Recent advances and open challenges in percolation

Araú,jo, N.,Grassberger, P.,Kahng, B.,Schrenk, K. J.,Ziff, R. M. SPRINGER 2014 The European physical journal. ST, Special topics Vol.223 No.11

BACH: Grand challenge on breast cancer histology images

Aresta, Guilherme,Araú,jo, Teresa,Kwok, Scotty,Chennamsetty, Sai Saketh,Safwan, Mohammed,Alex, Varghese,Marami, Bahram,Prastawa, Marcel,Chan, Monica,Donovan, Michael,Fernandez, Gerardo,Zeineh, J Elsevier 2019 Medical image analysis Vol.56 No.-

<P><B>Abstract</B></P> <P>Breast cancer is the most common invasive cancer in women, affecting more than 10% of women worldwide. Microscopic analysis of a biopsy remains one of the most important methods to diagnose the type of breast cancer. This requires specialized analysis by pathologists, in a task that i) is highly time- and cost-consuming and ii) often leads to nonconsensual results. The relevance and potential of automatic classification algorithms using hematoxylin-eosin stained histopathological images has already been demonstrated, but the reported results are still sub-optimal for clinical use. With the goal of advancing the state-of-the-art in automatic classification, the Grand Challenge on BreAst Cancer Histology images (BACH) was organized in conjunction with the 15th International Conference on Image Analysis and Recognition (ICIAR 2018). BACH aimed at the classification and localization of clinically relevant histopathological classes in microscopy and whole-slide images from a large annotated dataset, specifically compiled and made publicly available for the challenge. Following a positive response from the scientific community, a total of 64 submissions, out of 677 registrations, effectively entered the competition. The submitted algorithms improved the state-of-the-art in automatic classification of breast cancer with microscopy images to an accuracy of 87%. Convolutional neuronal networks were the most successful methodology in the BACH challenge. Detailed analysis of the collective results allowed the identification of remaining challenges in the field and recommendations for future developments. The BACH dataset remains publicly available as to promote further improvements to the field of automatic classification in digital pathology.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The BACH challenge was organized to push forward methods for automatic classification of breast cancer biopsies using clinical hematoxylin-eosin stained histopathological images. </LI> <LI> A large public dataset, composed of 400 microscopy images and 30 whole-slide images, was specifically compiled for the BACH challenge. </LI> <LI> A total of 64 methods were submitted, out of 677 registration, and a detailed comparative analysis was carried out for the methods with higher accuracy scores. </LI> <LI> Several submitted algorithms performed better than the state-of-the-art in terms of accuracy (top score of 87%). </LI> <LI> Convolutional neural networks dominated the submissions, and was the method of choice in the algorithm that won the challenge. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Human primordial germ cell commitment <i>in vitro</i> associates with a unique PRDM14 expression profile

Sugawa, Fumihiro,Araú,zo-Bravo, Marcos J,Yoon, Juyong,Kim, Kee-Pyo,Aramaki, Shinya,Wu, Guangming,Stehling, Martin,Psathaki, Olympia E,Hü,bner, Karin,Schö,ler, Hans R BlackWell Publishing Ltd 2015 The EMBO journal Vol.34 No.8

<P>Primordial germ cells (PGCs) develop only into sperm and oocytes <I>in vivo</I>. The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of <I>in vitro</I> models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre-migratory PGC-like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm-like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of <I>de novo</I> DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC-derived gametes for reproductive medicine.</P>

Reactivation of the inactive X chromosome and post-transcriptional reprogramming of <i>Xist</i> in iPSCs

Kim, Jong Soo,Choi, Hyun Woo,Araú,zo-Bravo, Marcos J.,Schö,ler, Hans R.,Do, Jeong Tae The Company of Biologists Ltd. 2015 Journal of cell science Vol.128 No.1

<P>Direct reprogramming of somatic cells to pluripotent stem cells entails the obliteration of somatic cell memory and the reestablishment of epigenetic events. Induced pluripotent stem cells (iPSCs) have been created by reprogramming somatic cells through the transduction of reprogramming factors. During cell reprogramming, female somatic cells must overcome at least one more barrier than male somatic cells in order to enter a pluripotent state, as they must reactivate an inactive X chromosome (Xi). In this study, we investigated whether the sex of somatic cells affects reprogramming efficiency, differentiation potential and the post-transcriptional processing of <I>Xist</I> RNA after reprogramming. There were no differences between male and female iPSCs with respect to reprogramming efficiency or their differentiation potential <I>in vivo</I>. However, reactivating Xi took longer than reactivating pluripotency-related genes. We also found that direct reprogramming leads to gender-appropriate post-transcriptional reprogramming – like male embryonic stem cells (ESCs), male iPSCs expressed only the long <I>Xist</I> isoform, whereas female iPSCs, like female ESCs, expressed both the long and short isoforms.</P>

The Amazon Tall Tower Observatory (ATTO): overview of pilot measurements on ecosystem ecology, meteorology, trace gases, and aerosols

Andreae, M. O.,Acevedo, O. C.,Araù,jo, A.,Artaxo, P.,Barbosa, C. G. G.,Barbosa, H. M. J.,Brito, J.,Carbone, S.,Chi, X.,Cintra, B. B. L.,da Silva, N. F.,Dias, N. L.,Dias-J&uacute,nior, C. Q.,Dita Copernicus GmbH 2015 Atmospheric Chemistry and Physics Vol.15 No.18

<P>Abstract. The Amazon Basin plays key roles in the carbon and water cycles, climate change, atmospheric chemistry, and biodiversity. It has already been changed significantly by human activities, and more pervasive change is expected to occur in the coming decades. It is therefore essential to establish long-term measurement sites that provide a baseline record of present-day climatic, biogeochemical, and atmospheric conditions and that will be operated over coming decades to monitor change in the Amazon region, as human perturbations increase in the future. The Amazon Tall Tower Observatory (ATTO) has been set up in a pristine rain forest region in the central Amazon Basin, about 150 km northeast of the city of Manaus. Two 80 m towers have been operated at the site since 2012, and a 325 m tower is nearing completion in mid-2015. An ecological survey including a biodiversity assessment has been conducted in the forest region surrounding the site. Measurements of micrometeorological and atmospheric chemical variables were initiated in 2012, and their range has continued to broaden over the last few years. The meteorological and micrometeorological measurements include temperature and wind profiles, precipitation, water and energy fluxes, turbulence components, soil temperature profiles and soil heat fluxes, radiation fluxes, and visibility. A tree has been instrumented to measure stem profiles of temperature, light intensity, and water content in cryptogamic covers. The trace gas measurements comprise continuous monitoring of carbon dioxide, carbon monoxide, methane, and ozone at five to eight different heights, complemented by a variety of additional species measured during intensive campaigns (e.g., VOC, NO, NO2, and OH reactivity). Aerosol optical, microphysical, and chemical measurements are being made above the canopy as well as in the canopy space. They include aerosol light scattering and absorption, fluorescence, number and volume size distributions, chemical composition, cloud condensation nuclei (CCN) concentrations, and hygroscopicity. In this paper, we discuss the scientific context of the ATTO observatory and present an overview of results from ecological, meteorological, and chemical pilot studies at the ATTO site. </P>

Oct4‐induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model

Kim, Jeong Beom,Lee, Hyunah,Araú,zo‐,Bravo, Marcos J,Hwang, Kyujin,Nam, Donggyu,Park, Myung Rae,Zaehres, Holm,Park, Kook In,Lee, Seok‐,Jin EMBO 2015 The EMBO journal Vol.34 No.23

<P>The generation of patient-specific oligodendrocyte progenitor cells (OPCs) holds great potential as an expandable cell source for cell replacement therapy as well as drug screening in spinal cord injury or demyelinating diseases. Here, we demonstrate that induced OPCs (iOPCs) can be directly derived from adult mouse fibroblasts by Oct4-mediated direct reprogramming, using anchorage-independent growth to ensure high purity. Homogeneous iOPCs exhibit typical small-bipolar morphology, maintain their self-renewal capacity and OPC marker expression for more than 31 passages, share high similarity in the global gene expression profile to wild-type OPCs, and give rise to mature oligodendrocytes and astrocytes in vitro and in vivo. Notably, transplanted iOPCs contribute to functional recovery in a spinal cord injury (SCI) model without tumor formation. This study provides a simple strategy to generate functional self-renewing iOPCs and yields insights for the in-depth study of demyelination and regenerative medicine.</P>

Direct conversion of mouse fibroblasts into induced neural stem cells

Kim, Sung Min,Flaßkamp, Hannah,Hermann, Andreas,Araú,zo-Bravo, Marcos Jes&uacute,s,Lee, Seung Chan,Lee, Sung Ho,Seo, Eun Hye,Lee, Seung Hyun,Storch, Alexander,Lee, Hoon Taek,Schö,ler, Hans R Nature Publishing Group, a division of Macmillan P 2014 Nature protocols Vol.9 No.4

Terminally differentiated cells can be directly converted into different types of somatic cells by using defined factors, thus circumventing the pluripotent state. However, low reprogramming efficiency, along with the absence of proliferation of some somatic cell types, makes it difficult to generate large numbers of cells with this method. Here we describe a protocol to directly convert mouse fibroblasts into self-renewing induced neural stem cells (iNSCs) that can be expanded in vitro, thereby overcoming the limitations associated with low reprogramming efficiency. The four transcription factors required for direct conversion into iNSCs (Sox2, Klf4, Myc (also known as c-Myc) and Pou3f4 (also known as Brn4)) do not generate a pluripotent cell state, and thus the risk for tumor formation after transplantation is reduced. By following the current protocol, iNSCs are observed 4–5 weeks after transduction. Two additional months are required to establish clonal iNSC cell lines that exhibit retroviral transgene silencing and that differentiate into neurons, astrocytes and oligodendrocytes.

Direct reprogramming of human neural stem cells by OCT4

Kim, Jeong Beom,Greber, Boris,Araú,zo-Bravo, Marcos J.,Meyer, Johann,Park, Kook In,Zaehres, Holm,Schö,ler, Hans R. Macmillan Publishers Limited. All rights reserved 2009 Nature Vol.461 No.7264

Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors (OCT4 (also called POU5F1), SOX2, c-Myc and KLF4). We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells. Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.

Final report on CCQM-K125: elements in infant formula

Merrick, J,Saxby, D,Dutra, E S,Sena, R C,Araú,jo, T O,Almeida, M D,Yang, L,Pihillagawa, I G,Mester, Z,Sandoval, S,Wei, C,Castillo, M E D,Oster, C,Fisicaro, P,Rienitz, O,Pape, C,Schulz, U,Jä BUREAU INTERNATIONAL DES POIDS ET MESURES 2017 METROLOGIA -BERLIN- Vol.54 No.1

Identification of radiopure titanium for the LZ dark matter experiment and future rare event searches

Akerib, D.S.,Akerlof, C.W.,Akimov, D.Yu.,Alsum, S.K.,Araú,jo, H.M.,Arnquist, I.J.,Arthurs, M.,Bai, X.,Bailey, A.J.,Balajthy, J.,Balashov, S.,Barry, M.J.,Belle, J.,Beltrame, P.,Benson, T.,Bernard North-Holland 2017 Astroparticle physics Vol.96 No.-

<P>The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a detector containing a total of 10 tonnes of liquid xenon within a double -vessel cryostat. The large mass and proximity of the cryostat to the active detector volume demand the use of material with extremely low intrinsic radioactivity. We report on the radioassay campaign conducted to identify suitable metals, the determination of factors limiting radiopure production, and the selection of titanium for construction of the LZ cryostat and other detector components. This titanium has been measured with activities of U-238(e) < 1.6 mBq/kg, U-238(I) < 0.09 mBq/kg, Th-232(e) = 0.28 +/- 0.03 mBq/kg, Th-232(I) = 0.25 +/- 0.02 mBq/kg, K-40 <0.54 mBq/kg, and (60) Co <0.02 mBq/kg (68% CL). Such low intrinsic activities, which are some of the lowest ever reported for titanium, enable its use for future dark matter and other rare event searches. Monte Carlo simulations have been performed to assess the expected background contribution from the LZ cryostat with this radioactivity. In 1,000 days of WIMP search exposure of a 5.6-tonne fiducial mass, the cryostat will contribute only a mean background of 0.160 +/- 0.001(stat) +/- 0.030(sys) counts. (C) 2017 Elsevier B.V. All rights reserved.</P>