Competition in notch signaling with cis enriches cell fate decisions

Notch signaling is involved in cell fate choices during the embryonic development of Metazoa. Commonly, Notch signaling arises from the binding of the Notch receptor to its ligands in adjacent cells driving cell-to-cell communication. Yet, cell-autonomous control of Notch signaling through both ligand-dependent and ligand-independent mechanisms is known to occur as well. Examples include Notch signaling arising in the absence of ligand binding, and cis-inhibition of Notch signaling by titration of the Notch receptor upon binding to its ligands within a single cell. Increasing experimental evidences support that the binding of the Notch receptor with its ligands within a cell (cis-interactions) can also trigger a cell-autonomous Notch signal (cis-signaling), whose potential effects on cell fate decisions and patterning remain poorly understood. To address this question, herein we mathematically and computationally investigate the cell states arising from the combination of cis-signaling with additional Notch signaling sources, which are either cell-autonomous or involve cell-to-cell communication. Our study shows that cis-signaling can switch from driving cis-activation to effectively perform cis-inhibition and identifies under which conditions this switch occurs. This switch relies on the competition between Notch signaling sources, which share the same receptor but differ in their signaling efficiency. We propose that the role of cis-interactions and their signaling on fine-grained patterning and cell fate decisions is dependent on whether they drive cis-inhibition or cis-activation, which could be controlled during development. Specifically, cis-inhibition and not cis-activation facilitates patterning and enriches it by modulating the ratio of cells in the high-ligand expression state, by enabling additional periodic patterns like stripes and by allowing localized patterning highly sensitive to the precursor state and cell-autonomous bistability. Our study exemplifies the complexity of regulations when multiple signalng sources share the same receptor and provides the tools for their characterization.

Potencialidades do dióxido de chumbo eletrodepositado como sensor potenciométrico

This paper proposes an experiment to be performed in both instrumental analysis and experimental physical-chemistry curricular disciplines in order to open options to develop challenging basic research activities. Thus the experimental procedures and the results obtained in the preparation of electrodeposited lead dioxide onto graphite and its evaluation as potentiometric sensor for H3O+ and Pb2+ ions, are presented. The data obtained in acid-base titrations were compared with those of the traditional combination glass electrode at the same conditions. Although a linear sub-Nernstian response to free hydrogen ions was observed for the electrodeposited PbO2 electrode, a good agreement was obtained between them. Working as lead(II) sensing electrode, the PbO2 showed a linear sub-Nernstian behavior at total Pb2+ concentrations ranging from 3,5 x 10-4 to 3,0 x 10-2 mol/L in nitrate media. For the redox couple PbO2/Pb(II) the operational slope converges to the theoretical one, as the acidity of the working solution increases.

Titulador potenciométrico automatizado baseado em sistema de fluxo monossegmentado

A new automated system for acid-base flow titrations is proposed. In the operation mode, several sample to titrant volumetric ratios are injected in an air segmented plug. Five three way solenoid valves and three acrilic junctions, assembled in a hidrodynamic injection system, were accountable for the monosegmented reagents plug formation. A turbulent flow reactor was used for a perfect mix of reagents in the plug. The detector system employed a glass combined electrode fitted in an acrilic holder. Titrations of hydrochloric, nitric and acetic acids, in several concentrations, were performed with standard sodium hidroxide, for evaluation of the efficiency of the system. The relative standard deviation of the determinations was about ±0,5% and each titration was carried out in 3-4 minutes. A Quick BASIC 4.5® program was developed for the titrator control.

Método potenciométrico para determinação de cobre em cachaça

'Cachaça' is the Brazilian name for the spirit obtained from sugarcane. According to Brazilian regulations, it may be sold raw or with addition of sugar and may contain up to 5 mg/L of copper. Copper in "cachaça" was determined by titration with EDTA, using a homemade copper membrane electrode for end-point detection. It was found a pooled standard deviation of 0,057 mg/L and there was no significant difference between the results obtained by the potentiometric method and by flame atomic absorption spectrometry with standard addition. Among the 21 'cachaça' samples from 16 different brands analyzed, three overpassed the legal copper limit. For its characteristics of accuracy, precision, and speed, the potentiometric method may be employed advantageously in routine analysis, specially when low cost is a major concern.

Caracterização ácido-base da superfície de espécies mistas da alga Spirulina através de titulação potenciométrica e modelo de distribuição de sítios discretos

Acid base properties of mixed species of the microalgae Spirulina were studied by potentiometric titration in medium of 0.01 and 0.10 mols L-1 NaNO3 at 25.0±0.10 C using modified Gran functions or nonlinear regression techniques for data fitting. The discrete site distribution model was used, permitting the characterization of five classes of ionizable sites in both ionic media. This fact suggests that the chemical heterogeneity of the ionizable sites on the cell surface plays a major role on the acid-base properties of the suspension in comparison to electrostatic effects due to charge-charge interactions. The total of ionizable sites were 1.75±0.10 and 1.86±0.20 mmolsg-1 in ionic media of 0.01 and 0.10 mols L-1 NaNO3, respectively. A major contribution of carboxylic groups was observed with an average 34 and 22% of ionizable sites being titrated with conditional pcKa of 4.0 and 5.4, respectively. The remaining 44% of ionizable sites were divided in three classes with averaged conditional pcKa of 6.9, 8.7 and 10.12, which may be assigned respectively to imidazolic, aminic, and phenolic functionalities.

Desenvolvimento de um sistema de filtração e titulação para determinação da acidez de ácidos húmicos

The acidity determinations method of humic acids (HA) content was developed by Schnitzer and Gupta and is a very well known procedure. Nevertheless, care is necessary to prevent measure errors due to non-controlled BaCO3 production, during the filtration and titration of HA total acidity. To overcome this problem, we developed in our laboratory a simple filtration and titration system for the determination of HA acidity under inert atmosphere. This system enables a better reproducibility and accuracy of total, carboxylic and phenolic acidity measures than those by Schnitzer and Gupta method.

Avaliação da capacidade tamponante - um experimento participativo

The aim of this work is to show an experiment from which students can learn some of the main characteristics of buffer solutions. A mixture of some acid-base indicators, named as Yamada's indicator, can be used to estimate pH values in an acid-base titration of a buffer, with good approximation. In the experiment it is also possible to verify the relationship between the buffer capacity and the concentrations and the molar ratio of the components of a NH3 / NH4+ buffer solution. The shortage of experiments associated with the relative small importance given to many aspects of buffer solutions, is now explored with simplicity. In the proposed experiments, students prepare buffer solutions by themselves, calculate the pH, understand how acid-base indicators act and learn how buffer solutions work through graph constructed by sharing experimental data.

Studies on formation of chromium niobates

The precise nature of the reaction between chromium chloride and potassium niobate at specific pH levels 12.0, 10.8 and 7.6 has been studied by means of electrometric techniques involving pH and conductometric titrations. The well defined breaks and inflections in the titration curves provide cogent evidence for the formation and precipitation of chromium ortho-Cr2O3.3Nb2 O5, hexa-4Cr2O3.9Nb2 O5 and meta-Cr2O3.3Nb2 O5 niobates in the vicinity of pH 7.5, 6.8 and 5.6, respectively. Analytical investigations of the precipitates have also been carried out which substantiate the results of the electrometric study.

Uma abordagem robusta de cálculo aplicada a um sistema potenciométrico de medida de concentrações hidrogeniônicas em soluções aquosas

The data analyzed in this work were generated following the methodology developed by Molina et al.(J. Electroanal. Chem., 1979) for the calibration of a potentiometric system of measurement of hydrogen-ion concentrations resulting from neutralizations, at 25 ºC, of acidic or alkaline solutions at constant ionic strength (0.1 mol.l-1) held with NaClO4. The observed data present a serious deviation in relation to the mathematical model derived from the Nernst equation, for pH values ranging from 3 to 11, where pH=-log[H+]. We show that the minimization of the sum of the absolute values of the residuals gives estimates that are not influenced by outlying values.

Compostos organolantanídeos contendo o ligante pirazinamida: síntese, caracterização e atividade catalítica na polimerização do etileno

In this work we report the synthesis of some organolanthanide compounds which were identified as LnCl2Cp(PzA)2, Ln = Nd, Sm, Eu and Tb, Cp = cyclopentadienyl and PzA = pirazinamide, by elemental analyses, complexometric titration with EDTA, thermal analyses and IR spectra. Thermal analysis and infrared spectra indicated that the coordination of the pyrazinamide to the lanthanide ions was made by the O atom of the carbonyl group and by one or both N atoms of the pyrazinamide ring. This class of compound showed catalytic activity of ca. 4.0 to 6.4 kgPE molLn-1 h-1 bar-1, in ethylene polymerization, using methylaluminoxane as cocatalyst. The resulting polyethylene presented low crystallinity (20%).

Construção e aplicação de eletrodo de aço inoxidável UNS S31254 como eletrodo indicador em titulações condutimétricas

UNS S31254 SS electrodes have been built to substitute platinum in conductimetric titrations. The electrodes were tested in both acid-basic titration (chloridric acid and sodium hydroxide) and precipitation titration (sodium chloride and argentum nitrate as titrant). The practical application was exemplified from conductimetric tritations of HF ¾ HNO3 mixtures used in metalurgical industry to passivate stainless steels. The results were compared with those obtained using commercial platinum electrodes. The equivalent volumes obtained were comparable within 3% experimental error. Its application depends on the nature of electrolyte. These results have shown that stainless steel, less expensive than platinum (about three order of magnitude), can substitute platinum electrodes in routine analyses and didactic laboratories.

Reaction Kinetics and Viscosity Modelling in the Fusion Syntheses of Ca- and Ca/Mg-resinates

Rosin is a natural product from pine forests and it is used as a raw material in resinate syntheses. Resinates are polyvalent metal salts of rosin acids and especially Ca- and Ca/Mg- resinates find wide application in the printing ink industry. In this thesis, analytical methods were applied to increase general knowledge of resinate chemistry and the reaction kinetics was studied in order to model the non linear solution viscosity increase during resinate syntheses by the fusion method. Solution viscosity in toluene is an important quality factor for resinates to be used in printing inks. The concept of critical resinate concentration, c crit, was introduced to define an abrupt change in viscosity dependence on resinate concentration in the solution. The concept was then used to explain the non-inear solution viscosity increase during resinate syntheses. A semi empirical model with two estimated parameters was derived for the viscosity increase on the basis of apparent reaction kinetics. The model was used to control the viscosity and to predict the total reaction time of the resinate process. The kinetic data from the complex reaction media was obtained by acid value titration and by FTIR spectroscopic analyses using a conventional calibration method to measure the resinate concentration and the concentration of free rosin acids. A multivariate calibration method was successfully applied to make partial least square (PLS) models for monitoring acid value and solution viscosity in both mid-infrared (MIR) and near infrared (NIR) regions during the syntheses. The calibration models can be used for on line resinate process monitoring. In kinetic studies, two main reaction steps were observed during the syntheses. First a fast irreversible resination reaction occurs at 235 °C and then a slow thermal decarboxylation of rosin acids starts to take place at 265 °C. Rosin oil is formed during the decarboxylation reaction step causing significant mass loss as the rosin oil evaporates from the system while the viscosity increases to the target level. The mass balance of the syntheses was determined based on the resinate concentration increase during the decarboxylation reaction step. A mechanistic study of the decarboxylation reaction was based on the observation that resinate molecules are partly solvated by rosin acids during the syntheses. Different decarboxylation mechanisms were proposed for the free and solvating rosin acids. The deduced kinetic model supported the analytical data of the syntheses in a wide resinate concentration region, over a wide range of viscosity values and at different reaction temperatures. In addition, the application of the kinetic model to the modified resinate syntheses gave a good fit. A novel synthesis method with the addition of decarboxylated rosin (i.e. rosin oil) to the reaction mixture was introduced. The conversion of rosin acid to resinate was increased to the level necessary to obtain the target viscosity for the product at 235 °C. Due to a lower reaction temperature than in traditional fusion synthesis at 265 °C, thermal decarboxylation is avoided. As a consequence, the mass yield of the resinate syntheses can be increased from ca. 70% to almost 100% by recycling the added rosin oil.

Determinación de cinc a microescala en un medicamento especifico

This work presents zinc determination in certain medicines that contain zinc oxide and zinc undecylenate. The technique consists of a spectrophotometric micro-scale titration, where EDTA is used as titrant, and xylenol orange as an indicator, in a medium adjusted to pH = 6 with acetic acid and sodium acetate. After each added portion of EDTA, the absorbance value is measured at a selected wavelength, in order to detect the end-point of the spectrophotometric titration. The results already obtained are satisfactory and promote student's interest. An additional contribution intends to propose the use of micro-scale techniques.

Utilização de um eletrodo de grafite-epóxi recoberto com [Zn(FEN)3][tetratris(4-clorofenil) borato]2 sensível a zinco(II) em meio 1,10-fenantrolina como eletrodo indicador em titulações potenciométricas de precipitação

The construction and analytical evaluation of a coated graphite-epoxy electrode sensitive to the zinc-1,10-phenantroline complex based on the [Zn(fen)3][tetrakis(4-chlorophenyl)borate]2 incorporated into a poly(vinylchloride) (PVC) matrix are described. A thin membrane film of this ion-pair, dibutylphthalate (DBPh) and PVC were deposited directly onto an electrically conductive graphite-epoxy support located inside a Perspex® tube. The best PVC polymeric membrane contains 65% (m/m) DBPh, 30% (m/m) PVC and 5% (m/m) of the ion-pair. This electrode shows a response of 19.5 mV dec-1 over the zinc(II) concentration range of 1.0 x 10-5 to 1.0 x 10-3 mol L-1 in 1,10-phenantroline medium, at pH 6.0. The response time was less than 20 seconds and the lifetime of this electrode was more than four months (over 1200 determinations by each polymeric membrane). It was successfully used as an indicator electrode in the potentiometric precipitation titration of zinc(II) ions.

O emprego de quitosana quimicamente modificada com anidrido succínico na adsorção de azul de metileno

The adsorption capacity of alpha-chitosan and its modified form with succinic anhydride was compared with the traditional adsorbent active carbon by using the dye methylene blue, employed in the textile industry. The isotherms for both biopolymers were classified as SSA systems in the Giles model, more specifically in L class and subgroup 3. The dye concentration in the supernatant in the adsorption assay was determined through electronic spectroscopy. By calorimetric titration thermodynamic data of the interaction between methyene blue and the chemically modified chitosan at the solid/liquid interface were obtained. The enthalpy of the dye/chitosan interaction gave 2.47 ± 0.02 kJ mol-1 with an equilibrium constant of 7350 ± 10 and for the carbon/dye interaction this constant gave 5951 ± 8. The spontaneity of these adsorptions are reflected by the free Gibbs energies of -22.1 ± 0.4 and -21.5 ± 0.2 kJ mol-1, respectively, found for these systems. This new adsorbent derived from a natural polysaccharide is as efficient as activated carbon. However 97% of the bonded dye can be eluted by sodium chloride solution, while this same operation elutes only 42% from carbon. Chitosan is efficient in dye removal with the additional advantage of being cheap, non-toxic, biocompatible and biodegradable.