Paper partition chromatographic study of the products of the chlorine oxidation of D-glucose and Methyl-beta-D-glucoside at pH "0" and pH 4.6

Thesis (M.A.)--Boston UniversityD-Glucose and methyl-beta-D-glucoside were oxidized at pH "0" by continuously passing chlorine gas into aqueous solutions of carbohydrates for fourteen days at room temperature. The products of these oxidations were investigated after lyophilization of the reaction mixtures by paper partition chromatographic analysis with the solvent system n-butanol-acetic acid-water, 4: 1: 5, and using various spray reagents. These two carbohydrates, D-glucose and methyl-beta-D-glucoside, were also oxidized for twenty-four hours with chlorine water at pH 4.6 in 0.3 molar acetate buffer at 35.7°C. A large excess of carbohydrate with respect to oxidant was used in these oxidations. The results obtained are listed in Table XXVI. D-Glucaric and 2-ketogluconic acids were shown not to present these oxidations even though their presence were reported by other investigators using similar oxidation procedures (21,35a). The conditions of the oxidation of methyl-beta-D-glucoside at pH 4.6 were shown to be too mild to produce oxidative changes, in contradiction to the work of Henderson (35a) who, using similar oxidative conditions, reported that the glucoside underwent oxidation to produce a number of oxidation products. No temperature dependence of Rf or Rg was noted, even though such temperature dependence was previously reported. A large excess of D-glucose was shown not to affect the Rf values of compounds present in smaller quantities. A method was devised whereby an acidic or alkaline compound and a reducing compound may be detected on a single chromatogram: the so-called "double spraying" technique. It was shown experimentally that carbohydrates and sugar acids are not affected by storage in water solution under refrigeration for periods of over six months. The presence of sodium acetate and an acidic impurity in the sodium acetate used were shown on chromatograms of the oxidation experiments carried out in acetate buffers. Recent advances in the chemistry of the halogen oxidation of carbohydrates are reported

Ionization and dissociation equilibria in sulfur dioxide solution. Part 1: dissociation of ion pairs. Part II: equilibria of meta phenyl derivatives of trityl chloride. Part III: the apparent ionization of hexaphenylethane

Thesis (Ph.D.)--Boston UniversityPart I Dissociation of Ion Pairs. The conductivity of potassium chloride, bromide and iodide and of tetramethylammonium bromide were measured over a dilution range of 10^2 to 10^5 liters per mole in liquid sulfur dioxide solution at 0.12°C. and at -8.93°C. employing the internal dilution technique described by Lichtin and Glazer. Similar measurements were carried out on tetramethylammonium sulfate at 0.12°C. Equilibrium constants were evaluated from these data by the method of Shedlovsky. The method of least mean squares was applied to establish the best straight line representing the Shedlovsky equation for each compound at each temperature. The experimental data and calculations presented in this dissertation clearly demonstrate that the theory of ionic association of Bjerrum is an accurate representation of the behavior of 1-1 electrolytes in liquid sulfur dioxide solution. The distance of closest approach of the ions were calculated from the experimental equilibrium constants by the Bjerrum equation. Values obtained from the data on pure ionic compounds in sulfur dioxide solution are in excellent agreement (± 0.1Å) with the sums of crystallographic radii of the corresponding ions. Conversely, ion pair dissoc:iation constants calculated from crystal radii agree closely with the experimental values obtained in this research. In the case of tetramethylammonium bromide, where a crystallographic radius is not available for the cation, a value estimated as the largest Van der Waals radius from the center of the molecule by direct measurement of a Fisher-Herschfelder-Taylor model gave excellent agreement with experiment. An equation for ΔH° derived solely from the Bjerrum theory gave values which were in good agreement within the uncertainties inherent in the experimental values of this property. On the basis of these observations it is possible to conclude that the Bjerrum treatment is quantitatively exact for 1-1 electrolytes in sulfur dioxide solution. This is the first demonstration of quantitative adherence to this theory. Part II Equilibria of m-Phenyl Derivatives of Trityl Chloride. All attempts to utilize conductivity data for ring substituted derivatives of triphenylchloromethane in sulfur dioxide solutions for the direct estimation of the electronic influence of the ring substituents have, in the past, met with little quantitative success due to the complications arising from short range ionic interactions which give rise to ion pairs and higher aggregates in solvents of low dielectric constant. In a qualitative manner Lichtin and Bartlett were able to demonstrate that ionic association equilibria introduce only minor errors in the relative equilibrium constants for trityl chloride and those ring substituted derivatives which are weaker electrolytes than trityl chloride. In this way these workers were able to estimate the qualitative electronic influences of those substituents which stabilize triphenylchloromethane more than they stabilize the triphenyl carbonium ion in sulfur dioxide solution. Since, however, many theoretically interesting substituents exert an effect resulting in an enhanced ionization of triphenylchloromethane it is both interesting and valuable to develop a method of evaluating an ion pair correction term to be used with the experimental data for these compounds. A method is proposed for the quantitative evaluation of an ion pair correction term to be applied to experimental conductivity data for ring substituted trityl chlorides in sulfur dioxide solution. With this method it is now possible to obtain a quantitative measure of the electronic influence of substituents from conductivity data in this solvent. The assumptions involved in this treatment are as follows: (1) The Bjerrum equation is an exact representation of ionic association behavior of 1-1 electrolytes in this solvent. This assumption is supported by the evidence presented in Part I. (2) The triarylmethyl carbonium ion in solution presents a spherical appearance to the anion by virtue of a tumbling motion about its center of gravity. The ion sweeps out an effective volume equal to a sphere whose radius is the largest Van der Waals radius from the center of gravity of the ion. (3) The Bjerrum radius of the triarylcarbonium ion is equal to the radius of the swept out volume and can be estimated directly from molecular models as being the largest Van der Waals distance from the center of gravity. Experimental equilibrium constants were determined by applying the Shedlovsky and least mean squares method to the conductivity data for mono-,di-, and tri-m-phenyl derivatives of trityl chloride in liquid sulfur dioxide at 0.12°C. and -8.93°C. obtained in this research. These values combined with calculated ion pair dissociation constants permitted the calculation of the experimentally inaccessible ionization constants for these compounds. It was demonstrated that the influence of stepwise introduction of m-phenyl substituents on the calculated free energy of ionization of the corresponding trityl chlorides could be described by equal free energy increments for each successive substitution. A sigma constant for the m-phenyl group was determined from acid strength measurements on benzoic and m-phenyl benzoic acids. With this value it was possible to calculate a Hammett rho parameter for the ionization of trityl chlorides in sulfur dioxide solution. Resonance sigma constants were calculated for p-phenyl, p-methyl and p-t-butyl groups. Hammett correlation plots were constructed for the ionization reaction in sulfur dioxide employing all available experimental data from this research and from the literature. It was found that poor correlations could be obtained with experimental dissociation constants while, on the other hand excellent agreement resulted when ionization constants calculated on the basis of the ion pair treatment were employed. An electron supplying resonance sigma for the para phenyl group of -0.148 is proposed. Values of -0.3 have been calculated for both the p-methyl and p-t-butyl group. This research has provided a useful tool for evaluation of substituent effects. Part III The Apparent Ionization of Hexaphenylethane. The conductivity which has been observed with solutions of hexaphenylethane in liquid sulfur dioxide has been subject to several chemical interpretations which differ in detail but which all assume an ionization mechanism involving only hexaphenylethane and sulfur dioxide. This conductivity is now found to be an artifact of at least two processes, namely, reaction with dissolved oxygen and a photochemical transformation. Experiments employing crystalline samples of ethane of purity established by quantitative oxygenation and a refinement of the conductivity technique of Lichtin and Glazer reveal a lack of reproducibility like that apparent in older work. Although irradiation with a Burton ultraviolet lamp produces slow but large increases in conductivity, variable exposure to light cannot be the sole source of the discrepancies since consistent data do not result from experiments performed in the dark. The fact that increasingly efficient degassing of the solvent prior to dissolution leads to progressive diminution of the conductivity suggests production of an electrolyte by reaction with a gaseous impurity. This reagent has been identified as oxygen. The conductivity of an oxygenated solution of hexaphenylethane is somewhat greater than the highest comparable values obtained without degassing the solvent. The conductivity of this solution does not change upon irradiation whereas that of the solutions in degassed sulfur dioxide increases

Newsblaster Russian-English Clustering Performance Analysis

The Natural Language Group is developing a multi-language version of Columbia Newsblaster, a program that generates summaries of news articles collected from web sites. Newsblaster currently processes articles in Arabic, Japanese,Portuguese, Spanish, and Russian, as well as English. This report outlines the Russian language processing software,focusing on machine translation and document clustering. Russian-English clustering results are analyzed and indicate encouraging inter-language and intra-language performance

Iron imaging reveals tumor and metastasis macrophage hemosiderin deposits in breast cancer.

Iron-deposition is a metabolic biomarker of macrophages in both normal and pathological situations, but the presence of iron in tumor and metastasis-associated macrophages is not known. Here we mapped and quantified hemosiderin-laden macrophage (HLM) deposits in murine models of metastatic breast cancer using iron and macrophage histology, and in vivo MRI. Iron MRI detected high-iron pixel clusters in mammary tumors, lung metastasis, and brain metastasis as well as liver and spleen tissue known to contain the HLMs. Iron histology showed these regions to contain clustered macrophages identified by their common iron status and tissue-intrinsic association with other phenotypic macrophage markers. The in vivo MRI and ex vivo histological images were further processed to determine the frequencies and sizes of the iron deposits, and measure the number of HLMs in each deposit to estimate the in vivo MRI sensitivity for these cells. Hemosiderin accumulation is a macrophage biomarker and intrinsic contrast source for cellular MRI associated with the innate function of macrophages in iron metabolism systemically, and in metastatic cancer

Solar activity prediction

A statistical study of formulas for predicting the sunspot number several years in advance is reported. By using a data lineup with cycle maxima coinciding, and by using multiple and nonlinear predictors, a new formula which gives better error estimates than former formulas derived from the work of McNish and Lincoln is obtained. A statistical analysis is conducted to determine which of several mathematical expressions best describes the relationship between 10.7 cm solar flux and Zurich sunspot numbers. Attention is given to the autocorrelation of the observations, and confidence intervals for the derived relationships are presented. The accuracy of predicting a value of 10.7 cm solar flux from a predicted sunspot number is dicussed

Imaging endogenous macrophage iron deposits reveals a metabolic biomarker of polarized tumor macrophage infiltration and response to CSF1R breast cancer immunotherapy.

Iron deposits are a phenotypic trait of tumor-associated macrophages (TAMs). Histological iron imaging and contrast-agent free magnetic resonance imaging (MRI) can detect these deposits, but their presence  in human cancer, and correlation with immunotherapeutic response is largely untested. Here, primarily using these iron imaging approaches, we evaluated the spatial distribution of polarized macrophage populations containing high endogenous levels of iron in preclinical murine models and human breast cancer, and used them as metabolic biomarkers to correlate TAM infiltration with response to immunotherapy in preclinical trials. Macrophage-targeted inhibition of the colony stimulating factor 1 receptor (CSF1R) by immunotherapy was confirmed to inhibit macrophage accumulation and slow mammary tumor growth in mouse models while also reducing hemosiderin iron-laden TAM accumulation as measured by both iron histology and in vivo iron MRI (FeMRI). Spatial profiling of TAM iron deposit infiltration defined regions of maximal accumulation and response to the CSF1R inhibitor, and revealed differences between microenvironments of human cancer according to levels of polarized macrophage iron accumulation in stromal margins. We therefore demonstrate that iron deposition serves as an endogenous metabolic imaging biomarker of TAM infiltration in breast cancer that has high translational potential for evaluation of immunotherapeutic response

Nuclear magnetic resonance probes of membrane biophysics: Structure and dynamics

The phospholipid membrane is a self-assembled, dynamic molecular system that may exist alone in association with only water, or in complex systems comprised of multiple lipid types and proteins. In this dissertation the intra- and inter-molecular forces responsible for the atomistic, molecular and collective equilibrium structure and dynamics are studied by nuclear magnetic resonance spectroscopy (NMR). The multinuclear NMR measurements and various experimental techniques are able to provide data that enable the characterization of the hierarchical spatio-temporal organization of the phospholipid membrane. The experimental and theoretical studies conducted target membrane interactions ranging from model systems composed of only water and lipids, to multiple component domain forming membranes that are in association with peripheral and trans-membrane proteins. These measurements consisit of frequency spectrum lineshapes and nuclear-spin relaxation rates obtained using 2 H NMR, 13 C NMR, 31 P NMR and 1 H NMR. The changes of these experimental observables are interpreted within a statistical thermodynamic framework that allows the membrane structure, activation energies, and correlation times of motion to be determined. The cases presented demonstrate how fundamental principles of NMR spectroscopy may be applied to a host of membranes, leading to the biophysical characterization of membrane structure and dynamics