were performed: determination of pH, titratable acidity, antioxidant activity by ferric reducing antioxidant power (FRAP) and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) method as well as sensory evaluation and were conducted after 1, 7 and 14 days of cold storage. The yoghurt supplementation with selected vegetables had no significant effect on the pH and titratable acidity level. The highest ability to scavenge DPPH radicals was stated for yoghurts with broccoli and red sweet pepper. The latter treatment gained the highest notes in sensory evaluation. All vegetable yoghurts were characterised by higher than the natural yoghurt FRAP values measured directly after production. However, the level of this parameter significantly decreased after storage. The red sweet pepper additive was the most beneficial regarding antioxidant properties and organoleptic acceptance of the studied yoghurts.

Construction of a new selective coated disk electrode for Ag (I) based on modified polypyrrole-carbon nanotubes composite with new lariat ether.

PubMed

Abbaspour, A; Tashkhourian, J; Ahmadpour, S; Mirahmadi, E; Sharghi, H; Khalifeh, R; Shahriyari, M R

2014-01-01

A poly (vinyl chloride) (PVC) matrix membrane ion-selective electrode for silver (I) ion is fabricated based on modified polypyrrole - multiwalled carbon nanotubes composite with new lariat ether. This sensor has a Nernstian slope of 59.4±0.5mV/decade over a wide linear concentration range of 1.0×10(-7) to 1.0×10(-1)molL(-1) for silver (I) ion. It has a short response time of about 8.0s and can be used for at least 50days. The detection limit is 9.3×10(-8)molL(-1) for silver (I) ion, and the electrode was applicable in the wide pH range of 1.6 -7.7. The electrode shows good selectivity for silver ion against many cations such as Hg (II), which usually imposes serious interference in the determination of silver ion concentration. The use of multiwalled carbon nanotubes (MWCNTs) in a polymer matrix improves the linear range and sensitivity of the electrode. In addition by coating the solid contact with a layer of the polypyrrole (Ppy) before coating the membrane on it, not only did it reduce the drift in potential, but a shorter response time was also resulted. The proposed electrode was used as an indicator electrode for potentiometric titration of silver ions with chloride anions and in the titration of mixed halides. This electrode was successfully applied for the determination of silver ions in silver sulphadiazine as a burning cream. © 2013.

The Synthesis of 2-acetyl-1,4-naphthoquinone: A Multi-step Synthesis.

ERIC Educational Resources Information Center

Green, Ivan R.

1982-01-01

Outlines 2 procedures for synthesizing 2-acetyl-1,4-naphthoquinone to compare relative merits of the two pathways. The major objective of the exercise is to demonstrate that certain factors should be considered when selecting a pathway for synthesis including availability of starting materials, cost of reagents, number of steps involved,…

Integrated feature extraction and selection for neuroimage classification

NASA Astrophysics Data System (ADS)

Fan, Yong; Shen, Dinggang

2009-02-01

Feature extraction and selection are of great importance in neuroimage classification for identifying informative features and reducing feature dimensionality, which are generally implemented as two separate steps. This paper presents an integrated feature extraction and selection algorithm with two iterative steps: constrained subspace learning based feature extraction and support vector machine (SVM) based feature selection. The subspace learning based feature extraction focuses on the brain regions with higher possibility of being affected by the disease under study, while the possibility of brain regions being affected by disease is estimated by the SVM based feature selection, in conjunction with SVM classification. This algorithm can not only take into account the inter-correlation among different brain regions, but also overcome the limitation of traditional subspace learning based feature extraction methods. To achieve robust performance and optimal selection of parameters involved in feature extraction, selection, and classification, a bootstrapping strategy is used to generate multiple versions of training and testing sets for parameter optimization, according to the classification performance measured by the area under the ROC (receiver operating characteristic) curve. The integrated feature extraction and selection method is applied to a structural MR image based Alzheimer's disease (AD) study with 98 non-demented and 100 demented subjects. Cross-validation results indicate that the proposed algorithm can improve performance of the traditional subspace learning based classification.

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.

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.

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.

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.

Supervised group Lasso with applications to microarray data analysis

PubMed Central

Ma, Shuangge; Song, Xiao; Huang, Jian

2007-01-01

Background A tremendous amount of efforts have been devoted to identifying genes for diagnosis and prognosis of diseases using microarray gene expression data. It has been demonstrated that gene expression data have cluster structure, where the clusters consist of co-regulated genes which tend to have coordinated functions. However, most available statistical methods for gene selection do not take into consideration the cluster structure. Results We propose a supervised group Lasso approach that takes into account the cluster structure in gene expression data for gene selection and predictive model building. For gene expression data without biological cluster information, we first divide genes into clusters using the K-means approach and determine the optimal number of clusters using the Gap method. The supervised group Lasso consists of two steps. In the first step, we identify important genes within each cluster using the Lasso method. In the second step, we select important clusters using the group Lasso. Tuning parameters are determined using V-fold cross validation at both steps to allow for further flexibility. Prediction performance is evaluated using leave-one-out cross validation. We apply the proposed method to disease classification and survival analysis with microarray data. Conclusion We analyze four microarray data sets using the proposed approach: two cancer data sets with binary cancer occurrence as outcomes and two lymphoma data sets with survival outcomes. The results show that the proposed approach is capable of identifying a small number of influential gene clusters and important genes within those clusters, and has better prediction performance than existing methods. PMID:17316436

Monitoring of intratidal lung mechanics: a Graphical User Interface for a model-based decision support system for PEEP-titration in mechanical ventilation.

PubMed

Buehler, S; Lozano-Zahonero, S; Schumann, S; Guttmann, J

2014-12-01

In mechanical ventilation, a careful setting of the ventilation parameters in accordance with the current individual state of the lung is crucial to minimize ventilator induced lung injury. Positive end-expiratory pressure (PEEP) has to be set to prevent collapse of the alveoli, however at the same time overdistension should be avoided. Classic approaches of analyzing static respiratory system mechanics fail in particular if lung injury already prevails. A new approach of analyzing dynamic respiratory system mechanics to set PEEP uses the intratidal, volume-dependent compliance which is believed to stay relatively constant during one breath only if neither atelectasis nor overdistension occurs. To test the success of this dynamic approach systematically at bedside or in an animal study, automation of the computing steps is necessary. A decision support system for optimizing PEEP in form of a Graphical User Interface (GUI) was targeted. Respiratory system mechanics were analyzed using the gliding SLICE method. The resulting shapes of the intratidal compliance-volume curve were classified into one of six categories, each associated with a PEEP-suggestion. The GUI should include a graphical representation of the results as well as a quality check to judge the reliability of the suggestion. The implementation of a user-friendly GUI was successfully realized. The agreement between modelled and measured pressure data [expressed as root-mean-square (RMS)] tested during the implementation phase with real respiratory data from two patient studies was below 0.2 mbar for data taken in volume controlled mode and below 0.4 mbar for data taken in pressure controlled mode except for two cases with RMS < 0.6 mbar. Visual inspections showed, that good and medium quality data could be reliably identified. The new GUI allows visualization of intratidal compliance-volume curves on a breath-by-breath basis. The automatic categorisation of curve shape into one of six shape-categories provides the rational decision-making model for PEEP-titration.

Adjunctive lacosamide for focal epilepsy: an open-label trial evaluating the impact of flexible titration and dosing on safety and seizure outcomes.

PubMed

Baulac, Michel; Coulbaut, Safia; Doty, Pamela; McShea, Cindy; De Backer, Marc; Bartolomei, Fabrice; Vlaicu, Mihaela

2017-06-01

To evaluate the safety and effectiveness of lacosamide in a real-life setting with the use of a flexible dose titration schedule and individualised maintenance doses up to the maximum approved dose of 400 mg/day. Adults with a diagnosis of focal seizures, with or without secondary generalization, were enrolled in this open-label Phase IV trial (NCT01235403). Lacosamide was initiated at 100 mg/day (50 mg bid) and uptitrated over a 12-week period to 200, 300 or 400 mg/day, based on safety and seizure control. Although dose increases were to be in increments of 100 mg/day, intermediate doses were permitted at each escalation step for one week for patients known to be particularly sensitive to starting new AEDs. After receiving a stable, effective dose for three weeks, patients entered the 12-week maintenance period. Primary outcomes were incidence of treatment-emergent adverse events (TEAEs) and withdrawal due to TEAEs. Seizure outcomes, all secondary, were median focal seizure frequency, ≥50% reduction in focal seizure frequency, and seizure freedom. One hundred patients with a mean age of 44 years were enrolled and 74 completed the trial. The incidence of TEAEs was 64.0% (n=100), with the most frequently reported (≥5% of patients) being dizziness, headache, and asthenia. Fourteen patients withdrew due to TEAEs, most frequently due to dizziness (six patients; 6.0%), vomiting (two patients; 2%), and tremor (two patients; 2%). Among patients with baseline and maintenance phase seizure data (n=75), median reduction in focal seizure frequency from baseline was 69.7% and the ≥50% responder rate was 69.3%. Among 74 patients who completed the maintenance phase, 21 (28.4%) were seizure-free. Flexible lacosamide dosing in this open-label trial was associated with a favourable tolerability and safety profile; the nature of the TEAEs was consistent with that observed in previous pivotal trials. Treatment with lacosamide was also associated with effective seizure control.

Coumarin-indole conjugate donor-acceptor system: Synthesis, photophysical properties, anion sensing ability, theoretical and biological activity studies of two coumarin-indole based push-pull dyes

NASA Astrophysics Data System (ADS)

Aksungur, Tuğçe; Aydıner, Burcu; Seferoğlu, Nurgül; Özkütük, Müjgan; Arslan, Leyla; Reis, Yasemin; Açık, Leyla; Seferoğlu, Zeynel

2017-11-01

Two coumarin-indole conjugate fluorescent dyes having donor-acceptor-donor (D-A-D) (CI-1 and CI-2) were synthesized, and characterized using IR, 1H/13C NMR and HRMS. The absorption and emission properties of the dyes were determined in different solvents. The anion sensitivity and selectivity of the dyes were studied with some anions (CN-, F-, AcO-, Cl-, Br-, I-, HSO4- and H2PO4-) in DMSO, and their interaction mechanisms were evaluated by spectrophotometric and 1H NMR titration techniques. In addition, the molecular and electronic structures of CI-1, as well as the molecular complexes of CI-1, formed with the anions (F- and AcO-), were obtained theoretically and confirmed by DFT and TD-DFT calculations. CI-1 behaves as a colorimetric chemosensor for selective and sensitive detection of CN- in DMSO/H2O (9:1) over other competing anions such as F- and AcO-. However, only CN- interacts with chromophore CI-2 via Michael addition and the main absorption maxima shifts hypsochromically with an observed distinctive color change from orange to yellow. For using as a optic dye, the thermal stability properties of the dyes was determined by TGA (Thermal Gravimetric Analysis). Antimicrobial, antifungal and DNA-ligand interaction studies of the dyes were also examined. The dyes cause conformational changes on DNA and selectively bind to nucleotides of A/A and G/G.

Titanium (III) cation selective electrode based on synthesized tris(2pyridyl) methylamine ionophore and its application in water samples

PubMed Central

Rezayi, Majid; Karazhian, Reza; Abdollahi, Yadollah; Narimani, Leila; Sany, Seyedeh Belin Tavakoly; Ahmadzadeh, Saeid; Alias, Yatimah

2014-01-01

The introduction of low detection limit ion selective electrodes (ISEs) may well pave the way for the determination of trace targets of cationic compounds. This research focuses on the detection of titanium (III) cation using a new PVC-membrane sensor based on synthesized tris(2pyridyl) methylamine (tpm) ionophore. The application and validation of the proposed sensor was done using potentiometric titration, inductively coupled plasma atomic emission spectrometry (ICP-AES), and atomic absorption spectrometry (AAS). The membrane sensor exhibited a Nernstian response to the titanium (III) cation over a concentration range of 1.0 × 10−6–1.0 × 10−2 M and pH range from 1–2.5. The Nernstian slope, the lower of detection (LOD), and the response time (t95%) of the proposed sensor were 29.17 ± 0.24 mV/dec, 7.9 × 10−7 M, and 20 s, respectively. The direct determination of 4–39 μg/ml of titanium (III) standard solution showed an average recovery of 94.60 and a mean relative standard deviation of 1.8 at 100.0 μg/ml. Finally, the utilization of the electrodes as end-point indicators for potentiometric titration with EDTA solutions for titanium (III) sensor was successfully carried out. PMID:24722576

Binding Mode and Selectivity of a Scorpiand-Like Polyamine Ligand to Single- and Double-Stranded DNA and RNA: Metal- and pH-Driven Modulation.

PubMed

Inclán, Mario; Guijarro, Lluis; Pont, Isabel; Frías, Juan C; Rotger, Carmen; Orvay, Francisca; Costa, Antoni; García-España, Enrique; Albelda, M Teresa

2017-11-13

The interaction of a polyazacyclophane ligand having an ethylamine pendant arm functionalized with an anthryl group (L), with the single-stranded polynucleotides polyA, polyG, polyU, and polyC as well as with the double-stranded polynucleotides polyA-polyU, poly(dAT) 2 , and poly(dGC) 2 has been followed by UV/Vis titration, steady state fluorescence spectroscopy, and thermal denaturation measurements. In the case of the single-stranded polynucleotides, the UV/Vis and fluorescence titrations permit to distinguish between sequences containing purine and pyrimidine bases. For the double-stranded polynucleotides the UV/Vis measurements show for all of them hypochromicity and bathochromic shifts. However, the fluorescence studies reveal that both polyA-polyU and poly(dAT) 2 induce a twofold increase in the fluorescence, whereas interaction of poly(dGC) 2 with the ligand L induces a quenching of the fluorescence. Cu 2+ modulates the interaction with the double-stranded polynucleotides due to the conformation changes that its coordination induces in compound L. In general, the spectroscopic studies show that intercalation seems to be blocked by the formation of the metal complex. All these features suggest the possibility of using compound L as a sequence-selective fluorescence probe. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of probiotics, included in peanut butter, on the fate of selected Salmonella and Listeria strains under simulated gastrointestinal conditions.

PubMed

Klu, Y A K; Chen, J

2016-04-01

This study observed the behaviour of probiotics and selected bacterial pathogens co-inoculated into peanut butter during gastrointestinal simulation. Peanut butter homogenates co-inoculated with Salmonella/Listeria strains (5 log CFU ml(-1) ) and lyophilized or cultured probiotics (9 log CFU ml(-1) ) were exposed to simulated gastrointestinal conditions for 24 h at 37°C. Sample pH, titratable acidity and pathogen populations were determined. Agar diffusion assay was performed to assess the inhibitory effect of probiotic culture supernatants with either natural (3·80 (Lactobacillus), 3·78 (Bifidobacteirum) and 5·17 (Streptococcus/Lactococcus)) or neutralized (6·0) pH. Antibacterial effect of crude bacteriocin extracts were also evaluated against the pathogens. After 24 h, samples with probiotics had lower pH and higher titratable acidity than those without probiotics. The presence of probiotics caused a significant reduction (P < 0·05) in pathogen populations. Supernatants of Bifidobacterium and Lactobacillus cultures inhibited pathogen growth; however, the elevation of pH diminished their antibacterial activities. Crude bacteriocin extracts had a strain-specific inhibitory effect only towards Listeria monocytogenes. Probiotics in 'peanut butter' survived simulated gastrointestinal conditions and inhibited the growth of Salmonella/Listeria. Peanut butter is a plausible carrier to deliver probiotics to improve the gastrointestinal health of children in developing countries. © 2016 The Society for Applied Microbiology.

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.

Complexation of copper by aquatic humic substances from different environments

USGS Publications Warehouse

McKnight, Diane M.; Feder, Gerald L.; Thurman, E. Michael; Wershaw, Robert L.

1983-01-01

The copper-complexing properties of aquatic humic substances isolated from eighteen different environments were characterized by potentiometric titration, using a cupric ion selective electrode. Potentiometric data were analyzed using FITEQL, a computer program for the determination of chemical equilibrium constants from experimental data. All the aquatic humic substances could be modelled as having two types of Cu(II)-binding sites: one with K equal to about 106 and a concentration of 1.0 ± 0.4 × 10−6 M(mg C)−1 and another with K equal to about 108 and a concentration of 2.6 ± 1.6 × 10−7 M(mg C)−1.A method is described for estimating the Cu(II)-binding sites associated with dissolved humic substances in natural water based on a measurement of dissolved organic carbon, which may be helpful in evaluating chemical processes controlling speciation of Cu and bioavailability of Cu to aquatic organisms.

Asphaltene dispersants as demulsification aids

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

Manek, M.B.

1995-11-01

Destabilization of petroleum asphaltenes may cause a multitude of problems in crude oil recovery and production. One major problem is their agglomeration at the water-oil interface of crude oil emulsions. Once agglomeration occurs, destabilized asphaltenes can form a thick pad in the dehydration equipment, which significantly reduces the demulsification rate. Certain polymeric dispersants increase asphaltene solubilization in hydrocarbon media, and when used in conjunction with emulsion breakers, facilitate the demulsification process. Two case studies are presented that demonstrate how asphaltene dispersants can efficiently inhibit pad formation and help reduce demulsifier dosage. Criteria for dispersant application and selection are discussed, whichmore » include the application of a novel laboratory technique to assess asphaltene stabilization in the crude oil. The technique monitors asphaltene agglomeration while undergoing titration with an incompatible solvent (precipitant). The method was used to evaluate stabilization of asphaltenes in the crude oil and to screen asphaltene dispersants.« less

Gas chromatographic determination of carboxylic acid chlorides and residual carboxylic acid precursors used in the production of some penicillins.

PubMed

Lauback, R G; Balitz, D F; Mays, D L

1976-05-01

An improved gas chromatographic method is described for the simultaneous determination of carboxylic acid chlorides and related carboxylic acids used in the production of some commercial semisynthetic penicillins. The acid chloride reacts with diethylamine to form the corresponding diethylamide. Carboxylic acid impurities are converted to trimethylsilyl esters. The two derivatives are separated and quantitated in the same chromatographic run. This method, an extension of the earlier procedure of Hishta and Bomstein (1), has been applied to the acid chlorides used to make oxacillin, cloxacillin, dicloxacillin, and methicillin (Figure 1); it shows promise of application to other acid chlorides. The determination is more selective than the usual titration methods, which do not differentiate among acids with similar pK's. Relative standard deviations of the acid chloride determination are 1.0-2.5%. Residual carboxylic acid can be repetitively determined within a range of 0.6% absolute.

A two-step initial mass function:. Consequences of clustered star formation for binary properties

NASA Astrophysics Data System (ADS)

Durisen, R. H.; Sterzik, M. F.; Pickett, B. K.

2001-06-01

If stars originate in transient bound clusters of moderate size, these clusters will decay due to dynamic interactions in which a hard binary forms and ejects most or all the other stars. When the cluster members are chosen at random from a reasonable initial mass function (IMF), the resulting binary characteristics do not match current observations. We find a significant improvement in the trends of binary properties from this scenario when an additional constraint is taken into account, namely that there is a distribution of total cluster masses set by the masses of the cloud cores from which the clusters form. Two distinct steps then determine final stellar masses - the choice of a cluster mass and the formation of the individual stars. We refer to this as a ``two-step'' IMF. Simple statistical arguments are used in this paper to show that a two-step IMF, combined with typical results from dynamic few-body system decay, tends to give better agreement between computed binary characteristics and observations than a one-step mass selection process.

The site-specific basicity of thyroid hormones and their precursors as regulators of their biological functions.

PubMed

Tóth, Gergo; Hosztafi, Sándor; Kovács, Zsuzsanna; Noszál, Béla

2012-03-05

The complete macro- and microequilibrium analyses of thyroxine, liothyronine, reverse liothyronine and their biological precursors--diiodotyrosine, monoiodotyrosine and tyrosine are presented. Their biosyntheses, receptor- and transport protein-binding are shown to be distinctively dependent on the phenolate basicity. The protonation macroconstants were determined by (1)H NMR-pH and/or UV-pH titrations. Microconstants of the minor microspecies were determined by deductive methods, in which O-methylated and carboxymethylated derivatives were synthesized, and the combination of their NMR-pH and UV-pH titration provided the experimental base to evaluate all the microconstants. NMR-pH profiles, macro-, and microscopic protonation schemes, and species-specific diagrams are included. Biosyntheses of the thyroid hormones take place by oxidative coupling of two iodotyrosine residues catalyzed by thyreoperoxidase in thyreoglobulin. On the grounds of our phenolate microconstants of precursors the thyroxine over liothyronine ratio needs to be 9:1 after their biosynthesis in thyroid gland, which is in good agreement with biochemical data. The microconstants show that the phenolates are in proton donor (-OH) form in liothyronine whereas they occur in proton acceptor (-O(-)) form in thyroxine at the pH of blood. These facts explain several facts that have previously been empirically known: the affinity of liothyronine for the receptor is higher than that of thyroxine, the affinity of thyroxine for the transport proteins is higher than that of liothyronine and the selectivity of thyroxine for the OATP1C1 organic anion transporter is higher than that of liothyronine. Copyright © 2011 Elsevier B.V. All rights reserved.

Discovery of a novel general anesthetic chemotype using high-throughput screening.

PubMed

McKinstry-Wu, Andrew R; Bu, Weiming; Rai, Ganesha; Lea, Wendy A; Weiser, Brian P; Liang, David F; Simeonov, Anton; Jadhav, Ajit; Maloney, David J; Eckenhoff, Roderic G

2015-02-01

The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures. Using a novel high-throughput screen employing the fluorescent anesthetic 1-aminoanthracene and apoferritin as a surrogate for on-pathway anesthetic protein target(s), we screened a 350,000 compound library for competition with 1-aminoanthracene-apoferritin binding. Hit compounds meeting structural criteria had their binding affinities for apoferritin quantified with isothermal titration calorimetry and were tested for γ-aminobutyric acid type A receptor binding using a flunitrazepam binding assay. Chemotypes with a strong presence in the top 700 and exhibiting activity via isothermal titration calorimetry were selected for medicinal chemistry optimization including testing for anesthetic potency and toxicity in an in vivo Xenopus laevis tadpole assay. Compounds with low toxicity and high potency were tested for anesthetic potency in mice. From an initial chemical library of more than 350,000 compounds, we identified 2,600 compounds that potently inhibited 1-aminoanthracene binding to apoferritin. A subset of compounds chosen by structural criteria (700) was successfully reconfirmed using the initial assay. Based on a strong presence in both the initial and secondary screens the 6-phenylpyridazin-3(2H)-one chemotype was assessed for anesthetic activity in tadpoles. Medicinal chemistry efforts identified four compounds with high potency and low toxicity in tadpoles, two were found to be effective novel anesthetics in mice. The authors demonstrate the first use of a high-throughput screen to successfully identify a novel anesthetic chemotype and show mammalian anesthetic activity for members of that chemotype.

Semisynthesis of Intact Complex-Type Triantennary Oligosaccharides from a Biantennary Oligosaccharide Isolated from a Natural Source by Selective Chemical and Enzymatic Glycosylation.

PubMed

Maki, Yuta; Okamoto, Ryo; Izumi, Masayuki; Murase, Takefumi; Kajihara, Yasuhiro

2016-03-16

Attachment of oligosaccharides to proteins is a major post-translational modification. Chemical syntheses of oligosaccharides have contributed to clarifying the functions of these oligosaccharides. However, syntheses of oligosaccharide-linked proteins are still challenging because of their inherent complicated structures, including diverse di- to tetra-antennary forms. We report a highly efficient strategy to access the representative two types of triantennary oligosaccharides through only 9- or 10-step chemical conversions from a biantennary oligosaccharide, which can be isolated in exceptionally homogeneous form from egg yolk. Four benzylidene acetals were successfully introduced to the terminal two galactosides and two core mannosides of the biantennary asialononasaccharide bearing 24 hydroxy groups, followed by protection of the remaining hydroxy groups with acetyl groups. Selective removal of one of the benzylidene acetals gave two types of suitably protected glycosyl acceptors. Glycosylation toward the individual acceptors with protected Gal-β-1,4-GlcN thioglycoside and subsequent deprotection steps successfully yielded two types of complex-type triantennary oligosaccharides.

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

Damian, Luminita, E-mail: luminitadamian@microcal.eu.com; Universite de Toulouse, UPS, IPBS, F-31077 Toulouse; IUB, School of Engineering and Science, D-28727 Bremen

Is single-strand DNA translatable? Since the 60s, the question still remains whether or not DNA could be directly translated into protein. Some discrepancies in the results were reported about functional translation of single-strand DNA but all results converged on a similar behavior of RNA and ssDNA in the initiation step. Isothermal Titration Calorimetry method was used to determine thermodynamic constants of interaction between single-strand DNA and S30 extract of Escherichia coli. Our results showed that the binding was not affected by the nature of the template tested and the dissociation constants were in the same range when ssDNA (K{sub d}more » = 3.62 {+-} 2.1 x 10{sup -8} M) or the RNA corresponding sequence (K{sub d} = 2.7 {+-} 0.82 x 10{sup -8} M) bearing SD/ATG sequences were used. The binding specificity was confirmed by antibiotic interferences which block the initiation complex formation. These results suggest that the limiting step in translation of ssDNA is the elongation process.« less

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…

Multiple dual mode counter-current chromatography with variable duration of alternating phase elution steps.

PubMed

Kostanyan, Artak E; Erastov, Andrey A; Shishilov, Oleg N

2014-06-20

The multiple dual mode (MDM) counter-current chromatography separation processes consist of a succession of two isocratic counter-current steps and are characterized by the shuttle (forward and back) transport of the sample in chromatographic columns. In this paper, the improved MDM method based on variable duration of alternating phase elution steps has been developed and validated. The MDM separation processes with variable duration of phase elution steps are analyzed. Basing on the cell model, analytical solutions are developed for impulse and non-impulse sample loading at the beginning of the column. Using the analytical solutions, a calculation program is presented to facilitate the simulation of MDM with variable duration of phase elution steps, which can be used to select optimal process conditions for the separation of a given feed mixture. Two options of the MDM separation are analyzed: 1 - with one-step solute elution: the separation is conducted so, that the sample is transferred forward and back with upper and lower phases inside the column until the desired separation of the components is reached, and then each individual component elutes entirely within one step; 2 - with multi-step solute elution, when the fractions of individual components are collected in over several steps. It is demonstrated that proper selection of the duration of individual cycles (phase flow times) can greatly increase the separation efficiency of CCC columns. Experiments were carried out using model mixtures of compounds from the GUESSmix with solvent systems hexane/ethyl acetate/methanol/water. The experimental results are compared to the predictions of the theory. A good agreement between theory and experiment has been demonstrated. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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.