Fault-Aware Non-Collective Communication Creation and Reparation in MPI

The increasing size of HPC architectures makes the faults' presence a more and more frequent eventuality. This issue becomes especially relevant since MPI, the de-facto standard for inter-process communication, lacks proper fault management functionalities. Past efforts produced extensions to the MPI standard that enabled fault management, including ULFM. While providing powerful tools to handle faults, it still faces limitations like the collectiveness of the repair procedure. With this paper, we overcome those limitations and achieve fault-aware non-collective communicator creation and reparation. We integrate our solution into an existing fault resiliency framework and measure the overhead introduced in the application code. The experimental campaign shows that our solution is scalable and introduces a limited overhead, and the non-collective reparation is a viable opportunity for ULFM-based applications

Effect of Argania spinosa oil extract on proliferation and Notch1 and ERK1/2 signaling of T-cell acute lymphoblastic leukemia cell lines

The Argan tree, called Argania spinosa (L.) Skeels, is a tropical plant, which belongs to the Sapotaceae family, it is exploited essentially for its fruits. The endosperm seed of the fruit constitutes a good potential source of edible oil for human consumption and is endowed with important medicinal properties such as antioxidant, antimalarial and anti-proliferative. The aim of the present work is to evaluate the anti-proliferative effect of the oil extracted from seeds of A. spinosa in T-cell acute lymphoblastic leukemia human (T-ALL) context. The activity was assessed through an in vitro test on three T-ALL cell lines: JURKAT, MOLT3 and DND41. The cytotoxicity effects of A. spinosa oil extract were checked by MTT assay and the change in the activity levels of two T-ALL proliferation-related proteins (Notch1 and ERK) was investigated by Western blot, the results demonstrate that treatment with A. spinosa oil extract at the dose of 100 μg/mL inhibited the growth of JURKAT, MOLT3 and DND41 cells, and reduced the expression levels and the activity of proliferation-related proteins such as ERK1/2 and Notch1 intracellular domain. A. spinosa oil extract could be a potential preventive and therapeutic approach recommended as anti-proliferative against leukemia

DNA damage stress: Cui prodest?

DNA is an entity shielded by mechanisms that maintain genomic stability and are essential for living cells; however, DNA is constantly subject to assaults from the environment throughout the cellular life span, making the genome susceptible to mutation and irreparable damage. Cells are prepared to mend such events through cell death as an extrema ratio to solve those threats from a multicellular perspective. However, in cells under various stress conditions, checkpoint mechanisms are activated to allow cells to have enough time to repair the damaged DNA. In yeast, entry into the cell cycle when damage is not completely repaired represents an adaptive mechanism to cope with stressful conditions. In multicellular organisms, entry into cell cycle with damaged DNA is strictly forbidden. However, in cancer development, individual cells undergo checkpoint adaptation, in which most cells die, but some survive acquiring advantageous mutations and selfishly evolve a conflictual behavior. In this review, we focus on how, in cancer development, cells rely on checkpoint adaptation to escape DNA stress and ultimately to cell death

Over the Frontier. Remote Sensing Analysis of the Roman Eastern Borderland in Mesopotamia through Declassified Satellite and Aerial Imagery

This paper discusses the spatial configuration of the Roman easternmost borderland in Mesopotamia through several case studies and, particularly, with the aid of declassified aerial and satellite imagery. Satellite pictures from the 1960s and 1970s have proved to be of incredible value for the archaeological research in the Near East, contributing to a solid advancement in the understanding of large-scale phenomena on long-term periods. This is particularly true for the so-called late periods of Mesopotamian history which – traditionally – suffer from an inexplicable lack of terrain data. Although the research has consistently improved in the las decade or so, the support of remote-sensing techniques has open new and fruitful research trajectories on the matter. I will employ legacy aerial data, CORONA and HEXAGON declassified satellite imagery and U2 aerial data to assess some case studies in the region and to provide new insights on such a contested space, now roughly comprised between northeastern Syria and northwestern Iraq

Legio: Fault Resiliency for Embarrassingly Parallel MPI Applications

Due to the increasing size of HPC machines, the fault presence is becoming an eventuality that applications must face. Natively, MPI provides no support for the execution past the detection of a fault, and this is becoming more and more constraining. With the introduction of ULFM (User Level Fault Mitigation library), it has been provided with a possible way to overtake a fault during the application execution at the cost of code modifications. ULFM is intrusive in the application and requires also a deep understanding of its recovery procedures. In this paper we propose Legio, a framework that lowers the complexity of introducing resiliency in an embarrassingly parallel MPI application. By hiding ULFM behind the MPI calls, the library is capable to expose resiliency features to the application in a transparent manner thus removing any integration effort. Upon fault, the failed nodes are discarded and the execution continues only with the non-failed ones. A hierarchical implementation of the solution has been also proposed to reduce the overhead of the repair process when scaling towards a large number of nodes. We evaluated our solutions on the Marconi100 cluster at CINECA, showing that the overhead introduced by the library is negligible and it does not limit the scalability properties of MPI. Moreover, we also integrated the solution in real-world applications to further prove its robustness by injecting faults

Fault Awareness in the MPI 4.0 Session Model

The latest version of MPI introduces new functionalities like the Session model, but it still lacks fault management mechanisms. Past efforts produced tools and MPI standard extensions to manage fault presence, including ULFM. These measures are effective against faults but do not fully support the new additions to the standard. In this paper, we combine the fault management possibilities of ULFM with the new Session model functionality introduced in version 4.0 of the standard. We focus on the communicator creation procedure, highlighting criticalities and proposing a method to circumvent them. The experimental campaign shows that the proposed solution does not significantly affect applications' execution time and scalability while better managing the insurgence of faults

The epigenetic factor BORIS/CTCFL regulates the NOTCH3 gene expression in cancer cells.

Aberrant upregulation of NOTCH3 gene plays a critical role in cancer pathogenesis. However, the underlying mechanisms are still unknown. We tested here the hypothesis that aberrant epigenetic modifications in the NOTCH3 promoter region might account for its upregulation in cancer cells. We compared DNA and histone methylation status of NOTCH3 promoter region in human normal blood cells and T cell acute lymphoblastic leukemia (T-ALL) cell lines, differentially expressing NOTCH3. We found that histone methylation, rather than DNA hypomethylation, contributes towards establishing an active chromatin status of NOTCH3 promoter in NOTCH3 overexpressing cancer cells. We discovered that the chromatin regulator protein BORIS/CTCFL plays an important role in regulating NOTCH3 gene expression. We observed that BORIS is present in T-ALL cell lines as well as in cell lines derived from several solid tumors overexpressing NOTCH3. Moreover, BORIS targets NOTCH3 promoter in cancer cells and it is able to induce and to maintain a permissive/active chromatin conformation. Importantly, the association between NOTCH3 overexpression and BORIS presence was confirmed in primary T-ALL samples from patients at the onset of the disease. Overall, our results provide novel insights into the determinants of NOTCH3 overexpression in cancer cells, by revealing a key role for BORIS as the main mediator of transcriptional deregulation of NOTCH3. Copyright © 2014 Elsevier B.V. All rights reserved

The archaeal eIF2 homologue: functional properties of an ancient translation initiation factor

The eukaryotic translation initiation factor 2 (eIF2) is pivotal for delivery of the initiator tRNA (tRNAi) to the ribosome. Here, we report the functional characterization of the archaeal homologue, a/eIF2. We have cloned the genes encoding the three subunits of a/eIF2 from the thermophilic archaeon Sulfolobus solfataricus, and have assayed the activities of the purified recombinant proteins in vitro. We demonstrate that the trimeric factor reconstituted from the recombinant polypeptides has properties similar to those of its eukaryal homologue: it interacts with GTP and Met-tRNAi, and stimulates binding of the latter to the small ribosomal subunit. However, the archaeal protein differs in some functional aspects from its eukaryal counterpart. In contrast to eIF2, a/eIF2 has similar affinities for GDP and GTP, and the β-subunit does not contribute to tRNAi binding. The detailed analysis of the complete trimer and of its isolated subunits is discussed in light of the evolutionary history of the eIF2-like proteins

Maml1 acts cooperatively with Gli proteins to regulate Sonic hedgheog signaling pathway

Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule cell progenitors (GCPs) and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma. The effects of Shh pathway are mediated by the Gli family of transcription factors, which controls the expression of a number of target genes, including Gli1. Here, we identify Mastermind-like 1 (Maml1) as a novel regulator of the Shh signaling since it interacts with Gli proteins, working as a potent transcriptional coactivator. Notably, Maml1 silencing results in a significant reduction of Gli target genes expression, with a negative impact on cell growth of NIH3T3 and Patched1−/− mouse embryonic fibroblasts (MEFs), bearing a constitutively active Shh signaling. Remarkably, Shh pathway activity results severely compromised both in MEFs and GCPs deriving from Maml1−/− mice with an impairment of GCPs proliferation and cerebellum development. Therefore Maml1−/− phenotype mimics aspects of Shh pathway deficiency, suggesting an intrinsic requirement for Maml1 in cerebellum development. The present study shows a new role for Maml1 as a component of Shh signaling, which plays a crucial role in both development and tumorigenesis