New Stratigraphic and Palaeogeographic Results from the Palaeozoic and Early Mesozoic of the Middle Pontides (Northern Turkey) in the Azdavay, Devrekani, Küre and Inebolu Areas: Implications for the Carboniferous-Early Cretaceous Geodynamic Evolution and Some Related Remarks to the Karakaya Oceanic Rift Basin

The Küre Complex of the Middle Pontides, northern Turkey, is not a remnant of the Palaeotethys but consists of three different units with differing geological history, the Küre Ridge Unit, the Küre Ocean Unit and the Çalça Unit. The Küre Ridge Unit consists of the Serveçay Group, a pre-Permian, low-grade metamorphic Variscan oceanic sequence, and the Sirçalik Group, a Lower and Middle Triassic shallow-water sequence of North Alpine facies and event succession which disconformably overlies the Serveçay Group. Following a hiatus, the Sirçalik Group is overlain by marginal parts of the Akgöl Group with olistoliths of local origin which were derived mainly from the Sirçalik Group. The Küre Ocean Unit consists mostly of the Akgöl Group (siliciclastic turbidites and olistostromes of the Karadagtepe Formation, which is a middle Carnian to Middle Jurassic accretionary complex from the southern, active margin of the Küre Ocean, and mainly Middle Jurassic molasse type shallow-water sandstones, siltstones and shales of an unnamed formation) and of thick oceanic basalts (Ipsinler Basalt). Tectonic slices of Middle Triassic to lower Carnian ophiolites and basalts are also present. The Karadagtepe Formation contains numerous Middle Triassic exotic olistoliths and blocks of shallow-water and predominantly slope and basinal limestones, ocean-floor deep-sea sediments (shales and radiolarites), basalts and small clasts of ophiolites or ophiolitic detritus. The Çalça Unit consists of deposits from the northern, passive margin of the Küre ocean with many Pelsonian to upper Norian Hallstatt Limestones and Rhaetian-Lower Jurassic (?Middle Jurassic) deep-water shales and marls. All three units are overlain following a period of non deposition by the Upper Jurassic Bürnük Formation (red conglomerate, sandstone) and Inalti Formation (shallow-water platform carbonates). The Küre Ridge Unit was split away from the Variscan Sakarya Continent by the opening of the Karakaya oceanic rift basin during latest Permian (Dorashamian) and became a continental splinter between the Karakaya oceanic rift basin and the Küre Ocean (opened during the late Scythian). Southward subduction began in the Küre Ocean during the middle Carnian (beginning of the Karadagtepe siliciclastic turbidites), whereas at the northern passive margin the deposition of Hallstatt Limestones continued until the latest Norian. The deposition of siliciclastic turbidites and olistostromes (Diskaya Unit) began in the entire Karakaya oceanic rift basin during the middle Carnian, and ocean basin deposits (radiolarites, pelagic limestones) and slope deposits form the passive margin (e.g., Hallstatt Limestones) are no more present in the Karakaya oceanic rift basin indicating that this basin was very narrow (only a few hundreds of kilometres). During the late Norian, the Karakaya oceanic rift basin closed, whereas subduction at the southern (active margin) of the Küre ocean continued. At the northern margin of the (Upper Triassic?) Jurassic-Lower Cretaceous Beykoz-Çaglayan turbidite basin (north of the Küre Complex) the accretionary complex of an older ocean, the Late Palaeozoic Paphlagonian Ocean, was exposed that yielded clasts in the Beykoz-Çaglayan turbidite basin. Among these clasts Carboniferous to Middle Permian (Capitanian) pelagic rocks (pelagic limestones, radiolarites) could be dated. A Middle to Late Permian southward-directed subduction is assumed for the Paphlagonian Ocean. Its closure occurred either at the end of the Permian or during the Scythian

PTPRD is homozygously deleted and epigenetically downregulated in human hepatocellular carcinomas

PTPRD (protein tyrosine phosphatase, receptor type, D) is a tumor suppressor gene, frequently inactivated through deletions or epigenetic mechanisms in several cancers with importance for global health. In this study, we provide new and functionally integrated evidence on genetic and epigenetic alterations of PTPRD gene in hepatocellular carcinomas (HCCs). Importantly, HCC is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. We used a high throughput single nucleotide polymorphism (SNP) microarray assay (Affymetrix, 10K2.0 Assay) covering the whole genome to screen an extensive panel of HCC cell lines (N=14 in total) to detect DNA copy number changes. PTPRD expression was determined in human HCCs by Q-RT-PCR and immunohistochemistry. Promoter hypermethylation was assessed by combined bisulfite restriction analysis (COBRA). DNA methyl transferase inhibitor 5-azacytidine (5-AzaC) and/or histone deacetylase inhibitor Trichostain A (TSA) were used to restore the expression. We identified homozygous deletions in Mahlavu and SNU475 cells, in the 5′UTR and coding regions, respectively. PTPRD mRNA expression was downregulated in 78.5% of cell lines and 82.6% of primary HCCs. PTPRD protein expression was also found to be lost or reduced in HCC tumor tissues. We found promoter hypermethylation in 22.2% of the paired HCC samples and restored PTPRD expression by 5-AzaC and/or TSA treatments. In conclusion, PTPRD is homozygously deleted and epigenetically downregulated in HCCs. We hypothesize PTPRD as a tumor suppressor candidate and potential cancer biomarker in human HCCs. This hypothesis is consistent with compelling evidences in other organ systems, as discussed in this article. Further functional assays in larger samples may ascertain the contribution of PTPRD to hepatocarcinogenesis in greater detail, not to forget its broader importance for diagnostic medicine and the emerging field of personalized medicine in oncology. © Copyright 2015, Mary Ann Liebert, Inc. 2015

Collaborative workspaces for pathway curation

We present a web based visual biocuration workspace, focusing on curating detailed mechanistic pathways. It was designed as a flexible platform where multiple humans, NLP and AI agents can collaborate in real-time on a common model using an event driven API. We will use this platform for exploring disruptive technologies that can scale up biocuration such as NLP, human-computer collaboration, crowd-sourcing, alternative publishing and gamification. As a first step, we are designing a pilot to include an author-curation step into the scientific publishing, where the authors of an article create formal pathway fragments representing their discovery- heavily assisted by computer agents. We envision that this "microcuration" use-case will create an excellent opportunity to integrate multiple NLP approaches and semi-automated curation. © 2016, CEUR-WS. All rights reserved

Filtering out the cosmological constant in the Palatini formalism of modified gravity

According to theoretical physics the cosmological constant (CC) is expected to be much larger in magnitude than other energy densities in the universe, which is in stark contrast to the observed Big Bang evolution. We address this old CC problem not by introducing an extremely fine-tuned counterterm, but in the context of modified gravity in the Palatini formalism. In our model the large CC term is filtered out, and it does not prevent a standard cosmological evolution. We discuss the filter effect in the epochs of radiation and matter domination as well as in the asymptotic de Sitter future. The final expansion rate can be much lower than inferred from the large CC without using a fine-tuned counterterm. Finally, we show that the CC filter works also in the Kottler (Schwarzschild-de Sitter) metric describing a black hole environment with a CC compatible to the future de Sitter cosmos.Comment: 22 pages, 1 figure, discussion extended, references added, accepted by Gen.Rel.Gra

Exploring flavor structure of supersymmetry breaking from rare B decays and unitarity triangle

We study effects of supersymmetric particles in various rare B decay processes as well as in the unitarity triangle analysis. We consider three different supersymmetric models, the minimal supergravity, SU(5) SUSY GUT with right-handed neutrinos, and the minimal supersymmetric standard model with U(2) flavor symmetry. In the SU(5) SUSY GUT with right-handed neutrinos, we consider two cases of the mass matrix of the right-handed neutrinos. We calculate direct and mixing-induced CP asymmetries in the b to s gamma decay and CP asymmetry in B_d to phi K_S as well as the B_s--anti-B_s mixing amplitude for the unitarity triangle analysis in these models. We show that large deviations are possible for the SU(5) SUSY GUT and the U(2) model. The pattern and correlations of deviations from the standard model will be useful to discriminate the different SUSY models in future B experiments.Comment: revtex4, 36 pages, 10 figure

Rationale, design and methodology of APPROACH-IS II: International study of patient-reported outcomes and frailty phenotyping in adults with congenital heart disease.

In recent years, patient-reported outcomes (PROs) have received increasing prominence in cardiovascular research and clinical care. An understanding of the variability and global experience of PROs in adults with congenital heart disease (CHD), however, is still lacking. Moreover, information on epidemiological characteristics and the frailty phenotype of older adults with CHD is minimal. The APPROACH-IS II study was established to address these knowledge gaps. This paper presents the design and methodology of APPROACH-IS II. APPROACH-IS II is a cross-sectional global multicentric study that includes Part 1 (assessing PROs) and Part 2 (investigating the frailty phenotype of older adults). With 53 participating centers, located in 32 countries across six continents, the aim is to enroll 8000 patients with CHD. In Part 1, self-report surveys are used to collect data on PROs (e.g., quality of life, perceived health, depressive symptoms, autonomy support), and explanatory variables (e.g., social support, stigma, illness identity, empowerment). In Part 2, the cognitive functioning and frailty phenotype of older adults are measured using validated assessments. APPROACH-IS II will generate a rich dataset representing the international experience of individuals in adult CHD care. The results of this project will provide a global view of PROs and the frailty phenotype of adults with CHD and will thereby address important knowledge gaps. Undoubtedly, the project will contribute to the overarching aim of improving optimal living and care provision for adults with CHD