1,166 research outputs found

    Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

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    Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

    Many-core applications to online track reconstruction in HEP experiments

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    Interest in parallel architectures applied to real time selections is growing in High Energy Physics (HEP) experiments. In this paper we describe performance measurements of Graphic Processing Units (GPUs) and Intel Many Integrated Core architecture (MIC) when applied to a typical HEP online task: the selection of events based on the trajectories of charged particles. We use as benchmark a scaled-up version of the algorithm used at CDF experiment at Tevatron for online track reconstruction - the SVT algorithm - as a realistic test-case for low-latency trigger systems using new computing architectures for LHC experiment. We examine the complexity/performance trade-off in porting existing serial algorithms to many-core devices. Measurements of both data processing and data transfer latency are shown, considering different I/O strategies to/from the parallel devices.Comment: Proceedings for the 20th International Conference on Computing in High Energy and Nuclear Physics (CHEP); missing acks adde

    GPU-based Real-time Triggering in the NA62 Experiment

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    Over the last few years the GPGPU (General-Purpose computing on Graphics Processing Units) paradigm represented a remarkable development in the world of computing. Computing for High-Energy Physics is no exception: several works have demonstrated the effectiveness of the integration of GPU-based systems in high level trigger of different experiments. On the other hand the use of GPUs in the low level trigger systems, characterized by stringent real-time constraints, such as tight time budget and high throughput, poses several challenges. In this paper we focus on the low level trigger in the CERN NA62 experiment, investigating the use of real-time computing on GPUs in this synchronous system. Our approach aimed at harvesting the GPU computing power to build in real-time refined physics-related trigger primitives for the RICH detector, as the the knowledge of Cerenkov rings parameters allows to build stringent conditions for data selection at trigger level. Latencies of all components of the trigger chain have been analyzed, pointing out that networking is the most critical one. To keep the latency of data transfer task under control, we devised NaNet, an FPGA-based PCIe Network Interface Card (NIC) with GPUDirect capabilities. For the processing task, we developed specific multiple ring trigger algorithms to leverage the parallel architecture of GPUs and increase the processing throughput to keep up with the high event rate. Results obtained during the first months of 2016 NA62 run are presented and discussed

    Toll-like receptor kinetics in septic shock patients: a preliminary study.

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    The aim of this study is to evaluate some inflammatory parameter changes in septic shock patients and their possible correlation with clinical outcome, in particular when continuous veno-venous hemofiltration (CVVH) treatment is required. Considering the objective difficulty in enrolling this kind of patient, a preliminary study was initiated on seventeen septic shock patients admitted to a medical and surgical ICU. The mRNA expression of Toll-like receptor (TLR)-1, TLR-2, TLR-4, TLR-5, TLR-9, TNFalpha, IL-8 and IL-1beta was assessed, the plasmatic concentrations of IL-18, IL-2, IL-10 and TNFalpha were measured on the day of sepsis diagnosis and after 72 h. In those patients who developed acute renal failure unresponsive to medical treatment and who underwent CVVH treatment the same parameters were measured every 24 h during CVVH and after completion of the treatment. On sepsis diagnosis, gene expression of TLRs was up-regulated compared to the housekeeping gene in all the patients. After 72 h, in 35% of the patients a down-regulation of these genes was found compared to day 1, but it was not associated with a reduction of cytokine serum levels or improved clinical signs, better outcome or reduced mortality. After high volume hemofiltration treatment, cytokine serum levels and TLR expression were not significantly modified. In conclusion, considering the not numerous number of cases, from our preliminary study, we cannot certainly correlate TLR over-expression in septic shock patients with severity or outcome scores

    NaNet: a Low-Latency, Real-Time, Multi-Standard Network Interface Card with GPUDirect Features

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    While the GPGPU paradigm is widely recognized as an effective approach to high performance computing, its adoption in low-latency, real-time systems is still in its early stages. Although GPUs typically show deterministic behaviour in terms of latency in executing computational kernels as soon as data is available in their internal memories, assessment of real-time features of a standard GPGPU system needs careful characterization of all subsystems along data stream path. The networking subsystem results in being the most critical one in terms of absolute value and fluctuations of its response latency. Our envisioned solution to this issue is NaNet, a FPGA-based PCIe Network Interface Card (NIC) design featuring a configurable and extensible set of network channels with direct access through GPUDirect to NVIDIA Fermi/Kepler GPU memories. NaNet design currently supports both standard - GbE (1000BASE-T) and 10GbE (10Base-R) - and custom - 34~Gbps APElink and 2.5~Gbps deterministic latency KM3link - channels, but its modularity allows for a straightforward inclusion of other link technologies. To avoid host OS intervention on data stream and remove a possible source of jitter, the design includes a network/transport layer offload module with cycle-accurate, upper-bound latency, supporting UDP, KM3link Time Division Multiplexing and APElink protocols. After NaNet architecture description and its latency/bandwidth characterization for all supported links, two real world use cases will be presented: the GPU-based low level trigger for the RICH detector in the NA62 experiment at CERN and the on-/off-shore data link for KM3 underwater neutrino telescope

    Progress and status of APEmille

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    We report on the progress and status of the APEmille project: a SIMD parallel computer with a peak performance in the TeraFlops range which is now in an advanced development phase. We discuss the hardware and software architecture, and present some performance estimates for Lattice Gauge Theory (LGT) applications.Comment: Talk presented at LATTICE97, 3 pages, Late

    apeNEXT: A multi-TFlops Computer for Simulations in Lattice Gauge Theory

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    We present the APE (Array Processor Experiment) project for the development of dedicated parallel computers for numerical simulations in lattice gauge theories. While APEmille is a production machine in today's physics simulations at various sites in Europe, a new machine, apeNEXT, is currently being developed to provide multi-Tflops computing performance. Like previous APE machines, the new supercomputer is largely custom designed and specifically optimized for simulations of Lattice QCD.Comment: Poster at the XXIII Physics in Collisions Conference (PIC03), Zeuthen, Germany, June 2003, 3 pages, Latex. PSN FRAP15. Replaced for adding forgotten autho

    A simple method for generating full length cDNA from low abundance partial genomic clones

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    BACKGROUND: PCR amplification of target molecules involves sequence specific primers that flank the region to be amplified. While this technique is generally routine, its applicability may not be sufficient to generate a desired target molecule from two separate regions involving intron /exon boundaries. For these situations, the generation of full-length complementary DNAs from two partial genomic clones becomes necessary for the family of low abundance genes. RESULTS: The first approach we used for the isolation of full-length cDNA from two known genomic clones of Hox genes was based on fusion PCR. Here we describe a simple and efficient method of amplification for homeobox D13 (HOXD13) full length cDNA from two partial genomic clones. Specific 5' and 3' untranslated region (UTR) primer pairs and website program (primer3_www.cgv0.2) were key steps involved in this process. CONCLUSIONS: We have devised a simple, rapid and easy method for generating cDNA clone from genomic sequences. The full length HOXD13 clone (1.1 kb) generated with this technique was confirmed by sequence analysis. This simple approach can be utilized to generate full-length cDNA clones from available partial genomic sequences
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