bluuebunny/crossref_metadata_2025_split huggingface dataset:
PolyMage
Authors: Mullapudi Ravi Teja , Vasista Vinay , Bondhugula Uday 
Published: May 2015

This paper presents the design and implementation of PolyMage, a domain-specific language and compiler for image processing pipelines. An image processing pipeline can be viewed as a graph of interconnected stages which process images successively. Each stage typically performs one of point-wise, stencil, reduction or data-dependent operations on image pixels. Individual stages in a pipeline typically exhibit abundant data parallelism that can be exploited with relative ease. However, the stages also require high memory bandwidth preventing effective utilization of parallelism available on modern architectures. For applications that demand high performance, the traditional options are to use optimized libraries like OpenCV or to optimize manually. While using libraries precludes optimization across library routines, manual optimization accounting for both parallelism and locality is very tedious.
The focus of our system, PolyMage, is on automatically generating high-performance implementations of image processing pipelines expressed in a high-level declarative language. Our optimization approach primarily relies on the transformation and code generation capabilities of the polyhedral compiler framework. To the best of our knowledge, this is the first model-driven compiler for image processing pipelines that performs complex fusion, tiling, and storage optimization automatically. Experimental results on a modern multicore system show that the performance achieved by our automatic approach is up to 1.81x better than that achieved through manual tuning in Halide, a state-of-the-art language and compiler for image processing pipelines. For a camera raw image processing pipeline, our performance is comparable to that of a hand-tuned implementation.
More is Less, Less is More
Authors: Pang Jun , Dwyer Chris , Lebeck Alvin R. 
Published: May 2015

Molecular-scale Network-on-Chip (mNoC) crossbars use quantum dot LEDs as an on-chip light source, and chromophores to provide optical signal filtering for receivers. An mNoC reduces power consumption or enables scaling to larger crossbars for a reduced energy budget compared to current nanophotonic NoC crossbars. Since communication latency is reduced by using a high-radix crossbar, minimizing power consumption becomes a primary design target. Conventional Single Writer Multiple Reader (SWMR) photonic crossbar designs broadcast all packets, and incur the commensurate required power, even if only two nodes are communicating.
This paper introduces power topologies, enabled by unique capabilities of mNoC technology, to reduce overall interconnect power consumption. A power topology corresponds to the logical connectivity provided by a given power mode. Broadcast is one power mode and it consumes the maximum power. Additional power modes consume less power but allow a source to communicate with only a statically defined, potentially non-contiguous, subset of nodes. Overall interconnect power is reduced if the more frequently communicating nodes use modes that consume less power, while less frequently communicating nodes use modes that consume more power. We also investigate thread mapping techniques to fully exploit power topologies. We explore various mNoC power topologies with one, two and four power modes for a radix-256 SWMR mNoC crossbar. Our results show that the combination of power topologies and intelligent thread mapping can reduce total mNoC power by up to 51% on average for a set of 12 SPLASH benchmarks. Furthermore performance is 10% better than conventional resonator-based photonic NoCs and energy is reduced by 72%.
Asymmetric Memory Fences
Authors: Duan Yuelu , Honarmand Nima , Torrellas Josep 
Published: May 2015

There have been several recent efforts to improve the performance of fences. The most aggressive designs allow post-fence accesses to retire and complete before the fence completes. Unfortunately, such designs present implementation difficulties due to their reliance on global state and structures.
This paper's goal is to optimize both the performance and the implementability of fences. We start-off with a design like the most aggressive ones but without the global state. We call it Weak Fence or wF. Since the concurrent execution of multiple wFs can deadlock, we combine wFs with a conventional fence (i.e., Strong Fence or sF) for the less performance-critical thread(s). We call the result an Asymmetric fence group. We also propose a taxonomy of Asymmetric fence groups under TSO. Compared to past aggressive fences, Asymmetric fence groups both are substantially easier to implement and have higher average performance. The two main designs presented (WS+ and W+) speed-up workloads under TSO by an average of 13% and 21%, respectively, over conventional fences.
VARAN the Unbelievable
Authors: Hosek Petr , Cadar Cristian 
Published: May 2015

With the widespread availability of multi-core processors, running multiple diversified variants or several different versions of an application in parallel is becoming a viable approach for increasing the reliability and security of software systems. The key component of such N-version execution (NVX) systems is a runtime monitor that enables the execution of multiple versions in parallel. Unfortunately, existing monitors impose either a large performance overhead or rely on intrusive kernel-level changes. Moreover, none of the existing solutions scales well with the number of versions, since the runtime monitor acts as a performance bottleneck.
In this paper, we introduce Varan, an NVX framework that combines selective binary rewriting with a novel event-streaming architecture to significantly reduce performance overhead and scale well with the number of versions, without relying on intrusive kernel modifications.
Our evaluation shows that Varan can run NVX systems based on popular C10k network servers with only a modest performance overhead, and can be effectively used to increase software reliability using techniques such as transparent failover, live sanitization and multi-revision execution.
Enhanced MET Translation and Signaling Sustains K-Ras–Driven Proliferation under Anchorage-Independent Growth Conditions
Authors: Fujita-Sato Saori , Galeas Jacqueline , Truitt Morgan , Pitt Cameron , Urisman Anatoly , Bandyopadhyay Sourav , Ruggero Davide , McCormick Frank 
Published: May 2015

Abstract
Oncogenic K-Ras mutation occurs frequently in several types of cancers, including pancreatic and lung cancers. Tumors with K-Ras mutation are resistant to chemotherapeutic drugs as well as molecular targeting agents. Although numerous approaches are ongoing to find effective ways to treat these tumors, there are still no effective therapies for K-Ras mutant cancer patients. Here we report that K-Ras mutant cancers are more dependent on K-Ras in anchorage-independent culture conditions than in monolayer culture conditions. In seeking to determine mechanisms that contribute to the K-Ras dependency in anchorage-independent culture conditions, we discovered the involvement of Met in K-Ras–dependent, anchorage-independent cell growth. The Met signaling pathway is enhanced and plays an indispensable role in anchorage-independent growth even in cells in which Met is not amplified. Indeed, Met expression is elevated under anchorage-independent growth conditions and is regulated by K-Ras in a MAPK/ERK kinase (MEK)-dependent manner. Remarkably, in spite of a global downregulation of mRNA translation during anchorage-independent growth, we find that Met mRNA translation is specifically enhanced under these conditions. Importantly, ectopic expression of an active Met mutant rescues K-Ras ablation-derived growth suppression, indicating that K-Ras–mediated Met expression drives “K-Ras addiction” in anchorage-independent conditions. Our results indicate that enhanced Met expression and signaling is essential for anchorage-independent growth of K-Ras mutant cancer cells and suggests that pharmacological inhibitors of Met could be effective for K-Ras mutant tumor patients. Cancer Res; 75(14); 2851–62. ©2015 AACR.
Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer
Authors: Lemnrau Alina , Brook Mark N. , Fletcher Olivia , Coulson Penny , Tomczyk Katarzyna , Jones Michael , Ashworth Alan , Swerdlow Anthony , Orr Nick , Garcia-Closas Montserrat 
Published: May 2015

Abstract
Increased mitochondrial DNA (mtDNA) copy number in peripheral blood cells (PBC) has been associated with the risk of developing several tumor types. Here we evaluate sources of variation of this biomarker and its association with breast cancer risk in a prospective cohort study. mtDNA copy number was measured using quantitative real-time PCR on PBC DNA samples from participants in the UK-based Breakthrough Generations Study. Temporal and assay variation was evaluated in a serial study of 91 women, with two blood samples collected approximately 6-years apart. Then, associations with breast cancer risk factors and risk were evaluated in 1,108 cases and 1,099 controls using a nested case–control design. In the serial study, mtDNA copy number showed low assay variation but large temporal variation [assay intraclass correlation coefficient (ICC), 79.3%–87.9%; temporal ICC, 38.3%). Higher mtDNA copy number was significantly associated with younger age at blood collection, being premenopausal, having an older age at menopause, and never taking HRT, both in cases and controls. Based on measurements in a single blood sample taken on average 6 years before diagnosis, higher mtDNA copy number was associated with increased breast cancer risk [OR (95% CI) for highest versus lowest quartile, 1.37 (1.02–1.83); P trend = 0.007]. In conclusion, mtDNA copy number is associated with breast cancer risk and represents a promising biomarker for risk assessment. The relatively large temporal variation should be taken into account in future analyses. Cancer Res; 75(14); 2844–50. ©2015 AACR.
Breast Cancer Cell–Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes
Authors: Ghirelli Cristina , Reyal Fabien , Jeanmougin Marine , Zollinger Raphaël , Sirven Philémon , Michea Paula , Caux Christophe , Bendriss-Vermare Nathalie , Donnadieu Marie-Hélène , Caly Martial , Fourchotte Virginie , Vincent-Salomon Anne , Sigal-Zafrani Brigitte , Sastre-Garau Xavier , Soumelis Vassili 
Published: May 2015

AbstractReciprocal interactions between tumor cells and their microenvironment vitally impact tumor progression. In this study, we show that GM-CSF produced by primary breast tumor cells induced the activation of plasmacytoid predendritic cells (pDC), a cell type critical to anti-viral immunity. pDC that expressed the GM-CSF receptor were increased in breast tumors compared with noninvolved adjacent breast tissue. Tumor-activated pDC acquired naïve CD4+ T-cell stimulatory capacity and promoted a regulatory Th2 response. Finally, the concomitant increase of GM-CSF and pDC was significantly associated with relatively more aggressive breast cancer subtypes. Our results characterize the first tumor-derived factor that can activate pDC to promote a regulatory Th2 response, with implications for therapeutic targeting of a tumor-immune axis of growing recognition in its significance to cancer. Cancer Res; 75(14); 2775–87. ©2015 AACR.
Targeting Pancreatic Cancer Metastasis by Inhibition of Vav1, a Driver of Tumor Cell Invasion
Authors: Razidlo Gina L. , Magnine Christopher , Sletten Arthur C. , Hurley Rachel M. , Almada Luciana L. , Fernandez-Zapico Martin E. , Ji Baoan , McNiven Mark A. 
Published: May 2015

Abstract
Pancreatic cancer, one of the most lethal forms of human cancer, is largely resistant to many conventional chemotherapeutic agents. Although many therapeutic approaches focus on tumor growth, metastasis is a primary factor contributing to lethality. Therefore, novel therapies to target metastatic invasion could prevent tumor spread and recurrence resulting from local and distant metastasis. The protein Vav1 is aberrantly expressed in more than half of pancreatic cancers. Its expression promotes activation of Rac and Cdc42 and leads to enhanced invasion and migration, as well as increased tumor cell survival and proliferation, suggesting that Vav1 could be a potent therapeutic target for pancreatic cancer. The purine analogue azathioprine, well known for its function as an anti-inflammatory compound, was recently shown to function by inhibiting Vav1 signaling in immune cells. We therefore hypothesized that azathioprine could also inhibit Vav1 in pancreatic tumor cells to reduce its proinvasive functions. Indeed, we have found that treatment of cultured pancreatic tumor cells with azathioprine inhibited Vav1-dependent invasive cell migration and matrix degradation, through inhibition of Rac and Cdc42 signaling. Furthermore, azathioprine treatment decreased metastasis in both xenograft and genetic mouse models of pancreatic cancer. Strikingly, metastasis was dramatically reduced in Vav1-expressing tumors arising from p48Cre/+, KrasG12D/+, p53F/+ mice. These inhibitory effects were mediated through Vav1, as Vav1-negative cell lines and tumors were largely resistant to azathioprine treatment. These findings demonstrate that azathioprine and related compounds could be potent antimetastatic agents for Vav1-positive pancreatic tumors. Cancer Res; 75(14); 2907–15. ©2015 AACR.
Pharmacological Inhibition of β3 Integrin Reduces the Inflammatory Toxicities Caused by Oncolytic Adenovirus without Compromising Anticancer Activity
Authors: Browne Ashley , Tookman Laura A. , Ingemarsdotter Carin K. , Bouwman Russell D. , Pirlo Katrina , Wang Yaohe , McNeish Iain A. , Lockley Michelle 
Published: May 2015

Abstract
Adenoviruses have been clinically tested as anticancer therapies but their utility has been severely limited by rapid, systemic cytokine release and consequent inflammatory toxicity. Here, we describe a new approach to tackling these dangerous side effects. Using human ovarian cancer cell lines as well as malignant epithelial cells harvested from the ascites of women with ovarian cancer, we show that tumor cells do not produce cytokines in the first 24 hours following in vitro infection with the oncolytic adenovirus dl922-947. In contrast, dl922-947 does induce inflammatory cytokines at early time points following intraperitoneal delivery in mice with human ovarian cancer intraperitoneal xenografts. In these animals, cytokines originate predominantly in murine tissues, especially in macrophage-rich organs such as the spleen. We use a nonreplicating adenovirus to confirm that early cytokine production is independent of adenoviral replication. Using β3 integrin knockout mice injected intraperitoneally with dl922-947 and β3 null murine peritoneal macrophages, we confirm a role for macrophage cell surface β3 integrin in this dl922-947–induced inflammation. We present new evidence that co-administration of a cyclic RGD-mimetic–specific inhibitor of β3 integrin significantly attenuates the cytokine release and inflammatory hepatic toxicity induced by dl922-947 in an intraperitoneal murine model of ovarian cancer. Importantly, we find no evidence that β3 inhibition compromises viral infectivity and oncolysis in vitro or anticancer efficacy in vivo. By enabling safe, systemic delivery of replicating adenoviruses, this novel approach could have a major impact on the future development of these effective anticancer agents. Cancer Res; 75(14); 2811–21. ©2015 AACR.
Therapeutic Targeting of Anaplastic Lymphoma Kinase in Lung Cancer: A Paradigm for Precision Cancer Medicine
Authors: Katayama Ryohei , Lovly Christine M. , Shaw Alice T. 
Published: May 2015

Abstract
The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase was initially discovered as a component of the fusion protein nucleophosmin (NPM)–ALK in anaplastic large-cell lymphoma (ALCL). Genomic alterations in ALK, including rearrangements, point mutations, and genomic amplification, have now been identified in several malignancies, including lymphoma, non–small cell lung cancer (NSCLC), neuroblastoma, inflammatory myofibroblastic tumor, and others. Importantly, ALK serves as a validated therapeutic target in these diseases. Several ALK tyrosine kinase inhibitors (TKI), including crizotinib, ceritinib, and alectinib, have been developed, and some of them have already been approved for clinical use. These ALK inhibitors have all shown remarkable clinical outcomes in ALK-rearranged NSCLC. Unfortunately, as is the case for other kinase inhibitors in clinical use, sensitive tumors inevitably relapse due to acquired resistance. This review focuses on the discovery, function, and therapeutic targeting of ALK, with a particular focus on ALK-rearranged NSCLC. Clin Cancer Res; 21(10); 2227–35. ©2015 AACR.
See all articles in this CCR Focus section, “Progress in Lung Cancer.”
PHLPP2 Downregulation Contributes to Lung Carcinogenesis Following B[a]P/B[a]PDE Exposure
Authors: Huang Haishan , Pan Xiaofu , Jin Honglei , Li Yang , Zhang Lin , Yang Caili , Liu Pei , Liu Ya , Chen Lili , Li Jingxia , Zhu Junlan , Zeng Xingruo , Fu Kai , Chen Guorong , Gao Jimin , Huang Chuanshu 
Published: May 2015

Abstract
Purpose: The carcinogenic capacity of B[a]P/B[a]PDE is supported by epidemiologic studies. However, the molecular mechanisms responsible for B[a]P/B[a]PDE-caused lung cancer have not been well investigated. We evaluated here the role of novel target PHLPP2 in lung inflammation and carcinogenesis upon B[a]P/B[a]PDE exposure.
Experimental Design: We used the Western blotting, RT-PCR, [35S]methionine pulse and immunohistochemistry staining to determine PHLPP2 downregulation following B[a]P/B[a]PDE exposure. Both B[a]PDE-induced Beas-2B cell transformation model and B[a]P-caused mouse lung cancer model were used to elucidate the mechanisms leading to PHLPP2 downregulation and lung carcinogenesis. The important findings were also extended to in vivo human studies.
Results: We found that B[a]P/B[a]PDE exposure downregulated PHLPP2 expression in human lung epithelial cells in vitro and in mouse lung tissues in vivo. The ectopic expression of PHLPP2 dramatically inhibited cell transformation upon B[a]PDE exposure. Mechanistic studies showed that miR-205 induction was crucial for inhibition of PHLPP2 protein translation by targeting PHLPP2-3′-UTR. Interestingly, PHLPP2 expression was inversely associated with tumor necrosis factor alpha (TNFα) expression, with low PHLPP2 and high TNFα expression in lung cancer tissues compared with the paired adjacent normal lung tissues. Additional studies revealed that PHLPP2 exhibited its antitumorigenic effect of B[a]P/B[a]PDE through the repression of inflammatory TNFα transcription.
Conclusions: Our studies not only first time identify PHLPP2 downregulation by lung carcinogen B[a]P/B[a]PDE, but also elucidate a novel molecular mechanisms underlying lung inflammation and carcinogenesis upon B[a]P/B[a]PDE exposure. Clin Cancer Res; 21(16); 3783–93. ©2015 AACR.
Small Cell Lung Cancer: Will Recent Progress Lead to Improved Outcomes?
Authors: Pietanza M. Catherine , Byers Lauren Averett , Minna John D. , Rudin Charles M. 
Published: May 2015

Abstract
Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with a unique natural history characterized by a short doubling time, high growth fraction, and early development of widespread metastases. Although a chemotherapy- and radiation-sensitive disease, SCLC typically recurs rapidly after primary treatment, with only 6% of patients surviving 5 years from diagnosis. This disease has been notable for the absence of major improvements in its treatment: Nearly four decades after the introduction of a platinum–etoposide doublet, therapeutic options have remained virtually unchanged, with correspondingly little improvement in survival rates. Here, we summarize specific barriers and challenges inherent to SCLC research and care that have limited progress in novel therapeutic development to date. We discuss recent progress in basic and translational research, especially in the development of mouse models, which will provide insights into the patterns of metastasis and resistance in SCLC. Opportunities in clinical research aimed at exploiting SCLC biology are reviewed, with an emphasis on ongoing trials. SCLC has been described as a recalcitrant cancer, for which there is an urgent need for accelerated progress. The NCI convened a panel of laboratory and clinical investigators interested in SCLC with a goal of defining consensus recommendations to accelerate progress in the treatment of SCLC, which we summarize here. Clin Cancer Res; 21(10); 2244–55. ©2015 AACR.
See all articles in this CCR Focus section, “Progress in Lung Cancer.”
EGFR: The Paradigm of an Oncogene-Driven Lung Cancer
Authors: Riely Gregory J. , Yu Helena A. 
Published: May 2015

Abstract
Somatic, activating mutations in EGFR identify a significant minority of patients with non–small cell lung cancer (NSCLC). Although these mutations are associated with an approximately 70% response rate to some EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, and afatinib), patients develop resistance (i.e., “acquired resistance”) after a median of 9 to 12 months. In patients with clinical acquired resistance, repeat biopsy of tumors has identified a number of relevant mechanisms of resistance, but by far the most frequent event is the acquisition of EGFR T790M, a mutation in the “gatekeeper” residue that confers resistance to gefitinib, erlotinib, and afatinib. This emphasizes the critical dependence upon EGFR signaling for some tumors, a property that has been exploited therapeutically. Dual EGFR blockade using afatinib and cetuximab led to a 29% radiographic response rate. More recently, drugs that target EGFR T790M (e.g., rociletinib, AZD9291, and others) have entered clinical trials, with impressive results observed in phase I clinical trials. The development of these newer drugs, with efficacy after resistance to first-line EGFR tyrosine kinase inhibitor, has led to exploration of these strategies in multiple disease settings: at resistance, in the first line, and in adjuvant treatment of those with completely resected early-stage disease who would otherwise die of recurrent/metastatic disease. This example of translational research that identifies mechanisms of resistance to first-generation drugs, and then targets those mechanisms yielding clinical benefit, is a paradigm for how targeted therapies can be developed. Clin Cancer Res; 21(10); 2221–6. ©2015 AACR.
See all articles in this CCR Focus section, “Progress in Lung Cancer.”