Las mujeres cautivas hispano criollas en la frontera pampeano patagónica y río Cuarto en el período 1736-1879

Desde los tiempos de la conquista en el Río de la Plata, la mujer blanca ha sido prenda de interés para las culturas indígenas. La primera crónica “La Argentina manuscrita”, de Ruy Díaz de Guzmán en el siglo XVII, estaba protagonizada por la cautiva española Lucía Miranda, tomada por la fuerza como esposa por el cacique thimbu Siripo. El despecho del cacique frente al rechazo de Lucía, desencadenó la destrucción del fuerte de Sancti Spiritu.1 En 1798, José de Lavardén pondrá el drama en escena teatral en “Siripo”, nuestra primera obra de teatro nacional.2 El drama de Lucía Miranda, de endeble fundamento histórico, persistió como mito, constituyéndose la cautiva, en un símbolo nacional.

On The Cyclic Bending Behaviour Of A Hard Coating On A Ductile Substrate With Periodic Surface Hardened Regions

A cyclic bending experiment is designed to investigate the interface fracture behaviour of a hard chromium coating on a ductile substrate with periodic surface hardened regions. The unique deflection pattern of the vertical cracks after they run through the coating and impinge at the interface is revealed experimentally. A simple double-layer elastic beam model is adopted to investigate the interfacial shear stresses analytically. A FE model is employed to compute the stresses of the tri-phase structure under a single round of bending, and to investigate the effect of the loading conditions on the deflection pattern of the vertical cracks at the interface. (C) 2008 Elsevier Ltd. All rights reserved.

Modelización de una prueba de afecto hacia la matemática con la teoría de respuesta al ítem

Resumen: Se aplicó el Modelo de Crédito Parcial (MCP) de la Teoría de Respuesta al Ítem (TRI) al análisis de ítems de una escala que mide Afecto hacia la Matemática. Esta variable describe el interés de los estudiantes de Psicología por involucrarse en actividades vinculadas a la matemática y los sentimientos asociados al uso de sus conceptos. La prueba consta de 8 ítems con formato de respuesta Likert de 6 opciones. Participaron 1875 estudiantes de Psicología de la Universidad de Buenos Aires (Argentina) de los cuales un 82% fueron mujeres. El análisis de la consistencia interna brindó un índice altamente satisfactorio (Alfa = .91). Se verificó la condición de unidimensionalidad requerida por el modelo mediante un análisis factorial exploratorio. Todos los análisis basados sobre la TRI se realizaron con el programa Winsteps. La estimación de los parámetros del modelo se efectuó por Máxima Verosimilitud Conjunta. El ajuste del MCP fue satisfactorio para todos los ítems. La Función de Información del Test fue elevada en un rango amplio de niveles del rasgo latente. Un ítem presentó una inversión en dos parámetros de umbral. Como consecuencia, 1 de las 6 categorías del ítem no fue máximamente probable en ningún intervalo de la escala del rasgo latente. Se analizan las implicancias de este hallazgo en la evaluación de la calidad psicométrica del ítem. Los resultados de este estudio permitieron profundizar el análisis del constructo y aportaron evidencias de validez basadas en las estructura interna de la escala

Rapid determination of total CLA concentration in beef fat

[EN]Conjugated linoleic acid (CLA) has many potential healthful properties, and beef is naturally enriched with CLA. Simple and rapid methods to measure total CLA were investigated to enable sorting of beef carcasses with potential enhanced economic value. Direct alcohol extraction combined with measuring absorbance was simple, accurate and perhaps the most viable method for rapid carcass sorting compared to methods using saponification or methylation followed by extraction.

Post-cyclic Strength Degradation of Undisturbed and Remolded Marine Silty Clay

A series of static and cyclic-static tri-axial compression tests under consolidated-undrained conditions are carried out to study the characteristics of post-cyclic strength of the undisturbed and the remolded samples of marine silty clay. It is found that the post-cyclic monotonic strength decreases if the cyclic strain or pore pressure is over a certain value. The maximum degradation is 10% for undisturbed samples while 70% for remolded ones. The relationship between normalized undrained shear strength and apparent overconsolidation ratio, which is determined by the excess pore pressure induced by cyclic loading, is also established. Static consolidated-undrained tests on overconsolidated remolded samples are also performed. It is proposed that the static consolidated-undrained tests may be substituted for the cyclic-static consolidated-undrained tests if the post-cyclic strength degradation of remolded silty clay is needed to be evaluated simply.

Magnitude and Extent of Contaminated Sediment and Toxicity in Chesapeake Bay

INTRODUCTION: This report summarizes the results of NOAA's sediment toxicity, chemistry, and benthic community studies in the Chesapeake Bay estuary. As part of the National Status and Trends (NS&T) Program, NOAA has conducted studies to determine the spatial extent and severity of chemical contamination and associated adverse biological effects in coastal bays and estuaries of the United States since 1991. Sediment contamination in U.S. coastal areas is a major environmental issue because of its potential toxic effects on biological resources and often, indirectly, on human health. Thus, characterizing and delineating areas of sediment contamination and toxicity and demonstrating their effect(s) on benthic living resources are viewed as important goals of coastal resource management. Benthic community studies have a history of use in regional estuarine monitoring programs and have been shown to be an effective indicator for describing the extent and magnitude of pollution impacts in estuarine ecosystems, as well as for assessing the effectiveness of management actions. Chesapeake Bay is the largest estuarine system in the United States. Including tidal tributaries, the Bay has approximately 18,694 km of shoreline (more than the entire US West Coast). The watershed is over 165,000 km2 (64,000 miles2), and includes portions of six states (Delaware, Maryland, New York, Pennsylvania, Virginia, and West Virginia) and the District of Columbia. The population of the watershed exceeds 15 million people. There are 150 rivers and streams in the Chesapeake drainage basin. Within the watershed, five major rivers - the Susquehanna, Potomac, Rappahannock, York and James - provide almost 90% of the freshwater to the Bay. The Bay receives an equal volume of water from the Atlantic Ocean. In the upper Bay and tributaries, sediments are fine-grained silts and clays. Sediments in the middle Bay are mostly made of silts and clays derived from shoreline erosion. In the lower Bay, by contrast, the sediments are sandy. These particles come from shore erosion and inputs from the Atlantic Ocean. The introduction of European-style agriculture and large scale clearing of the watershed produced massive shifts in sediment dynamics of the Bay watershed. As early as the mid 1700s, some navigable rivers were filled in by sediment and sedimentation caused several colonial seaports to become landlocked. Toxic contaminants enter the Bay via atmospheric deposition, dissolved and particulate runoff from the watershed or direct discharge. While contaminants enter the Bay from several sources, sediments accumulate many toxic contaminants and thus reveal the status of input for these constituents. In the watershed, loading estimates indicate that the major sources of contaminants are point sources, stormwater runoff, atmospheric deposition, and spills. Point sources and urban runoff in the Bay proper contribute large quantities of contaminants. Pesticide inputs to the Bay have not been quantified. Baltimore Harbor and the Elizabeth River remain among the most contaminated areas in the Unites States. In the mainstem, deep sediment core analyses indicate that sediment accumulation rates are 2-10 times higher in the northern Bay than in the middle and lower Bay, and that sedimentation rates are 2-10 times higher than before European settlement throughout the Bay (NOAA 1998). The core samples show a decline in selected PAH compounds over the past several decades, but absolute concentrations are still 1 to 2 orders of magnitude above 'pristine' conditions. Core data also indicate that concentrations of PAHs, PCBs and, organochlorine pesticides do not demonstrate consistent trends over 25 years, but remain 10 times lower than sediments in the tributaries. In contrast, tri-butyl-tin (TBT) concentrations in the deep cores have declined significantly since it=s use was severely restricted. (PDF contains 241 pages)

A livelihoods study of fishers and farmers in Thai Nguyen Province

This is the report of a livelihoods study team working together with members of two communes in Quang Tri Province, Vietnam. The study is based on information provided by the commune members, who shared their knowledge and spoke about real problems they face with their livelihoods. The study was conducted from 10-30 October 2001. The team worked with key informants in two communes, Dan Tien in Vo Nhia District and Phuong Tien in Dinh Hoa District, who participated in discussions and represented households in the commune. The livelihoods studies in Dan Tien and Phuong Tien communes explored existing human, labor and natural resources as well as other factors affecting people’s livelihoods. (PDF contains 32 pages)

Proceedings of the Learning Workshop on Livelihoods Analysis. Long An, Vietnam 19-20 November 2002

Sustainable Aquaculture for Poverty Alleviation (SAPA) is a strategy under the overall national program for hunger eradication and poverty reduction. This reflects high attention by the Ministry of Fisheries (MOFI) to the poor. Since the strategy was initiated, several actions have been taken. Recently, conferences and meetings were conducted in Hanoi, Thai Nguyen and Quang Tri. Consequently we also have workshops on a regional basis, and today we are pleased to conduct a workshop in Long An on livelihoods analysis. Now at the Ministry, there are more than 340 projects in aquaculture to attack poverty. The launch of SAPA has been given a high priority among support agencies. Recently Mr Gill of the World Bank and the Ministry agreed that they would act to strengthen aquaculture for poverty reduction. So today with the support of the Long An People’s Committee, NACA and STREAM we have a workshop to strengthen learning about livelihoods analysis. (PDF has 61 pages.)

Biologically-inspired data decorrelation for hyper-spectral imaging

Hyper-spectral data allows the construction of more robust statistical models to sample the material properties than the standard tri-chromatic color representation. However, because of the large dimensionality and complexity of the hyper-spectral data, the extraction of robust features (image descriptors) is not a trivial issue. Thus, to facilitate efficient feature extraction, decorrelation techniques are commonly applied to reduce the dimensionality of the hyper-spectral data with the aim of generating compact and highly discriminative image descriptors. Current methodologies for data decorrelation such as principal component analysis (PCA), linear discriminant analysis (LDA), wavelet decomposition (WD), or band selection methods require complex and subjective training procedures and in addition the compressed spectral information is not directly related to the physical (spectral) characteristics associated with the analyzed materials. The major objective of this article is to introduce and evaluate a new data decorrelation methodology using an approach that closely emulates the human vision. The proposed data decorrelation scheme has been employed to optimally minimize the amount of redundant information contained in the highly correlated hyper-spectral bands and has been comprehensively evaluated in the context of non-ferrous material classification

E-learning y la calibración de ítems de test : teoría de respuesta al ítem versus calibración basada en juicios de expertos. Un estudio jurídico

XVII, 352 p.

Sequence specific recognition and cleavage of DNA by synthetic molecules

DNA recognition is an essential biological process responsible for the regulation of cellular functions including protein synthesis and cell division and is implicated in the mechanism of action of some anticancer drugs. Studies directed towards defining the elements responsible for sequence specific DNA recognition through the study of the interactions of synthetic organic ligands with DNA are described.

DNA recognition by poly-N-methylpyrrolecarboxamides was studied by the synthesis and characterization of a series of molecules where the number of contiguous N-methylpyrrolecarboxamide units was increased from 2 to 9. The effect of this incremental change in structure on DNA recognition has been investigated at base pair resolution using affinity cleaving and MPE•Fe(II) footprinting techniques. These studies led to a quantitative relationship between the number of amides in the molecule and the DNA binding site size. This relationship is called the n + 1 rule and it states that a poly-N methylpyrrolecarboxamide molecule with n amides will bind n + 1 base pairs of DNA. This rule is consistent with a model where the carboxamides of these compounds form three center bridging hydrogen bonds between adjacent base pairs on opposite strands of the helix. The poly-N methylpyrrolecarboxamide recognition element was found to preferentially bind poly dA•poly dT stretches; however, both binding site selection and orientation were found to be affected by flanking sequences. Cleavage of large DNA is also described.

One approach towards the design of molecules that bind large sequences of double helical DNA sequence specifically is to couple DNA binding subunits of similar or diverse base pair specificity. Bis-EDTA-distamycin-fumaramide (BEDF) is an octaamide dimer of two tri-N methylpyrrolecarboxamide subunits linked by fumaramide. DNA recognition by BEDF was compared to P7E, an octaamide molecule containing seven consecutive pyrroles. These two compounds were found to recognize the same sites on pBR322 with approximately the same affinities demonstrating that fumaramide is an effective linking element for Nmethylpyrrolecarboxamide recognition subunits. Further studies involved the synthesis and characterization of a trimer of tetra-N-methylpyrrolecarboxamide subunits linked by β-alanine ((P4)_(3)E). This trimerization produced a molecule which is capable of recognizing 16 base pairs of A•T DNA, more than a turn and a half of the DNA helix.

DNA footprinting is a powerful direct method for determining the binding sites of proteins and small molecules on heterogeneous DNA. It was found that attachment of EDTA•Fe(II) to spermine creates a molecule, SE•Fe(II), which binds and cleaves DNA sequence neutrally. This lack of specificity provides evidence that at the nucleotide level polyamines recognize heterogeneous DNA independent of sequence and allows SE•Fe(II) to be used as a footprinting reagent. SE•Fe(II) was compared with two other small molecule footprinting reagents, EDTA•Fe(II) and MPE•Fe(II).

Fluctuation characteristics of arc voltage and jet flow in a non-transferred dc plasma generated at reduced pressure

A torch with a set of inter-electrode inserts between the cathode and the anode/nozzle with a wide nozzle exit was designed to generate plasma jets at chamber pressures of 500–10 000 Pa. The variation of the arc voltage was examined with the change in working parameters such as gas flow rate and chamber pressure. The fluctuation in the arc voltage was recorded with an oscilloscope, and the plasma jet fluctuation near the torch exit was observed with a high-speed video camera and detected with a double-electrostatic probe. Results show that the 300 Hz wave originated from the tri-phase rectified power supply was always detected under all generating conditions. Helmholtz oscillations over 3000 Hz was detected superposed on the 300 Hz wave at gas flow rates higher than 8.8 slm with a peak to valley amplitude lower than 5% of the average voltage value. No appreciable voltage fluctuation caused by the irregular arc root movement is detected, and mechanisms for the arc voltage and jet flow fluctuations are discussed.

Theoretical studies of novel organic systems : biradicals, polyradicals, and conducting polymers

Chapter 1

Cyclobutanediyl has been studied in both its singlet and triplet states by ab initio electronic structure theory. The triplet, which is the ground state of the molecule, exists in both C_(2h) and C_(2v) forms, which interconvert via a C_s transition state. For the singlet, only a C_(2h) form is found. It passes, via a C_s transition state, onto the C_(2v) surface on which bicyclobutane is the only minimum. The ring-flipping (inversion) process in bicyclobutane includes the singlet biradical as an intermediate, and involves a novel, nonleast motion pathway. Semiclassical periodic orbit theory indicates that the various minima on both the singlet and triplet surfaces can interconvert via quantum mechanical tunneling.

Chapter 2

The dimethylenepolycyclobutadienes (n) are the non-Kekulé analogues of the classical acenes. Application of a variety of theoretical methods reveals several novel features of such structures. Most interesting is the emergence of a parity rule. When n is even, n is predicted to be a singlet, with n disjoint NBMOs. When n is odd, theory predicts a triplet ground state with (n+1) NBMOs that are not fully disjoint.

Chapter 3

Bi(cyclobutadienyl) (2), the cyclobutadiene analogue of biphenyl, and its homologues tri- (3) and tetra(cyclobutadienyl) (4) have been studied using electronic structure theory. Ab initio calculations on 2 reveal that the central bond is a true double bond, and that the structure is best thought of as two allyl radicals plus an ethylene. The singlet and triplet states are essentially degenerate. Trimer 3 is two allyls plus a dimethylenecyclobutanediyl, while 4 is two coplanar bi(cyclobutadienyl) units connected by a single bond. For both 3 and 4, the quintet, triplet, and singlet states are essentially degenerate, indicating that they are tetraradicals. The infinite polymer, polycyclobutadiene, has been studied by HMO, EHCO, and VEH methods. Several geometries based on the structures of 3 and 4 have been studied, and the band structures are quite intriguing. A novel crossing between the valence and conduction bands produces a small band gap and a high density of states at the Fermi level.

Chapter 4

At the level of Hückel theory, polyfulvene has a HOCO-LUCO degeneracy much like that seen in polyacetylene. Higher levels of theory remove the degeneracy, but the band gap (E_g) is predicted to be significantly smaller than analogous structures such as polythiophene and polypyrrole at the fulvenoid geometry. An alternative geometry, which we have termed quinoid, is also conceivable for polyfulvene, and it is predicted to have a much larger E_g. The effects of benzannelation to produce analogues of polyisothianaphthene have been evaluated. We propose a new model for such structures based on conventional orbital mixing arguments. Several of the proposed structures have quite interesting properties, which suggest that they are excellent candidates for conducting polymers.

Chapter 5

Theoretical studies of polydimethylenecyclobutene and polydiisopropylidene- cyclobutene reveal that, because of steric crowding, they cannot achieve a planar, fully conjugated structure in either their undoped or doped states. Rather, the structure consists of essentially orthogonal hexatriene units. Such a structure is incompatible with conventional conduction mechanisms involving polarons and bipolarons.

Análisis y estudio técnico de una instalación industrial para la fabricación de tubos de acero sin costura

[ES]En este trabajo se analiza el proceso de fabricación de tubos de acero sin soldadura en la planta de Tubos Reunido Industrial (en lo sucesivo TRI) en la localidad alavesa de Amurrio. Además, se acompaña el análisis con puntualizaciones sobre las alternativas aplicables en cada paso del proceso y la conveniencia de aplicarlas en la planta estudiada. De esta manera se realiza un estudio de los procesos y equipos requeridos para los distintos pasos que se dan para fabricar tubos de acero sin soldadura de gran calidad a partir de chatarra de acero. Así mismo, dada la importancia de la calidad y el medio ambiente en la estrategia de TRI, se aporta también en este trabajo un resumen de los métodos utilizados en estas áreas.

Structure-, stereochemistry-, and metal-regulated DNA binding/cleaving molecules

In the cell, the binding of proteins to specific sequences of double helical DNA is essential for controlling the processes of protein synthesis (at the level of DNA transcription) and cell proliferation (at the level of DNA replication). In the laboratory, the sequence-specific DNA binding/cleaving properties of restriction endonuclease enzymes (secreted by microorganisms to protect them from foreign DNA molecules) have helped to fuel a revolution in molecular biology. The strength and specificity of a protein:DNA interaction depend upon structural features inherent to the protein and DNA sequences, but it is now appreciated that these features (and therefore protein:DNA complexation) may be altered (regulated) by other protein:DNA complexes, or by environmental factors such as temperature or the presence of specific organic molecules or inorganic ions. It is also now appreciated that molecules much smaller than proteins (including antibiotics of molecular weight less than 2000 and oligonucleotides) can bind to double-helical DNA in sequence-specific fashion. Elucidation of structural motifs and microscopic interactions responsible for the specific molecular recognition of DNA leads to greater understanding of natural processes and provides a basis for the design of novel sequence-specific DNA binding molecules. This thesis describes the synthesis and DNA binding/cleaving characteristics of molecules designed to probe structural, stereochemical, and environmental factors that regulate sequence-specific DNA recognition.

Chapter One introduces the DNA minor groove binding antibiotics Netropsin and Distamycin A, which are di- and tri(N-methylpyrrolecarboxamide) peptides, respectively. The method of DNA affinity cleaving, which has been employed to determine DNA binding properties of designed synthetic molecules is described. The design and synthesis of a series of Netropsin dimers linked in tail-to-tail fashion (by oxalic, malonic, succinic, or fumaric acid), or in head-to-tail fashion (by glycine, β-alanine, and γ-aminobutanoic acid (Gaba)) are presented. These Bis(Netropsin)s were appended with the iron-chelating functionality EDTA in order to make use of the technique of DNA affinity cleaving. Bis(Netropsin)-EDTA compounds are analogs of penta(N-methylpyrrolecarboxamide)-EDTA (P5E), which may be considered a head-to-tail Netropsin dimer linked by Nmethylpyrrolecarboxamide. Low- and high-resolution analysis of pBR322 DNA affinity cleaving by the iron complexes of these molecules indicated that small changes in the length and nature of the linker had significant effects on DNA binding/cleaving efficiency (a measure of DNA binding affinity). DNA binding/cleaving efficiency was found to decrease with changes in the linker in the order β-alanine > succinamide > fumaramide > N-methylpyrrolecarboxamide > malonamide >glycine, γ-aminobutanamide > oxalamide. In general, the Bis(Netropsin)-EDTA:Fe compounds retained the specificity for seven contiguous A:T base pairs characteristic of P5E:Fe binding. However, Bis(Netropsin)Oxalamide- EDTA:Fe exhibited decreased specificity for A:T base pairs, and Bis(Netropsin)-Gaba-EDT A:Fe exhibited some DNA binding sites of less than seven base pairs. Bis(Netropsin)s linked with diacids have C₂-symmmetrical DNA binding subunits and exhibited little DNA binding orientation preference. Bis(Netropsin)s linked with amino acids lack C₂-symmetrical DNA binding subunits and exhibited higher orientation preferences. A model for the high DNA binding orientation preferences observed with head-to-tail DNA minor groove binding molecules is presented.

Chapter Two describes the design, synthesis, and DNA binding properties of a series of chiral molecules: Bis(Netropsin)-EDTA compounds with linkers derived from (R,R)-, (S,S)-, and (RS,SR)-tartaric acids, (R,R)-, (S,S)-, and (RS,SR)-tartaric acid acetonides, (R)- and (S)-malic acids, N ,N-dimethylaminoaspartic acid, and (R)- and (S)-alanine, as well as three constitutional isomers in which an N-methylpyrrolecarboxamide (P1) subunit and a tri(N-methylpyrrolecarboxamide)-EDTA (P3-EDTA) subunit were linked by succinic acid, (R ,R)-, and (S ,S)-tartaric acids. DNA binding/cleaving efficiencies among this series of molecules and the Bis(Netropsin)s described in Chapter One were found to decrease with changes in the linker in the order β-alanine > succinamide > P1-succinamide-P3 > fumaramide > (S)-malicamide > N-methylpyrrolecarboxamide > (R)-malicamide > malonamide > N ,N-dimethylaminoaspanamide > glycine = Gaba = (S,S)-tartaramide = P1-(S,S)-tanaramide-P3 > oxalamide > (RS,SR)-tartaramide = P1- (R,R)-tanaramide-P3 > (R,R)-tartaramide (no sequence-specific DNA binding was detected for Bis(Netropsin)s linked by (R)- or (S)-alanine or by tartaric acid acetonides). The chiral molecules retained DNA binding specificity for seven contiguous A:T base pairs. From the DNA affinity cleaving data it could be determined that: 1) Addition of one or two substituents to the linker of Bis(Netropsin)-Succinamide resulted in stepwise decreases in DNA binding affinity; 2) molecules with single hydroxyl substituents bound DNA more strongly than molecules with single dimethylamino substituents; 3) hydroxyl-substituted molecules of (S) configuration bound more strongly to DNA than molecules of (R) configuration. This stereochemical regulation of DNA binding is proposed to arise from the inherent right-handed twist of (S)-enantiomeric Bis(Netropsin)s versus the inherent lefthanded twist of (R)-enantiomeric Bis(Netropsin)s, which makes the (S)-enantiomers more complementary to the right-handed twist of B form DNA.

Chapter Three describes the design and synthesis of molecules for the study of metalloregulated DNA binding phenomena. Among a series of Bis(Netropsin)-EDTA compounds linked by homologous tethers bearing four, five, or six oxygen atoms, the Bis(Netropsin) linked by a pentaether tether exhibited strongly enhanced DNA binding/cleaving in the presence of strontium or barium cations. The observed metallospecificity was consistent with the known affinities of metal cations for the cyclic hexaether 18-crown-6 in water. High-resolution DNA affinity cleaving analysis indicated that DNA binding by this molecule in the presence of strontium or barium was not only stronger but of different sequence-specificity than the (weak) binding observed in the absence of metal cations. The metalloregulated binding sites were consistent with A:T binding by the Netropsin subunits and G:C binding by a strontium or barium:pentaether complex. A model for the observed positive metalloregulation and novel sequence-specificity is presented. The effects of 44 different cations on DNA affinity cleaving by P5E:Fe were examined. A series of Bis(Netropsin)-EDTA compounds linked by tethers bearing two, three, four, or five amino groups was also synthesized. These molecules exhibited strong and specific binding to A:T rich regions of DNA. It was found that the iron complexes of these molecules bound and cleaved DNA most efficiently at pH 6.0-6.5, while P5E:Fe bound and cleaved most efficiently at pH 7.5-8.0. Incubating the Bis(Netropsin) Polyamine-EDTA:Fe molecules with K₂PdCl₄ abolished their DNA binding/cleaving activity. It is proposed that the observed negative metalloregulation arises from kinetically inert Bis(Netropsin) Polyamine:Pd(II) complexes or aggregates, which are sterically unsuitable for DNA complexation. Finally, attempts to produce a synthetic metalloregulated DNA binding protein are described. For this study, five derivatives of a synthetic 52 amino acid residue DNA binding/cleaving protein were produced. The synthetic mutant proteins carried a novel pentaether ionophoric amino acid residue at different positions within the primary sequence. The proteins did not exhibit significant DNA binding/cleaving activity, but they served to illustrate the potential for introducing novel amino acid residues within DNA binding protein sequences, and for the development of the tricyclohexyl ester of EDTA as a superior reagent for the introduction of EDT A into synthetic proteins.

Chapter Four describes the discovery and characterization of a new DNA binding/cleaving agent, [SalenMn(III)]OAc. This metal complex produces single- and double-strand cleavage of DNA, with specificity for A:T rich regions, in the presence of oxygen atom donors such as iodosyl benzene, hydrogen peroxide, or peracids. Maximal cleavage by [SalenMn(III)]OAc was produced at pH 6-7. A comparison of DNA singleand double-strand cleavage by [SalenMn(III)]⁺ and other small molecules (Methidiumpropyl-EDTA:Fe, Distamycin-EDTA:Fe, Neocarzinostatin, Bleomycin:Fe) is presented. It was found that DNA cleavage by [SalenMn(III)]⁺ did not require the presence of dioxygen, and that base treatment of DNA subsequent to cleavage by [SalenMn(III)]⁺ afforded greater cleavage and alterations in the cleavage patterns. Analysis of DNA products formed upon DNA cleavage by [SalenMn(III)] indicated that cleavage was due to oxidation of the sugar-phosphate backbone of DNA. Several mechanisms consistent with the observed products and reaction requirements are discussed.

Chapter Five describes progress on some additional studies. In one study, the DNA binding/cleaving specificities of Distamycin-EDTA derivatives bearing pyrrole N-isopropyl substituents were found to be the same as those of derivatives bearing pyrrole N-methyl substituents. In a second study, the design of and synthetic progress towards a series of nucleopeptide activators of transcription are presented. Five synthetic plasmids designed to test for activation of in vitro run-off transcription by DNA triple helix-forming oligonucleotides or nucleopeptides are described.

Chapter Six contains the experimental documentation of the thesis work.