Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice.

High-risk human papillomaviruses (HPVs), including type 16, have been identified as factors in cervical carcinogenesis. However, the presence and expression of the virus per se appear to be insufficient for carcinogenesis. Rather, cofactors most likely are necessary in addition to viral gene expression to initiate neoplasia. One candidate cofactor is prolonged exposure to sex hormones. To examine the possible effects of estrogen on HPV-associated neoplasia, we treated transgenic mice expressing the oncogenes of HPV16 under control of the human keratin-14 promoter (K14-HPV16 transgenic mice) and nontransgenic control mice with slow release pellets of 17beta-estradiol. Squamous carcinomas developed in a multistage pathway exclusively in the vagina and cervix of K14-HPV16 transgenic mice. Estrogen-induced carcinogenesis was accompanied by an incremental increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-HPV16 mice. Expression of the HPV transgenes in untreated transgenic mice was detectable only during estrus; estrogen treatment resulted in transgene expression that was persistent but not further upregulated, remaining at low levels at all stages of carcinogenesis. The data demonstrate a novel mechanism of synergistic cooperation between chronic estrogen exposure and the oncogenes of HPV16 that coordinates squamous carcinogenesis in the female reproductive tract of K14-HPV16 transgenic mice.

Enteropathogenic Escherichia coli contains a putative type III secretion system necessary for the export of proteins involved in attaching and effacing lesion formation.

Enteropathogenic Escherichia coli (EPEC) causes a characteristic histopathology in intestinal epithelial cells called the attaching and effacing lesion. Although the histopathological lesion is well described the bacterial factors responsible for it are poorly characterized. We have identified four EPEC chromosomal genes whose predicted protein sequences are similar to components of a recently described secretory pathway (type III) responsible for exporting proteins lacking a typical signal sequence. We have designated the genes sepA, sepB, sepC, and sepD (sep, for secretion of E. coli proteins). The predicted Sep polypeptides are similar to the Lcr (low calcium response) and Ysc (yersinia secretion) proteins of Yersinia species and the Mxi (membrane expression of invasion plasmid antigens) and Spa (surface presentation of antigens) regions of Shigella flexneri. Culture supernatants of EPEC strain E2348/69 contain several polypeptides ranging in size from 110 kDa to 19 kDa. Proteins of comparable size were recognized by human convalescent serum from a volunteer experimentally infected with strain E2348/69. A sepB mutant of EPEC secreted only the 110-kDa polypeptide and was defective in the formation of attaching and effacing lesions and protein-tyrosine phosphorylation in tissue culture cells. These phenotypes were restored upon complementation with a plasmid carrying an intact sepB gene. These data suggest that the EPEC Sep proteins are components of a type III secretory apparatus necessary for the export of virulence determinants.

Refinery Nonconventional Feedstocks: Influence of the Coprocessing of Vacuum Gas Oil and Low Density Polyethylene in Fluid Catalytic Cracking Unit on Full Range Gasoline Composition

Gasoline coming from refinery fluid catalytic cracking (FCC) unit is a major contributor to the total commercial grade gasoline pool. The contents of the FCC gasoline are primarily paraffins, naphthenes, olefins, aromatics, and undesirables such as sulfur and sulfur containing compounds in low quantities. The proportions of these components in the FCC gasoline invariable determine its quality as well as the performance of the associated downstream units. The increasing demand for cleaner and lighter fuels significantly influences the need not only for novel processing technologies but also for alternative refinery and petrochemical feedstocks. Current and future clean gasoline requirements include increased isoparaffins contents, reduced olefin contents, reduced aromatics, reduced benzene, and reduced sulfur contents. The present study is aimed at investigating the effect of processing an unconventional refinery feedstock, composed of blend of vacuum gas oil (VGO) and low density polyethylene (LDPE) on FCC full range gasoline yields and compositional spectrum including its paraffins, isoparaffins, olefins, napthenes, and aromatics contents distribution within a range of operating variables of temperature (500–700 °C) and catalyst-feed oil ratio (CFR 5–10) using spent equilibrium FCC Y-zeolite based catalyst in a FCC pilot plant operated at the University of Alicante’s Research Institute of Chemical Process Engineering (RICPE). The coprocessing of the oil-polymer blend led to the production of gasoline with very similar yields and compositions as those obtained from the base oil, albeit, in some cases, the contribution of the feed polymer content as well as the processing variables on the gasoline compositional spectrum were appreciated. Carbon content analysis showed a higher fraction of the C9–C12 compounds at all catalyst rates employed and for both feedstocks. The gasoline’s paraffinicity, olefinicity, and degrees of branching of the paraffins and olefins were also affected in various degrees by the scale of operating severity. In the majority of the cases, the gasoline aromatics tended toward the decrease as the reactor temperature was increased. While the paraffins and iso-paraffins gasoline contents were relatively stable at around 5 % wt, the olefin contents on the other hand generally increased with increase in the FCC reactor temperature.

Abordagem terapêutica da papilomatose laríngea : a propósito de um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

SHRIMP U-Pb dating of high-grade migmatites and related magmatites from Northwestern Oates Land, East Antarctica

High- to very-high-grade migmatitic basement rocks of the Wilson Hills area in northwestern Oates Land (Antarctica) form part of a low-pressure high-temperature belt located at the western inboard side of the Ross-orogenic Wilson Terrane. Zircon, and in part monazite, from four very-high grade migmatites (migmatitic gneisses to diatexites) and zircon from two undeformed granitic dykes from a central granulite-facies zone of the basement complex were dated by the SHRIMP U-Pb method in order to constrain the timing of metamorphic and related igneous processes and to identify possible age inheritance. Monazite from two migmatites yielded within error identical ages of 499 +/- 10 Ma and 493 +/- 9 Ma. Coexisting zircon gave ages of 500 +/- 4 Ma and 484 +/- 5 Ma for a metatexite (two age populations) and 475 +/- 4 Ma for a diatexite. Zircon populations from a migmatitic gneiss and a posttectonic granitic dyke yielded well-defined ages of 488 +/- 6 Ma and 482 +/- 4 Ma, respectively. There is only minor evidence of age inheritance in zircons of these four samples. Zircon from two other samples (metatexite, posttectonic granitic dyke) gave scattered 206Pb-238U ages. While there is a component similar in age and in low Th/U ratio to those of the other samples, inherited components with ages up to c. 3 Ga predominate. In the metatexite, a major detrital contribution from 545 - 680 Ma old source rocks can be identified. The new age data support the model that granulite- to high-amphibolite-facies metamorphism and related igneous processes in basement rocks of northwestern Oates Land were confined to a relatively short period of time of Late Cambrian to early Ordovican age. An age of approximately 500 Ma is estimated for the Ross-orogenic granulite-facies metamorphism from consistent ages of monazite from two migmatites and of the older zircon age population in one metatexite. The variably younger zircon ages are interpreted to reflect mineral formation in the course of the post-granulite-facies metamorphic evolution, which led to a widespread high-amphibolite-facies retrogression and in part late-stage formation of ms+bi assemblages in the basement rocks and which lasted until about 465 Ma. The presence of inherited zircon components of latest Neoproterozoic to Cambrian age indicates that the high- to very-grade migmatitic basement in northwestern Oates Land originated from clastic series of Cambrian age and, therefore, may well represent the deeper-crustal equivalent of lower-grade metasedimentary series of the Wilson Terrane.

Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX (TM) adjuvant in women with cervical intraepithelial neoplasia

Purpose: Persistent infection of cervical epithelium with high risk human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV 16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX(TM) adjuvant (HPV16 Immunotherapeutic) for patients with CIN. Experimental design: Patients with CIN (n = 3 1) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy. Results: Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients. Conclusions : The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX(TM) adjuvant is safe and induces vaccine antigen specific cell mediated immunity. (C) 2004 Elsevier Ltd. All rights reserved.

Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia

Purpose: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. Experimental Design: RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. Results: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARa, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and Pan IN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early Pan IN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. Conclusions: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.

Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast

Aims: Cytokeratin (CK) 14, a myoepithelial marker, is also expressed in a proportion of breast carcinomas. There is evidence that these tumours show a differing metastatic pattern and clinical outcome from other invasive ductal carcinomas (IDCs) and may need different management. Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC. Methods and results: A detailed histological review of 453 grade 3 IDCs revealed 88 (19.4%) that expressed CK14. Assessment was made independently by two pathologists using a standardized 'tick-box' proforma covering grade, architectural and cytological features. The results were analysed using logistic regression to identify features that predicted for basal phenotype. Concordance between the two pathologists was fair to good for most parameters (kappa 0.4-0.6). On multiple logistic regression, the basal phenotype was highly significantly associated with the presence of a central scar (P = 0.005), tumour necrosis (P < 0.0001), presence of spindle cells (P = 0.006) or squamous metaplasia (P < 0.0001), high total mitotic count (> 40 per 10 high-power field) (P = 0.0002) and high nuclear-cytoplasmic ratio (P = 0.0002). Conclusions: Specific morphological features are strongly associated with basal-like breast carcinoma. These could be used in routine diagnostic practice to identify this important subset of tumours.

Low frequency dielectric spectroscopy of bitumen binders as an indicator of adhesion potential to quartz aggregates using Portland cement

The purpose of this investigation was to interpret the bitumen-aggregate adhesion based on the dielectric spectroscopic response of individual material components utilizing their dielectric constants, refractive indices and average tangent of the dielectric loss angle (average loss tangent). Dielectric spectroscopy of bitumen binders at room temperature was performed in the frequency range of 0.01–1000 Hz. Dielectric spectroscopy is an experimental method for characterizing the dielectric permittivity of a material as a function of frequency. Adhesion data has been determined using the Rolling bottle method. The results show that the magnitude of the average tangent of the dielectric loss angle (average loss tangent) depends on bitumen type. The average loss tangent in the frequency range 0.01–1 Hz is introduced as a potential indicator for predicting polarizability and, thereby, adhesion potential of bitumen binders to quartz aggregates when using Portland cement. In order to obtain acceptable adhesion of 70/100 penetration grade bitumen binders and quartz aggregates when using Portland cement, it is suggested that the binder have an average tan δ > 0.035 in the frequency range 0.01–1 Hz.

A fourth-grade teacher's classroom perspective

Countless books have been written about what is good and what is bad about our educational system. No matter what the book or what the theory, all agree the classroom teacher is critical to the education process. Many influences affect classroom teaching, some of which are beyond her control, but a caring classroom teacher has a central role in the instruction of children The purpose of this case study was to inquire into the beliefs and behaviors of one elementary school teacher in a low socio-economic school and study her classroom perspective. This teacher of five years was a reading specialist and was teaching a full fourth grade curriculum for the first time. Because she suffered from math phobia, she was apprehensive about teaching mathematics. ^ This qualitative study required intense, time-consuming interviews, long and frequent observations, critical journaling, field notes and artifacts provided by the teacher. The resulting descriptive data was coded into categories and reassembled into themes that captured the essence of the teacher's beliefs. ^ The overarching themes found were: first, the teacher's caring attitude towards her students, cultivated by her affectionate family, her mother who is an elementary school teacher, and rich and rewarding elementary school experiences, second, her implementation of the curriculum, influenced by her passion for reading, her math phobia, and standardized tests and third, her attitudes toward her workplace, school administrators and collegiality among teachers. During the school year this teacher “owned” her classroom and was a full participant in its life! Her dedication to teaching was fostered by the satisfaction of knowing she has a profound impact and makes a significant difference in her students' lives. ^ This study suggested areas for further research on the following topics: consideration of teachers with math phobia, the effect of standardized tests on areas of the curriculum and the value of computers in the elementary school classroom. ^

A comparison of content-based and context-based teaching on ninth-grade mathematics achievement

The purpose of this study was to determine if an experimental context-based delivery format for mathematics would be more effective than a traditional model for increasing the performance in mathematics of at-risk students in a public high school of choice, as evidenced by significant gains in achievement on the standards-based Mathematics subtest of the FCAT and final academic grades in Algebra I. The guiding rationale for this approach is captured in the Secretary's Commission on Achieving Necessary Skills (SCANS) report of 1992 that resulted in school-to-work initiatives (United States Department of Labor). Also, the charge for educational reform has been codified at the state level as Educational Accountability Act of 1971 (Florida Statutes, 1995) and at the national level as embodied in the No Child Left Behind Act of 2001. A particular focus of educational reform is low performing, at-risk students. ^ This dissertation explored the effects of a context-based curricular reform designed to enhance the content of Algebra I content utilizing a research design consisting of two delivery models: a traditional content-based course; and, a thematically structured, content-based course. In this case, the thematic element was business education as there are many advocates in career education who assert that this format engages students who are often otherwise disinterested in mathematics in a relevant, SCANS skills setting. The subjects in each supplementary course were ninth grade students who were both low performers in eighth grade mathematics and who had not passed the eighth grade administration of the standards-based FCAT Mathematics subtest. The sample size was limited to two groups of 25 students and two teachers. The site for this study was a public charter school. Student-generated performance data were analyzed using descriptive statistics. ^ Results indicated that contrary to the beliefs held by many, contextual presentation of content did not cause significant gains in either academic performance or test performance for those in the experimental treatment group. Further, results indicated that there was no meaningful difference in performance between the two groups. ^

The relationship between prekindergarten social and emotional development and academic success among Hispanic children from low-income families

Social and emotional development has been considered an important factor in child development which has been placed at the end of the learning spectrum due to high stakes testing. Social and emotional development consists of the relationships an individual has with others, the level of self-control, and the motivation and perseverance a person has during an activity (Bandura, 1989). This study examined the relationship between Hispanic children’s prekindergarten social and emotional development and their academic success. Hispanic children from a large southeastern city whose parents were receiving subsidized child-care were followed from their prekindergarten year through third grade (N=1,978). Several hierarchical regressions were run to determine the relationship between children’s social and emotional development, during their prekindergarten year using the DECA (Devereaux Early Childhood Assessment), and the their academic success, as measured by kindergarten through third grade end of the year reading and mathematics academic grades, second grade SAT (Stanford Achievement Test) scores, and third grade FCAT (Florida Comprehensive Assessment Test) and NRT (Norm Referenced Test) scores. Hierarchical regressions were conducted for each grade and subject in order to control for demographics and prior achievement. The results of this study revealed that for Hispanic children from low-income families, the best predictor for academic success was the children’s prior academic achievement. Social and emotional development showed no significant predictive value for the third grade criterion variables as well as end of the year academic grades in second grade and kindergarten reading. Evidence did suggest that for first grade end of the year academic grades and kindergarten math, social and emotional development had a small predictive value. Further research must be conducted as to why social and emotional development, after controlling for demographics and previous academic achievement, bears such a small predictive value when it is clear that many professionals feel it is the most important factor for school readiness.

A study of the relationship between educational placement and the achievement of urban low socioeconomic Hispanic middle school students with and without specific learning disabilities

Public schools traditionally have been held accountable for educating the majority of the nation’s school children, and through the years, these schools have been evaluated in a variety of ways. Currently, evaluation measures for accountability purposes consist solely of standardized test scores. In the past, only test scores of general education students were analyzed. Laws governing the education of students with disabilities, however, have extended accountability measures not only to include those students, but to report their scores in a disaggregated form (No Child Left Behind Act, 2001). The recent emphasis on accountability and compliance has resulted in the need for schools to carefully examine how programs, services, and policies impact student achievement (Bowers & Figgers, 2003). ^ Standard-based school reform and accountability systems have raised expectations about student learning outcomes for all students, including those with disabilities and minority students. Yet, overall, racial/ethnic minority students are performing well below their White non-Hispanic peers in most academic areas. Additionally, with respect to special education, there exists an enduring problem of disproportionate representation of racial/ethnic minority students (National Research Council, 2000). ^ This study examined classroom placement (inclusive versus non-inclusive) relative to academic performance of urban, low socioeconomic Hispanic students with and without disabilities in secondary content area classrooms. A mixed method research design was used to investigate this important issue using data from a local school district and results from field observations. The study compared performance levels of four middle school Hispanic student subgroups (students with disabilities in inclusive settings, students without disabilities in inclusive settings, students with disabilities in resource settings, and student without disabilities in general education settings) each in their respective placements for two consecutive years, exploring existing practices within authentic settings. ^ Significant differences were found in the relationship of educational placement and achievement between grade level and disability in the areas of math and reading. Additionally, clear and important differences were observed in student-teacher interactions. Recommendations for further researchers and stakeholders include soliciting responses from teams at the schools composed of general education and special education teachers, administrative personnel, and students as well as broadening the study across grade levels and exceptionalities. ^

A comparative study of high -achieving and low -achieving African -American students in an urban setting

The purpose of this study was to delineate which demographic and school variables were important for predicting the achievement of 10th grade African-American students. The sample population was divided into two groups: high-achievers, students with GPAs of 3.5 or higher, and low-achievers, students with GPAs of 1.5 or lower. Variables examined in the study included: gender; birth place; student's native language; exceptionality (ESE); history of English proficiency (LEP); SES (lunch status) in elementary and high school; the percentage of the Black student population in high school; and suspensions, absences, tardies, and the Stanford Achievement Test (SAT) scores in reading comprehension, mathematics computation, and mathematics applications in elementary and middle school. Two separate logistic regression analyses were conducted to determine which variables were influential in predicting achievement.^ Analysis 1 (N = 366), which included all the variables, except the SAT percentile scores, correctly classified 87% of the students as high-achievers or low-achievers. The results from Analysis 1 revealed that students who--were female; spoke a language other than English as their first language; did not apply for free or reduced lunch in elementary school; were in the gifted program; had no absences or tardies in elementary school; had no suspensions or tardies in middle school; and attended a high school with a lower percentage of Black students--were more likely to be high-achieving than low-achieving.^ Analysis 2 (N = 274) included all the variables and resulted in 94% of the students being correctly classified. It was found that students who--were female; were currently or previously classified as Limited English Proficient (LEP); did not apply for free or reduced lunch in elementary school; had no suspensions or tardies in middle school; and had higher percentile scores in reading comprehension and mathematics computation on the SAT in middle school--were more likely to high-achieving than low-achieving.^ The quantitative analyses were coupled with interviews from a purposeful sample of the population (N = 12) to gain additional insight about why some African-American students are succeeding in our schools and others are not. This study provides a viable means for assessing African-American students' achievement patterns in our schools. ^

Access to better education: The school choice experience of families served by low-performing elementary public schools in Miami-Dade County

Public school choice education policy attempts to create an education marketplace. Although school choice research has focused on the parent role in the school choice process, little is known about parents served by low-performing schools. Following market theory, students attending low-performing schools should be the primary students attempting to use school choice policy to access high performing schools rather than moving to a better school. However, students remain in these low-performing schools. This study took place in Miami-Dade County, which offers a wide variety of school choice options through charter schools, magnet schools, and open-choice schools. ^ This dissertation utilized a mixed-methods design to examine the decision-making process and school choice options utilized by the parents of students served by low-performing elementary schools in Miami-Dade County. Twenty-two semi-structured interviews were conducted with the parents of students served by low-performing schools. Binary logistic regression models were fitted to the data to compare the demographic characteristics, academic achievement and distance from alternative schooling options between transfers and non-transfers. Multinomial logistic regression models were fitted to the data to evaluate how demographic characteristics, distance to transfer school, and transfer school grade influenced the type of school a transfer student chose. A geographic analysis was conducted to determine how many miles students lived from alternative schooling options and the miles transfer students lived away from their transfer school. ^ The findings of the interview data illustrated that parents’ perceived needs are not being adequately addressed by state policy and county programs. The statistical analysis found that students from higher socioeconomic social groups were not more likely to transfer than students from lower socioeconomic social groups. Additionally, students who did transfer were not likely to end up at a high achieving school. The findings of the binary logistic regression demonstrated that transfer students were significantly more likely to live near alternative school options.^