398 resultados para Agglomerate Breakage


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The interpretation of data on genetic variation with regard to the relative roles of different evolutionary factors that produce and maintain genetic variation depends critically on our assumptions concerning effective population size and the level of migration between neighboring populations. In humans, recent population growth and movements of specific ethnic groups across wide geographic areas mean that any theory based on assumptions of constant population size and absence of substructure is generally untenable. We examine the effects of population subdivision on the pattern of protein genetic variation in a total sample drawn from an artificial agglomerate of 12 tribal populations of Central and South America, analyzing the pooled sample as though it were a single population. Several striking findings emerge. (1) Mean heterozygosity is not sensitive to agglomeration, but the number of different alleles (allele count) is inflated, relative to neutral mutation/drift/equilibrium expectation. (2) The inflation is most serious for rare alleles, especially those which originally occurred as tribally restricted "private" polymorphisms. (3) The degree of inflation is an increasing function of both the number of populations encompassed by the sample and of the genetic divergence among them. (4) Treating an agglomerated population as though it were a panmictic unit of long standing can lead to serious biases in estimates of mutation rates, selection pressures, and effective population sizes. Current DNA studies indicate the presence of numerous genetic variants in human populations. The findings and conclusions of this paper are all fully applicable to the study of genetic variation at the DNA level as well.

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Colorectal cancer is a complex disease that is thought to arise when cells accumulate mutations that allow for uncontrolled growth. There are several recognized mechanisms for generating such mutations in sporadic colon cancer; one of which is chromosomal instability (CIN). One hypothesized driver of CIN in cancer is the improper repair of dysfunctional telomeres. Telomeres comprise the linear ends of chromosomes and play a dual role in cancer. Its length is maintained by the ribonucleoprotein, telomerase, which is not a normally expressed in somatic cells and as cells divide, telomeres continuously shorten. Critically shortened telomeres are considered dysfunctional as they are recognized as sites of DNA damage and cells respond by entering into replicative senescence or apoptosis, a process that is p53-dependent and the mechanism for telomere-induced tumor suppression. Loss of this checkpoint and improper repair of dysfunctional telomeres can initiate a cycle of fusion, bridge and breakage that can lead to chromosomal changes and genomic instability, a process that can lead to transformation of normal cells to cancer cells. Mouse models of telomere dysfunction are currently based on knocking out the telomerase protein or RNA component; however, the naturally long telomeres of mice require multiple generational crosses of telomerase null mice to achieve critically short telomeres. Shelterin is a complex of six core proteins that bind to telomeres specifically. Pot1a is a highly conserved member of this complex that specifically binds to the telomeric single-stranded 3’ G-rich overhang. Previous work in our lab has shown that Pot1a is essential for chromosomal end protection as deletion of Pot1a in murine embryonic fibroblasts (MEFs) leads to open telomere ends that initiate a DNA damage response mediated by ATR, resulting in p53-dependent cellular senescence. Loss of Pot1a in the background of p53 deficiency results in increased aberrant homologous recombination at telomeres and elevated genomic instability, which allows Pot1a-/-, p53-/- MEFs to form tumors when injected into SCID mice. These phenotypes are similar to those seen in cells with critically shortened telomeres. In this work, we created a mouse model of telomere ysfunction in the gastrointestinal tract through the conditional deletion of Pot1a that recapitulates the microscopic features seen in severe telomere attrition. Combined intestinal loss of Pot1a and p53 lead to formation of invasive adenocarcinomas in the small and large intestines. The tumors formed with long latency, low multiplicity and had complex genomes due to chromosomal instability, features similar to those seen in sporadic human colorectal cancers. Taken together, we have developed a novel mouse model of intestinal tumorigenesis based on genomic instability driven by telomere dysfunction.

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We have performed microfluidic experiments with erythrocytes passing through a network of microchannels of 20–25 μm width and 5 μm of height. Red blood cells (RBCs) were flowing in countercurrent directions through microchannels connected by μm pores. Thereby, we have observed interesting flow dynamics. All pores were blocked by erythrocytes. Some erythrocytes have passed through pores, depending on the channel size and cell elasticity. Many RBCs split into two or more smaller parts. Two types of splits were observed. In one type, the lipid bilayer and spectrin network were cut at the same time. In the second type, the lipid bilayer reconnected, but the part of spectrin network stayed outside the cell forming a rope like structure, which could eventually break. The microporous membrane results in multiple breakups of the cells, which can have various clinical implications, e.g., glomerulus hematuria and anemia of patients undergoing dialysis. The cell breakup procedure is similar to the one observed in the droplet breakage of viscoelastic liquids in confinement.

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A retrospective evaluation of glass ionomer cement (GIC) in middle ear surgery with emphasis on short- and long-term safety was conducted at the tertiary referral center. GIC was applied between 1995 and 2006 in 444 patients in otologic surgery. Technical aspects, safety, benefits and complications due to GIC were analysed until 2011 (follow-up 5-16 years; mean 10 years). GIC was applied in stapes surgery (228 primary, 92 revisions), cochlear implants (108) and implantable hearing aids (7), ossiculoplasty (7), for coverage of opened mastoid air cells towards the external ear canal (1) and inner ear fistula closure (1). GIC turned out to be very handy in stapes surgery for optimal prosthesis fixation at the incus (260) and on the malleus handle (60) without complications. Results suggest that GIC may diminish the danger of incus necrosis in primary stapedotomy. In cochlear implants and implantable hearing aids, GIC was used for casing alone (74), casing and electrode fixation (27) and electrode alone fixation (14). Inflammatory reactions were observed in five cases (4.3 %), mostly after trauma. Broken cement fragments appeared to promote foreign body rejection. In seven cases an incudo-stapedial gap was repaired with GIC with excellent hearing gain; in three cases (43 %) revision surgery was needed due to cement breakage. In one case, GIC was applied for a watertight coverage of opened mastoid cells, and in the other for fistula closure of the lateral semi-circular canal over cartilage, covered with bone pathé; follow-up was uneventful. Targeted use of GIC in middle ear surgery rarely poses problems. GIC cannot be used in neuro-otosurgery in contact with cerebrospinal fluid because of possible aluminium encephalopathy.

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STUDY DESIGN Retrospective analysis of prospectively collected clinical data. OBJECTIVE To assess the long-term outcome of patients with monosegmental L4/5 degenerative spondylolisthesis treated with the dynamic Dynesys device. SUMMARY OF BACKGROUND DATA The Dynesys system has been used as a semirigid, lumbar dorsal pedicular stabilization device since 1994. Good short-term results have been reported, but little is known about the long-term outcome after treatment for degenerative spondylolisthesis at the L4/5 level. METHODS A total of 39 consecutive patients with symptomatic degenerative lumbar spondylolisthesis at the L4/5 level were treated with bilateral decompression and Dynesys instrumentation. At a mean follow-up of 7.2 years (range, 5.0-11.2 y), they underwent clinical and radiographic evaluation and quality of life assessment. RESULTS At final follow-up, back pain improved in 89% and leg pain improved in 86% of patients compared with preoperative status. Eighty-three percent of patients reported global subjective improvement. Ninety-two percent would undergo the surgery again. Eight patients (21%) required further surgery because of symptomatic adjacent segment disease (6 cases), late-onset infection (1 case), and screw breakage (1 case). In 9 cases, radiologic progression of spondylolisthesis at the operated segment was found. Seventy-four percent of operated segments showed limited flexion-extension range of <4 degrees. Adjacent segment pathology, although without clinical correlation, was diagnosed at the L5/S1 (17.9%) and L3/4 (28.2%) segments. In 4 cases, asymptomatic screw loosening was observed. CONCLUSIONS Monosegmental Dynesys instrumentation of degenerative spondylolisthesis at L4/5 shows good long-term results. The rate of secondary surgeries is comparable to other dorsal instrumentation devices. Residual range of motion in the stabilized segment is reduced, and the rate of radiologic and symptomatic adjacent segment degeneration is low. Patient satisfaction is high. Dynesys stabilization of symptomatic L4/5 degenerative spondylolisthesis is a possible alternative to other stabilization devices.

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The DNA breakage effect of the anticancer agent 3,6-diaziridinyl-2,5-bis(carboethoxyamino)-1,4-benzoquinone (AZQ, NSC-182986) on bacteriophage PM2 DNA was investigated using agarose gel electrophoresis. AZQ caused both single-stranded and double-stranded breaks after reduction with NaBH(,4), but it was not active in the native state. At 120 (mu)M, it degraded 50% of the closed circular form I DNA into 40% form II DNA (single-stranded break) and 10% form III DNA (double-stranded break). It produced a dose-response breakage between 1 (mu)M and 320 (mu)M. The DNA breakage exhibited a marked pH dependency. At 320 (mu)M, AZQ degraded 80% and 60% of form I DNA at pH 4 and 10 respectively, but none between pH 6 to 8. The DNA breakage at physiologic pH was greatly enhanced when 10 (mu)M cupric sulfate was included in the incubation mixture. The DNA strand scission was inhibited by catalase, glutathione, KI, histidine, Tiron, and DABCO. These results suggest that the DNA breakage may be caused by active oxygen metabolites including hydroxyl free radical. The bifunctional cross-linking activity of reduced AZQ on isolated calf thymus DNA was investigated by ethidium fluorescence assay. The cross-linking activity exhibited a similar pH dependency; highest in acidic and alkaline pH, inactive under neutral conditions. Using the alkaline elution method, we found that AZQ induced DNA single-stranded breaks in Chinese hamster ovary cells treated with 50 (mu)M of AZQ for 2 hr. The single-stranded break frequencies in rad equivalents were 17 with 50 (mu)M and 140 with 100 (mu)M of AZQ. In comparison, DNA cross-links appeared in cells treated with only 1 to 25 (mu)M of AZQ for 2 hr. The cross-linking frequencies in rad equivalents were 39 and 90 for 1 and 5 (mu)M of AZQ, respectively. Both DNA-DNA and DNa-protein cross-links were induced by AZQ in CHO cells as revealed by the proteinas K digestion assay. DNA cross-links increased within the first 4 hr of incubation in drug-free medium and slightly decreased by 12 hr, and most of the cross-links disappeared after cells were allowed to recovered for 24 hr.^ By electrochemical analysis, we found that AZQ was more readily reduced at acidic pH. However, incubation of AZQ with NaBH(,4) at pH 7.8 or 10, but not at 4, produced superoxide anion. The opening of the aziridinyl rings of AZQ at pH 4 was faster in the presence of NaBH(,4) than in its absence; no ring-opening was detected at pH 7.8 regardless of the inclusion of NaBH(,4). . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI ^

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Human a2 -macroglobulin ( a2 M; homotetramer, Mr 720 kDa) is an essential scavenger of proteinases in the serum. Each of its four subunits has a ‘bait region’, with cleavage sequences for almost all endo-proteinases, an unusual thiol ester moiety and a receptor-binding domain (RBD). Bait region cleavage in native a2 M ( a2 M-N) by a proteinase results in rapid thiol ester breakage, with a large-scale structural transformation, in which a2 M uniquely entraps the proteinase in a cage-like structure and exposes receptor-binding domains for rapid endocytosis. Transformed a2 M ( a2 M-TR) contains up to two proteinases, which remain active to small substrates. 3-D electron microscopy is optimally suited to study this unusual structural change at resolutions near (1/30) Å−1. ^ The structural importance of the thiol esters was demonstrated by a genetically-engineered a2 M, with the cysteines involved in thiol ester formation mutated to serines, which appeared structurally homologous to a2 M-TR. This demonstrates that the four highly labile thiol esters alone maintain the a2 M-N structure, while the ‘closed trap’ formed by a2 M-TR is a more stable structural form. ^ Half-transformed a2 M ( a2 M-HT), with cleaved bait regions and thiol esters in only two of its four subunits, provides an important structural link between a2 M-N and a2 M-TR. A comparison with a2 M-N showed the two proteinase-entrapping domains were above and below the plane bisecting the long axis. Both a2 M-N and a2 M-TR consist of two dense, oppositely twisted strands with significant interconnections, indicating that the structural change involves a rotation of these strands. In a2 M-HT these strands were partially untwisted with large central openings, revealing the manner in which the proteinase enters the internal cavity of a2 M. ^ In reconstructions of a2 M-N, a2 M-HT and a2 M-TR labeled with a monoclonal Fab, the Fabs were located on distal ends of each constitutive strand, demonstrating an anti-parallel arrangement of the subunits. Separation between the top and bottom pairs of Fabs was nearly the same on all structures, but the pairs were rotated about the long axis. Taken together, these results indicate that upon proteinase cleavage the two strands in a2 M-N separate. The proteinase enters the structure, while the strands re-twist to encage it. In a2 M-TR, which displays receptor-binding arms, more than two subunits are transformed as strands in the transformed half of a2 M-HT were not separated. ^

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This study has evaluated the utility of measuring effects of low level occupational exposure of nursing personnel to antineoplastic agents. The effect measured in this study is chromosomal damage in peripheral lymphocytes (chromosomal breakage and micronuclei frequency).^ Using nursing personnel in three exposure classifications (low, moderate and high) and breast cancer patients before and after treatment with antineoplastic agents, a weak but statistically significant association was found between exposure and chromosomal damage. Of special interest was the finding that consistent glove usage was negatively associated with increased chromosomal damage.^ The study also demonstrated a statistically significant association between the two measures of chromosomal damage: chromosomal breakage and micronuclei frequency. This suggests that the micronucleus method is a useful test for studying cytogenetic effects in lymphocytes. ^

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The clinical application of chemopreventive agents is expected to prevent the appearance of cancer by arresting carcinogenesis or reversing it in the precancerous stages. The hypothesis of the present investigations was that chemopreventive agents (retinoids and antioxidant vitamins) may counteract the clastogenic effects of bleomycin in vitro in both lymphoblastoid cell lines and primary lymphocyte cultures and that a similar phenomenon can be detected in lymphocytes from individuals treated with 13-cis-retinoic acid. The efficacy of 13-cis-retinoic acid, n-(4-hydroxyphenyl)-retinamide, ascorbic acid, n-acetyl-l-cysteine, alpha-tocopherol, and alpha-tocopherol-acid succinate was tested against bleomycin-induced chromosomal breakage.^ The results provided direct evidence of the concentration-related protective effects of these agents against bleomycin-induced clastogenicity in cultures of human lymphoblastoid cell lines in vitro. Similar anticlastogenic protection was demonstrated with 13-cis-retinoic acid, ascorbic acid, n-acetyl-l-cysteine, and alpha-tocopherol-acid succinate in primary lymphocyte cultures in vitro. The in vitro anticlastogenic effect of 13-cis-retinoic acid was also demonstrated in lymphocyte cultures from peripheral blood samples from patients treated with this retinoid.^ An important consideration is that the concentrations used in the present investigations are comparable to those achieved in clinical situations.^ The in vitro anticlastogenic effect of these retinoids and antioxidants may constitute an important element of their chemopreventive properties. The results corroborate the hypothesis that these compounds may be effective in clinical chemoprevention trials. The bleomycin-assay may also be used as a short-term test to evaluate the antimutagenic effects of various agents. ^

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We designed and synthesized a novel daunorubicin (DNR) analogue that effectively circumvents P-glycoprotein (P-gp)-mediated drug resistance. The fully protected carbohydrate intermediate 1,2-dibromoacosamine was prepared from acosamine and effectively coupled to daunomycinone in high yield. Deprotection under alkaline conditions yielded 2$\sp\prime$-bromo-4$\sp\prime$-epidaunorubicin (WP401). The in vitro cytotoxicity and cellular and molecular pharmacology of WP401 were compared with those of DNR in a panel of wild-type cell lines (KB-3-1, P388S, and HL60S) and their multidrug-resistant (MDR) counterparts (KB-V1, P388/DOX, and HL60/DOX). Fluorescent spectrophotometry, flow cytometry, and confocal laser scanning microscopy were used to measure intracellular accumulation, retention, and subcellular distribution of these agents. All MDR cell lines exhibited reduced DNR uptake that was restored, upon incubation with either verapamil (VER) or cyclosporin A (CSA), to the level found in sensitive cell lines. In contrast, the uptake of WP401 was essentially the same in the absence or presence of VER or CSA in all tested cell lines. The in vitro cytotoxicity of WP401 was similar to that of DNR in the sensitive cell lines but significantly higher in resistant cell lines (resistance index (RI) of 2-6 for WP401 vs 75-85 for DNR). To ascertain whether drug-mediated cytotoxicity and retention were accompanied by DNA strand breaks, DNA single- and double-strand breaks were assessed by alkaline elution. High levels of such breaks were obtained using 0.1-2 $\mu$g/mL of WP401 in both sensitive and resistant cells. In contrast, DNR caused strand breaks only in sensitive cells and not much in resistant cells. We also compared drug-induced DNA fragmentation similar to that induced by DNR. However, in P-gp-positive cells, WP401 induced 2- to 5-fold more DNA fragmentation than DNR. This increased DNA strand breakage by WP401 was correlated with its increased uptake and cytotoxicity in these cell lines. Overall these results indicate that WP401 is more cytotoxic than DNR in MDR cells and that this phenomenon might be related to the reduced basicity of the amino group and increased lipophilicity of WP401. ^

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This volume represents the proceedings of the Sixteenth Annual Biochemical Engineering Symposium held at Kansas State University on April 26, 1986. Some of the papers describe the progress of ongoing projects, and others contain the results of completed projects. Only brief summaries are given of many of the papers that will be published in full elsewhere. ContentsEnd-Product Inhibition of the Acetone-Butanol Fermentation—Bob Kuhn, Colorado State University Effect of Multiple Substrates in Ethanal Fermentations from Cheese Whey—C.J. Wang, University of Missouri Extraction and Fermentation of Ensiled Sweet Sorghum—Karl Noah, Colorado State University Removal of Nucleic Acids from Bakers' Yeast—Richard M. Cordes, Iowa State University Modeling the Effects of Plasmid Replication and Product Repression on the Growth Rate of Recombinant Bacteria—William E. Bentley, University of Colorado Indirect Estimates of Cell Concentrations in Mass Cultivation of Bacterial Cells—Andrew Fisher, University of Missouri A Mathematical Model for Liquid Recirculation in Airlift Columns—C.H.Lee, Kansas State University Characterization of Imperfect Mixing of Batch Reactors by Two Compartment Model—Peter Sohn, University of Missouri First Order Breakage Model for the Degradation of Pullalan in the Batch Fermentor—Stephen A. Milligan, Kansas State University Synthesis and Nuclear Magnetic Resonance of 13C-Labeled Amylopectin and Maltooligosaccharides—Bernard Y. Tao, Iowa State University Preparation of Fungal Starter Culture in Gas Fluidized Bed Reactor—Pal Mihaltz, Colorado State University Yeast Flocculation and Sedimentation—David Szlag, University of Colorado Protein Enrichment of Extrusion Cooked Corn by Solid Substrate Fermentation—Lucas Alvarez-Martinez, Colorado State University Optimum Design of a Hollow Fiber Mammalian Cell Reactor—Thomas Chresand, Colorado State University Gas Chromatography and Nuclear Magnetic Resonance of Trifluoroacetylated Carbohydrates—Steven T. Summerfelt, Iowa State University Kinetic and Bioenergetic Considerations for Modeling Photosynthetic Microbial P~ocesses in Producing Biomass and Treating Wastewater—H. Y. Lee, Kansas State University Mathematical Modeling and Simulation of Bicarbonate-Limited Photsynthetic Growth in Continuous Culture—Craig Curless, Kansas State University Data Acquisition and Control of a Rotary Drum Solid State Fermentor—Mnasria A. Habib, Colorado State University Biodegradation of 2,4-Dichlorophenoxyacetic Acid (2,4-D)—Greg Sinton, Kansas State University

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El presente trabajo tiene como propósito abordar los Diarios de mi vida de Rufino Blanco Fombona a través de un análisis de las diferentes imágenes que de sí da el diarista a lo largo del diario a partir de dos vertientes: su autofiguración artística y mundana y su autofiguración política. Al mismo tiempo, busca realizar un acercamiento a aquellos momentos de quiebre en los que la intimidad se manifiesta, corroyendo y desestabilizando esas imágenes y la propia escritura.

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La recuperación económica de Argentina desde 2003 impactó favorablemente en las diversas regiones del país, en especial, aquéllas muy vinculadas con el sector industrial y agropecuario de la economía. Entre ellas se destacan: el Aglomerado Gran Rosario (AGR) y el Aglomerado Gran Córdoba (AGCBA), dos de las aglomeraciones urbanas de mayor población después del Gran Buenos Aires. Este trabajo evalúa la dinámica productiva de ambas regiones, analizando las características del crecimiento experimentado en la última década e identificando aquellos aspectos de la estructura productiva que condicionan y/o favorecen la sustentabilidad del mismo. Se asume que un mayor grado de diversificación económica hacia sectores más intensivos en conocimiento es un factor importante para el logro de un crecimiento sostenido. Se observa en el AGCBA una mayor cantidad de variables socioeconómicas que muestran entre 2003 y 2013 una tasa de crecimiento promedio superior al del AGR. Dicho desempeño podría estar asociado a algunas características estructurales como son: la menor diversificación sectorial de la industria, un mayor peso relativo de sectores con uso intensivo de recursos naturales en comparación con sectores intensivos en conocimiento, una participación más alta de actividades “más informales" en el empleo total (construcción, servicio doméstico).

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El fenómeno de agriculturización que ha tenido lugar en nuestro país durante los últimos años no ha impactado solamente en la región de la República Argentina tradicionalmente agrícola. También lo ha hecho, aunque de una manera diferente, en la Provincia de San Luis. En esta provincia, dicho fenómeno convive con otras particularidades, como es la radicación industrial promocionada, que marcó profundamente el aparato productivo provincial o, más recientemente, una política pública de amplio espectro como el Plan de Inclusión Social, que modificó drásticamente los indicadores del mercado laboral sanluiseño. Este trabajo tiene por objeto estudiar la situación laboral de dos localidades de la Provincia de San Luis emplazadas en zonas de importante producción agrícola, considerando la influencia de las políticas públicas locales y del sector industrial que aún mantiene una importante cuota del Producto Bruto Geográfico. Para esto se realiza un análisis comparativo entre ellas y con la situación provincial, caracterizada por el Aglomerado San Luis y El Chorrillo, que releva la Encuesta Permanente de Hogares del indec. La información utilizada proviene de datos secundarios procedentes de organismos nacionales y de relevamientos propios realizados en las localidades estudiadas

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Este trabajo se propone hacer un aporte al estudio de la situación laboral de los jóvenes en un aglomerado argentino en particular, el Gran La Plata, conformado por los partidos de La Plata 'capital de la Provincia de Buenos aires', Berisso y Ensenada. Se trata de un aglomerado urbano que, en líneas generales, ha atravesado por procesos similares a los constatados a nivel nacional en el mercado de trabajo, así como en relación con la evolución de los indicadores de pobreza e indigencia. Distintos estudios han aportado a una caracterización completa del mercado de trabajo local desde principios de los años noventa, pero no se han realizado investigaciones específicas sobre la problemática laboral juvenil en el aglomerado. El período seleccionado para realizar este estudio comprende los años 2003 a 2006, momento en el cual se produjo un crecimiento constante de la economía nacional en el que se visualizaron mejoras generales en los niveles de empleo y bajas en los niveles de pobreza e indigencia. Al tiempo que cabe tener en cuenta que estas mejoras 'si bien importantes' no representan una recuperación de los niveles previos a la década del noventa, es preciso destacar, como remarcan algunos autores, que los incrementos en el empleo y las disminuciones en las tasas de desocupación y subocupación no implican que se hayan revertido problemas estructurales como la segmentación y precarización laboral, con sus efectos sobre las condiciones de vida de los trabajadores. esto hace particularmente interesante el estudio de la situación de los jóvenes, dadas las especificidades como grupo que adquieren en el mercado de trabajo. Se utilizan los datos pertenecientes a la encuesta Permanente de Hogares del Indec disponibles de la versión continua (2003-2006), considerando el segundo semestre de cada año