Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16-associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus-like particles was assessed in patients with CIN 2 (n = 169) and CIN 3 (n = 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA-positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P = 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16-associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16-associated CIN 3 in patient population studied.

SIFA: A tool for evaluation of high-grade security devices

We describe a tool for analysing information flow in security hardware. It identifies both sub-circuits critical to the preservation of security as well as the potential for information flow due to hardware failure. The tool allows for the composition of both logical and physical views of circuit designs. An example based on a cryptographic device is provided.

Heparanase and COX-2 expression as predictors of lymph node metastasis in large, high-grade breast tumors

Background/Aim: Heparanase (HPA) contributes to breast cancer metastasis by facilitating the breakdown of the basement membrane and extracellular matrix. High expression of HPA is thought to be associated with increased nodal involvement and poor survival in patients with breast cancer. Overexpression of cyclooxygenase-2 (COX-2) in breast cancer is associated with indicators of poor prognosis such as lymph node metastasis, poor differentiation, and large tumor size. The underlying mechanism by which HPA and COX-2 overexpression increases the metastatic potential of breast cancer is not fully-understood. To enhance our understanding over these mechanisms, we aimed to investigate the relationship between the size of the tumor and HPA expression, tumor grade as well as lymph node status in patients with breast cancer. Materials and Methods: Immunohistochemical analysis of HPA and COX-2 expression was performed on 246 breast tumor samples. The expression of HPA was correlated with COX-2 expression, tumor grade, lymph node status, oestrogen receptor status. Results: The overexpression of HPA and COX-2 was associated with increased likelihood of lymph node positivity in large, high-grade tumors. High-grade tumors with size greater than 20 mm, that overexpressed HPA, were 4-times more likely to be associated with lymph node involvement (OR 4.71, CI 1.21-18.25). Whereas, tumors greater than 20 mm in size were 5-times more likely to metastasize to the regional lymph nodes, if associated with overexpression of COX-2 (OR 5.5, CI 1.2-24.8). Conclusion: Expression of HPA appears to be a key mechanism by which large, highgrade breast tumors metastasize to regional lymph nodes, while COX-2 overexpression may be an independent predictor of lymph node positivity.

ROLE OF STAT1 AND CXCL10 IN THE TUMOUR IMMUNE MICROENVIRONMENT OF HIGH-GRADE SEROUS OVARIAN CANCER

High-grade serous ovarian cancer (HGSC) is the most prevalent epithelial ovarian cancer characterized by late detection, metastasis and resistance to chemotherapy. Previous studies on the tumour immune microenvironment in HGSC identified STAT1 and CXCL10 as the most differentially expressed genes between treatment naïve chemotherapy resistant and sensitive tumours. Interferon-induced STAT1 is a transcription factor, which induces many genes including tumour suppressor genes and those involved in recruitment of immune cells to the tumour immune microenvironment (TME), including CXCL10. CXCL10 is a chemokine that recruits tumour infiltrating lymphocytes (TILs) and exhibits angiostatic function. The current study was performed to determine the effects of differential STAT1 and CXCL10 expression on HGSC disease progression and TME. STAT1 expression and intratumoural CD8+ T cells were evaluated as prognostic and predictive biomarkers via immunohistochemistry on 734 HGSC tumours accrued from the Terry Fox Research Institute-Canadian Ovarian Experimental Unified Resource. The combined effect of STAT1 expression and CD8+ TIL density was confirmed as prognostic and predictive companion biomarkers in the second independent biomarker validation study. Significant positive correlation between STAT1 expression and intratumoral CD8+ TIL density was observed. The effects of enforced CXCL10 expression on HGSC tumour growth, vasculature and immune tumour microenvironment were studied in the ID8 mouse ovarian cancer cell engraftment in immunocompetent C57BL/6 mice. Significant decrease in tumour progression in mice injected with ID8 CXCL10 overexpressing cells compared to mice injected with ID8 vector control cells was observed. Multiplexed cytokine analysis of ascites showed differential expression of IL-6, VEGF and CXCL9 between the two groups. Endothelial cell marker staining showed differences in tumour vasculature between the two groups. Immune transcriptomic profiling identified distinct expression profiles in genes associated with cytokines, chemokines, interferons, T cell function and apoptosis between the two groups. These findings provide evidence that STAT1 is an independent biomarker and in combination with CD8+ TIL density could be applied as novel immune-based biomarkers in HGSC. These results provide the basis for future studies aimed at understanding mechanisms underlying differential tumour STAT1 and CXCL10 expression and its role in pre-existing tumour immunologic diversity, thus potentially contributing to biomarker guided immune modulatory therapies.

Transformation to "high grade" neuroendocrine carcinoma as an acquired drug resistance mechanism in EGFR-mutant lung adenocarcinoma.

Several different acquired resistance mechanisms of EGFR mutant lung adenocarcinoma to EGFR-tyrosine kinase inhibitor (TKI) therapy have been described, most recently transformation to small cell lung carcinoma (SCLC). We describe the case of a 46-year-old female with relapsed EGFR exon 19 deletion lung adenocarcinoma treated with erlotinib, and on resistance, cisplatin-pemetrexed. Liver rebiopsy identified an afatinib-resistant combined SCLC and non-small cell carcinoma with neuroendocrine morphology, retaining the EGFR exon 19 deletion. This case highlights acquired EGFR-TKI resistance through transformation to the high-grade neuroendocrine carcinoma spectrum and that that such transformation may not be evident at time of progression on TKI therapy.

Numerical simulations of CO2 migration during charnockite genesis

Charnockite is considered to be generated either through the dehydration of granitic magma by CO2 purging or by solid-state dehydration through CO2 metasomatism during granulite facies metamorphism. To understand the extent of dehydration, CO2 migration is quantitatively modeled in silicate melt and metasomatic fluid as a function of temperature, H2O wt%, pressure, basal CO2 flux and dynamic viscosity. Numerical simulations show that CO2 advection through porous and permeable high-grade metamorphic rocks can generate dehydrated patches close to the CO2 flow path, as illustrated by the occurrences of ``incipient charnockites.'' CO2 reaction-front velocity constrained by field observations is 0.69 km/m.y., a reasonable value, which matches well with other studies. On the other hand, temperature, rate of cooling, and basal CO2 flux are the critical parameters affecting CO2 diffusion through a silicate melt. CO2 diffusion through silicate melt can only occur at temperature greater than 840 degrees C and during slow cooling (<= 3.7 x 10(-5) degrees C/yr), features that are typical of magma emplacement in the lower crust. Stalling of CO2 fluxing at similar to 840 degrees C explains why some deep-level plutons contain both hydrous and anhydrous (charnockitic) mineral assemblages. CO2 diffusion through silicate melt is virtually insensitive to pressure. Addition of CO2 basal flux facilitates episodic dehydrated melt migration by generating fracture pathways.

Metalogenia em terrenos de alto grau metamórfico: as mineralizações tungstaníferas da área de Monumento/Cacaria RJ

Em trabalho de prospecção geoquímica regional por concentrado de bateia (PEREIRA e SANTOS, 1983) foi evidenciado na região de Cacaria, município de Piraí, ocorrências de scheelita. Com o objetivo de investigar a possível fonte litológica desta ocorrência, foram realizadas amostragens de sedimentos de corrente e concentrado de bateia além de investigações de campo para sua fonte. Elaborouse ainda um mapa geológico em escala de detalhe 1:25.000. As unidades estratigráficas base utilizadas no mapa foram definidas em trabalhos da empresa RIOFINEX (1977) durante pesquisas para mineralizações de Pb-Zn na região de Rio Claro. Ensaios laboratoriais envolvendo descrição de lâminas petrográficas, difratometria de raios X, fluorescência de raios X, espectrometria Raman, microscopia eletrônica de varredura e o auxílio do mineralight de ondas curtas. As mineralizações scheelitíferas encontradas foram classificadas segundo um modelo do tipo sedimentar exalativo, localmente com possíveis contribuições de atividades metassomáticas tardias, concentrando a mineralização, assim como proposto para algumas ocorrências já descritas no nordeste brasileiro.

化德群和土门群沉积岩碎屑锆石研究：对华北克拉通基底及元古宙盆地演化的指示意义

The Huade Group, consisting of low-grade and un-metamorphosed sedimentary rocks with no volcanic interlayer, is located at the northern margin of the North China craton and adjoining the south part of the Central Asian Orogenic Belt. It is east to the Paleo- to Meso-Proterozoic Bayan Obo and Zhaertai-Langshan rifts and northwest to the Paleo- to Neo-proterozoic Yanshan aulacogen, in which the typical Changcheng, Jixian and Qingbaikou systems are developed. The Huade Group are mainly composed of pebbly sandstones, sandstones, greywackes，shales，calc-silicate rocks and limestones, partly undergoing low-grade metamorphism and being changed to meta-sandstones, schists, phyllites, slates and crystalline limestones or marbles. The stratigraphic sequences show several cycles of deposition. Each of them developed coarse clastic rocks – interbedded fine clastic rocks and pelites from bottom upward or from coarse clastic rocks to interbedded fine clastic rocks and pelites to carbonate rocks. The Tumen Group outcrop sporadically around or west to the Tanlu faults in western Shandong. They are mainly composed of pebbly sandstones, sandstones, shales and limestones. This thesis deals with the characteristics of petrology, geochemistry and sedimentary of the Huade Group and the Tumen Group, and discusses the LA-ICP-MS and SIMS U-Pb ages, Hf isotope and trace element composition of the detrital zircons from 5 meta-sandstone samples of the Huade Group and 3 sandstone samples of the Tumen Group. The age populations of the detrital zircons from the Huade Group are mainly ~2.5 Ga and ~1.85 Ga, and there are also minor peaks at ~2.0 Ga, ~1.92 Ga and ~1.73 Ga. Most of the detrital zircon grains of 2.47-2.57 Ga and a few of 1.63-2.03 Ga have Hf crust model ages of 2.7-3.0 Ga, and most of the detrital zircon grains of 1.63-2.03 Ga have Hf crust model ages of 2.35-2.7 Ga, with a peak at 2.54 Ga. The main age peaks of the detrital zircons from the Tumen Group are ~2.5 Ga、~1.85 Ga, 1.57 Ga, 1.5 Ga, 1.33 Ga and 1.2 Ga. Different samples from the Tumen Group have distinct Hf isotopic characteristics. Detrital zircon grains of ~2.52 Ga from one sandstone sample have 2.7-3.2 Ga Hf crust model ages, whereas zircon grains of 1.73-2.02 Ga and 2.31-2.68 Ga from another sample have Hf crust model ages of 2.95-3.55 Ga. Detrital zircon grains of Mesoproterozoic ages have Paleoproterozoic (1.7-2.25 Ga) crust model ages. Through detailed analyses of the detrital zircons from the Huade and Tumen Group and comparison with those from the sedimentary rocks of similar sedimentary ages, the thesis mainly reaches the following conclusions: 1. The youngest age peaks of the detrital zircons of 1.73 Ga constrains the sedimentary time of the Huade Group from late Paleoproterozoic to Mesoproterozoic. 2. The age peaks of detrital zircons of the Huade Group correspond to the significant Precambrian tectonic-thermal events of the North China craton. The basement of the North China craton is the main provenance of the Huade Group, of which the intermediate to high grade metamorphic sedimentary rocks are dominant and provide mainly 1.85-1.92 Ga sediments. 3. The Huade basin belongs to the North China craton and it is suggested that the northern boundary of the North China craton should be north to the Huade basin. 4. The stratigraphic characteristics indicate the Huade Group formed in a stable shallow-hypabyssal sedimentary basin. The rock association and sedimentary time of the Huade Group are similar to those of the Banyan Obo Group and the Zhaertai Group, and they commonly constitute late Paleoproterozoic to Mesoproterozoic continental margin basins along the northern margin of the North China craton. 5. The continental margin basins would have initiated coeval with the Yanshan and Xiong’er aulacogens. 6. The ages of the detrital zircons from the Tumen Group and the Penglai Group at Shandong peninsula and the Yushulazi Group at south Liaoning are similar, so their sedimentary time is suggested to be Neoproterozoic，coeval with the Qingbaikou system. The detrital zircon ages of 1.0-1.2 Ga from the Tumen Group, the Penglai Group and the Yushulazi Group indicate that there have being 1.0-1.2 Ga magmatic activities at the eastern margin of the North China craton. 7. The U-Pb age populations of the detrital zircons from the late Paleoproterozoic to Neoproterozoic sedimentary rocks suggest that the main Precambrian tectonic-thermal events of the North China craton happened at ~2.5 Ga and ~1.85 Ga. But the events at 2.7 Ga and 1.2 Ga are also of great significance. Hf isotope characteristics indicate that the significant crust growth periods of the North China craton are 2.7-3.0 Ga and ~2.5 Ga.

Caratterizzazione geo-petrografica, petrologica e geochimica di rocce anatettiche del nord Sardegna

The High Grade Metamorphic Complex (HGMC) of Variscan basement of north Sardinia is characterized by the widespread of migmatites. This study is focused on two localities of NE Sardinia (Porto Ottiolu and Punta Sirenella) where ortho- and para-derivates migmatites outcrop. A geological and structural survey was carried out, leading to the realization of a geological schematic map of Punta Sirenella area. Several samples of different rocks were collected for petrographic, micro-structural minero-chemical and geochemical analyses. In the Porto Ottiolu area three main deformation phases have been identified; D1, characterized by tight folds with sub-horizontal axes, rarely preserved in paragneisses; D2, that produce a pervasive foliation oriented N100° 45°SW marked by biotite and sillimanite blastesis and locally transposed by shear zone oriented N170°; D3, late deformation phase caused symmetric folds with sub-horizontal axes with no axial plane schistosity. Leucosomes form pods and layers along S2 schistosity but also leucosomes along shear zones have been observed. In the Punta Sirenella area, three main deformation phases have been identified; D1, is manifested by the transposition of centimeter-sized leucosomes and is rarely observed in paragneisses were produce open folds with sub-vertical axes; D2, NW-SE oriented on whose XY plane three mineralogical lineation (quartz+plagioclase, fibrolite+quarz and muscovite) lie; D3, a ductile-brittle deformation phase that produce a mylonitc S3 foliation that locally become the most evident schistosity in the field oriented N140° steeply dipping toward NE. In both areas, leucosomes of sedimentary-derived migmatites are generally trondhjemitic pointing out for a H2O fluxed melting reaction, but also granitic leucosomes have been found, produced by muscovite dehydration melting. Leucosomes of migmatitic orthogneiss instead, have granitic compositions. Migmatization started early, during the compressional and crustal thickening (sin-D1, pre-D2) and was still active during exhumation stage. For each studied outcrop of migmatite pseudosections for the average mesosome composition have been calculated; these pseudosections have been used to model the P-T conditions of anatexis on the basis of the melt volume (%) of melt, Si/Al and Na/K molar ratios, modal content of garnet and Si content in metamorphic white mica. Further pseudosections have been calculated for the average composition of leucosomes in order to define the P-T conditions of the end of the crystallization through intersection of solidus curve and isopleths of Si content in white mica and/or XMg ratio in biotite. Thermodynamic modeling on ortho- and sedimentary-derived migmatites of Punta Sirenella yield P-T conditions of 1.1-1.3 GPa - 670-740°C for migmatitic event and 0.75-0.90 GPa - 660-730°C for the end of crystallization. These conditions are fit well with previous studies on adjacent rocks. Modeling of Porto Ottiolu ortho- and sedimentary-derived migmatites yield P-T conditions of 0.85-1.05 GPa - 690-730°C for migmatitic event and 0.35-0.55 GPa - 630-690°C strongly affected by re-equilibration during exhumation, expecially for crystallization conditions. Geochemical analyses of samples belonging to Porto Ottiolu and Punta Sirenella orthogneisses show a strong link with those of other orthogneisses outcropping in NE Sardinia (for instance, Lode-Mamone and Golfo Aranci) that are considered the intrusive counterparts of middle-Ordovician metavolcanics rocks outcropping in the Nappe Zone. Thus, the studied ortogneiss bodies, even lacking radiometric data, can be considered as belonging to the same magmatic cycle.

Precambrian geotectonic units of the Rio de La Plata craton

The main Precambrian tectonic units of Uruguay include the Piedra Alta tectonostratigraphic terrane (PATT) and Nico Perez tectonostratigraphic terrane (NPTT), separated by the Sarandi del Yi high-strain zone. Both terranes are well exposed in the Rio de La Plata craton (RPC). Although these tectonic units are geographically small, they record a wide span of geologic time. Therefore improved geological knowledge of this area provides a fuller understanding of the evolution of the core of South America. The PATT is constituted by low-to medium-grade metamorphic belts (ca. 2.1 Ga); its petrotectonic associations such as metavolcanic units, conglomerates, banded iron formations, and turbiditic deposits suggest a back-arc or a trench-basin setting. Also in the PATT, a late to post-orogenic, arc-related layered mafic complex (2.3-1.9 Ga), followed by A-type granites (2.08 Ga), and finally a taphrogenic mafic dike swarm (1.78 Ga) occur. The less thoroughly studied NPTT consists of Palaeoproterozoic high-grade metamorphic sequences (ca. 2.2 Ga), mylonites and postorogenic and rapakivi granites (1.75 Ga). The Brasiliano-Pan African orogeny affected this terrane. Neoproterozoic cover occurs in both tectonostratigraphic terranes, but is more developed in the NPTT. Over the past 15 years, new isotopic studies have improved our recognition of different tectonic events and associated processes, such as reactivation of shear zones and fluids circulation. Transamazonian and Statherian tectonic events were recognized in the RPC. Based on magmatism, deformation, basin development and metamorphism, we propose a scheme for the Precambrian tectonic evolution of Uruguay, which is summarized in the first Palaeoproterozoic tectonic map of the Rio de La Plata craton.

Geotermobarometria de Granulitos Associados à Supracrustais na Porção Norte do Complexo Guaxupé - Região de Arceburgo - Santa Cruz do Prata, MG

This paper is a contribution for the understanding of the geological evolution of Guaxupé Complex. New data on petrography and mineral chemistry as well as estimates of metamorphic (P-T) conditions in the region of Arceburgo - Santa Cruz do Prata (MG) Brazil, at the southern portion of the Brasília Belt, more specifically at the Guaxupé Complex (Domain) are now presented. The lithotypes are high-grade metamorphic rocks subdivided into two groups: metasediments and granulites (orthoderivates). Chemical analysis of minerals was performed in three steps including core and rim of amphibole, pyroxene, feldspar, biotite, and garnet from samples of the following rock types: enderbites, mafic granulites, charnockites, and alkali feldspar charnockites. Results obtained with geothermobarometric calculations show metamorphic peak around 900°C of T and 10 kbar of P. Enderbites and tonalite granulites (mafic) show the highest values of temperature and pressure, while alkali feldspar charnockites show the lowest probably due to their late generation in relation to mafic rock types (enderbites and mafic tonalite granulite). Chemical mineral analysis in metamorphic parageneses and geothermobarometric calculations indicate that the possible metamorphic peak may be higher than 900°C of temperature and around 10 kbar of pressure, within a isothermal decompression (ITD) regime.

Zircon fission track and U-Pb dating methods applied to São Paulo and Taubaté Basins located in the southeast Brazil

Zircon samples from the Cenozoic São Paulo and Taubaté Basins and Mantiqueira Mountain Range (southeast Brazil) were concomitantly dated by zircon Fission Track Method (FTM) and in situ U-Pb dating method. While FTM detrital-zircon data are ideally used to provide low-temperature information, U-Pb single detrital grain ages record the time of zircon formation in igneous or high grade metamorphic environments. This methodology may be used to study the possible sources of the basins sediments. The results suggest that the São Paulo Basin is composed of sediments from just one source, the Mantiqueira Mountain Range. On the other hand, the Taubaté Basin presents further sediment sources besides the Mantiqueira Mountain Range. © 2012 Elsevier Ltd. All rights reserved.

Datação Sm-Nd em rocha total e granada do metamorfismo granulítico da região de Tartarugal Grande, Amapá Central

O procedimento experimental do método Sm-Nd utilizado no laboratório de Geologia Isotópica Pará-Iso (Universidade Federal do Pará) é apresentado detalhadamente para poder ser utilizado como referência pelos usuários do laboratório. A datação Sm-Nd de granulitos félsicos da área de Tartarugal Grande, nordeste do Bloco Arqueano Amapá, (sudeste do Escudo das Guianas) forneceu idades isocrônicas rocha total-granada de 2017 ± 12 Ma, 1981,6 ± 2,8 Ma e 2018 ± 2,3 Ma. A análise das mesmas amostras no Laboratório de Geocronologia (Universidade de Brasília) indicou idades de 2037 ± 8,4 Ma, 1988 ± 11 Ma e 2013 ± 15 Ma, respectivamente. Esses resultados indicam que temperaturas acima de 700°C foram alcançadas pelos granulitos de Tartarugal Grande entre 2,04 - 1,98 Ga, comprovando uma idade tardi-Transamazônica para o evento de alto grau metamórfico, na região nordeste do Bloco Arqueano Amapá. As idades-modelo T_DM(Nd) entre 3,15 Ga e 2,79 Ga constituem mais um registro do evento principal de acresção crustal mesoarqueano, já identificado na porção sudeste do Escudo das Guianas.

Aprimoramento da sistemática U-Pb através do método de traços de fissão e técnicas de caracterização: termocronologia da faixa Brasília e sua correlação com a bacia do Paraná

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Constraints on the thermal evolution of the Adriatic margin during Jurassic continental break-up: U–Pb dating of rutile from the Ivrea–Verbano Zone, Italy

The Ivrea–Verbano Zone (IVZ), northern Italy, exposes an attenuated section through the Permian lower crust that records high-temperature metamorphism under lower crustal conditions and a protracted history of extension and exhumation associated partly with the Jurassic opening of the Alpine Tethys ocean. This study presents SHRIMP U–Pb geochronology of rutile from seven granulite facies metapelites from the base of the IVZ, collected from locations spanning ~35 km along the strike of Paleozoic fabrics. Rutile crystallised during Permian high-temperature metamorphism and anatexis, yet all samples give Jurassic rutile U–Pb ages that record cooling through 650–550 °C. Rutile age distributions are dominated by a peak at ~160 Ma, with a subordinate peak at ~175 Ma. Both ~160 and ~175 Ma age populations show excellent agreement between samples, indicating that the two distinctive cooling stages they record were synchronous on a regional scale. The ~175 Ma population is interpreted to record cooling in the footwall of rift-related faults and shear zones, for which widespread activity in the Lower Jurassic has been documented along the western margin of the Adriatic plate. The ~160 Ma age population postdates the activity of all known rift-related structures within the Adriatic margin, but coincides with extensive gabbroic magmatism and exhumation of sub-continental mantle to the floor of the Alpine Tethys, west of the Ivrea Zone. We propose that this ~160 Ma early post-rift age population records regional cooling following episodic heating of the distal Adriatic margin, likely related to extreme lithospheric thinning and associated advection of the asthenosphere to shallow levels. The partial preservation of the ~175 Ma age cluster suggests that the post-rift (~160 Ma) heating pulse was of short duration. The regional consistency of the data presented here, which is in contrast to many other thermochronometers in the IVZ, demonstrates the value of the rutile U–Pb technique for probing the thermal evolution of high-grade metamorphic terrains. In the IVZ, a significant decoupling between Zr-in-rutile temperatures and U–Pb ages of rutile is observed, with the two systems recording events ~120 Ma apart.