313 research outputs found

    Сульфидная система в раннепротерозойских породах чечелеевского литолого-стратиграфического уровня Кировоградского мегаблока (Украинский щит)

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    На основе минералогических, изотопных и термобарогеохимических исследований прослежена эволюция сульфидной системы от исходных метаморфогенных до гидротермально-метасоматических ассоциаций. В рамках этой эволюции проведено сопоставление изотопного состава серы магнитных и немагнитных пирротинов.На основі мінералогічних, ізотопних і термобарогеохімічних досліджень простежено еволюцію сульфідної системи від вихідних метаморфогенних до гідротермально- метасоматичних асоціацій. В межах цієї еволюції проведено порівняння ізотопного складу сірки магнітних та немагнітних піротинів.On the base of mineralogical, isotopic and thermobarogeochemical investigations the evolution of sulfide system from host metamorphic to hydrothermal-metasomatic associations was trashed. At the frames of this evolution the comparison of isotopic composition of magnetic and nonmagnetic pyrrhotite sulfur was carried out

    Local probing of coupled interfaces between two-dimensional electron and hole gases in oxide heterostructures by variable-temperature scanning tunneling spectroscopy

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    The electronic structure of an epitaxial oxide heterostructure containing two spatially separated two-dimensional conducting sheets, one electronlike (2DEG) and the other holelike (2DHG), has been investigated using variable temperature scanning tunneling spectroscopy. Heterostructures of LaAlO3/SrTiO3 bilayers on (001)-oriented SrTiO3 (STO) substrates provide the unique possibility to study the coupling between subnanometer spaced conducting interfaces. The band gap increases dramatically at low temperatures due to a blocking of the transition from the conduction band of the STO substrate to the top of the valence band of the STO capping layer. This prevents the replenishment of the depleted electrons in the capping layer from the underlying 2DEG and enables charging of the 2DHG by applying a negative sample bias voltage within the band gap region. At low temperatures the 2DHG can be probed separately with the proposed experimental geometry, although the 2DEG is located less than 1 nm belo

    Parallel electron-hole bilayer conductivity from electronic interface reconstruction

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    The perovskite SrTiO3_3-LaAlO3_3 structure has advanced to a model system to investigate the rich electronic phenomena arising at polar interfaces. Using first principles calculations and transport measurements we demonstrate that an additional SrTiO3_3 capping layer prevents structural and chemical reconstruction at the LaAlO3_3 surface and triggers the electronic reconstruction at a significantly lower LaAlO3_3 film thickness than for the uncapped systems. Combined theoretical and experimental evidence (from magnetotransport and ultraviolet photoelectron spectroscopy) suggests two spatially separated sheets with electron and hole carriers, that are as close as 1 nm.Comment: Phys. Rev. Lett., in pres

    Back-Table Fluorescence-Guided Imaging for Circumferential Resection Margin Evaluation Using Bevacizumab-800CW in Patients with Locally Advanced Rectal Cancer

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    Negative circumferential resection margins (CRM) are the cornerstone for the curative treatment of locally advanced rectal cancer (LARC). However, in up to 18.6% of patients, tumor-positive resection margins are detected on histopathology. In this proof-of-concept study, we investigated the feasibility of optical molecular imaging as a tool for evaluating the CRM directly after surgical resection to improve tumor-negative CRM rates. Methods: LARC patients treated with neoadjuvant chemoradiotherapy received an intravenous bolus injection of 4.5 mg of bevacizumab-800CW, a fluorescent tracer targeting vascular endothelial growth factor A, 2-3 d before surgery (ClinicalTrials.gov identifier: NCT01972373). First, for evaluation of the CRM status, back-table fluorescence guided imaging (FGI) of the fresh surgical resection specimens (n = 8) was performed. These results were correlated with histopathology results. Second, for determination of the sensitivity and specificity of bevacizumab-800CW for tumor detection, a mean fluorescence intensity cutoff value was determined from the formalin-fixed tissue slices (n = 42; 17 patients). Local bevacizumab-800CW accumulation was evaluated by fluorescence microscopy. Results: Back-table FGI correctly identified a tumor-positive CRM by high fluorescence intensities in 1 of 2 patients (50%) with a tumor-positive CRM. For the other patient, low fluorescence intensities were shown, although (sub)millimeter tumor deposits were present less than 1 mm from the CRM. FGI correctly identified 5 of 6 tumor-negative CRM (83%). The 1 patient with false-positive findings had a marginal negative CRM of only 1.4 mm. Receiver operating characteristic curve analysis of the fluorescence intensities of formalin-fixed tissue slices yielded an optimal mean fluorescence intensity cutoff value for tumor detection of 5,775 (sensitivity of 96.19% and specificity of 80.39%). Bevacizumab-800CW enabled a clear differentiation between tumor and normal tissue up to a microscopic level, with a tumor-to-background ratio of 4.7 +/- 2.5 (mean SD). Conclusion: In this proof-of-concept study, we showed the potential of back-table FGI for evaluating the CRM status in LARC patients. Optimization of this technique with adaptation of standard operating procedures could change perioperative decision making with regard to extending resections or applying intraoperative radiation therapy in the case of positive CRM

    Hereditary cancer registries improve the care of patients with a genetic predisposition to cancer:contributions from the Dutch Lynch syndrome registry

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    The Dutch Hereditary Cancer Registry was established in 1985 with the support of the Ministry of Health (VWS). The aims of the registry are: (1) to promote the identification of families with hereditary cancer, (2) to encourage the participation in surveillance programs of individuals at high risk, (3) to ensure the continuity of lifelong surveillance examinations, and (4) to promote research, in particular the improvement of surveillance protocols. During its early days the registry provided assistance with family investigations and the collection of medical data, and recommended surveillance when a family fulfilled specific diagnostic criteria. Since 2000 the registry has focused on family follow-up, and ensuring the quality of surveillance programs and appropriate clinical management. Since its founding, the registry has identified over 10,000 high-risk individuals with a diverse array of hereditary cancer syndromes. All were encouraged to participate in prevention programmes. The registry has published a number of studies that evaluated the outcome of surveillance protocols for colorectal cancer (CRC) in Lynch syndrome, as well as in familial colorectal cancer. In 2006, evaluation of the effect of registration and colonoscopic surveillance on the mortality rate associated with colorectal cancer (CRC) showed that the policy led to a substantial decrease in the mortality rate associated with CRC. Following discovery of MMR gene defects, the first predictive model that could select families for genetic testing was published by the Leiden group. In addition, over the years the registry has produced many cancer risk studies that have helped to develop appropriate surveillance protocols. Hereditary cancer registries in general, and the Lynch syndrome registry in particular, play an important role in improving the clinical management of affected families.</p

    Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced by multidrug resistance-associated protein 1

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    Anthranoid laxatives, belonging to the anthraquinones as do anthracyclines, possibly increase colorectal cancer risk. Anthracyclines interfere with topoisomerase II, intercalate DNA and are substrates for P-glycoprotein and multidrug resistance-associated protein 1. P-glycoprotein and multidrug resistance-associated protein 1 protect colonic epithelial cells against xenobiotics. The aim of this study was to analyse the interference of anthranoids with these natural defence mechanisms and the direct cytotoxicity of anthranoids in cancer cell lines expressing these mechanisms in varying combinations. A cytotoxicity profile of rhein, aloe emodin and danthron was established in related cell lines exhibiting different levels of topoisomerases, multidrug resistance-associated protein 1 and P-glycoprotein. Interaction of rhein with multidrug resistance-associated protein 1 was studied by carboxy fluorescein efflux and direct cytotoxicity by apoptosis induction. Rhein was less cytotoxic in the multidrug resistance-associated protein 1 overexpressing GLC4/ADR cell line compared to GLC4. Multidrug resistance-associated protein 1 inhibition with MK571 increased rhein cytotoxicity. Carboxy fluorescein efflux was blocked by rhein. No P-glycoprotein dependent rhein efflux was observed, nor was topoisomerase II responsible for reduced toxicity. Rhein induced apoptosis but did not intercalate DNA. Aloe emodin and danthron were no substrates for MDR mechanisms. Rhein is a substrate for multidrug resistance-associated protein 1 and induces apoptosis. It could therefore render the colonic epithelium sensitive to cytotoxic agents, apart from being toxic in itself
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